济泰片药效物质基础及药代动力学研究
|
摘要
济泰片来源于清代道光、同治年间独创的戒断鸦片毒瘾的秘方，已被国家食品药品监督管理局（SFDA）批准可用于阿片类药物成瘾的脱毒治疗。济泰片由十五味药材（延胡索、丹参、当归、川芎、桃仁（炒）、红花、附子（制）、人参、肉桂、干姜、豆蔻、洋金花、沉香、木香和珍珠粉）以一定比例按君、臣、佐、使配伍而成。其中延胡索、丹参为君药，起到活血行气、止痛安神的作用；人参、川芎、当归、附子（制）等共为臣药，珍珠粉为佐药，洋金花为使药。临床研究表明，济泰片在戒毒治疗过程中，可显著改善和缓解脱毒戒断症状，且能显著提高患者机体免疫功能，加速患者身体戒断后的康复进程。虽然济泰片的临床疗效显著，但其发挥作用的主要物质、作用机制及其本身的质量控制标准的研究尚存在较大差距。“多成分、多靶点、多途径的整合作用”是中药复方治疗疾病的主要特点。济泰片的组成化学成分尚不清楚，体内作用的物质基础尚不明确以及药效物质基础体内作用的规律尚未阐明，这些基础研究的欠缺，无法为济泰片临床疗效提供科学依据，从而限制了济泰片的产业化与国际化。
本研究选择疗效确切的戒毒中药“济泰片”为研究对象，综合运用各种创新理论及先进的技术手段，从济泰片中主要化学成分、入血成分及入脑成分的识别等几个方面阐明济泰片药效物质基础；同时，对其药效物质基础的体内动态变化过程进行研究，为济泰片的临床药物监测和用药安全提供科学依据。具体研究内容如下：
首先，采用高效液相色谱串联二极管阵列检测器/电喷雾质谱法（HPLCDAD/ESIMS/MS）对济泰片中主要化学成分进行全面系统的表征。在对标准品母离子碎片离子的裂解规律进行分析基础上，通过对图谱中各化合物的保留时间，紫外（UV）和质谱图谱与标准品及相关文献比较，最终共鉴定了济泰片中包括生物碱类、酚酸类、丹参酮类、黄酮类、氰苷类、人参皂苷类、2[2苯乙基]色原酮类、苯酞内酯类及姜酚类化合物在内的101个化学成分，并对九类化合物的特征性裂解规律进行了总结和分析研究。在正离子模式条件下，莨菪类生物碱的裂解规律主要表现为中性丢失C9H10O3和C9H8O2单元。氰苷类化合物主要表现为中性丢失苯乙醇腈单元。卓鎓离子与C4H2O单元是2[2苯乙基]色原酮裂解中的特征性碎片，其形成过程主要为C环的RDA裂解。本研究首次对济泰片的化学成分进行了系统整体研究，建立的方法可以快速、有效地确定济泰片中主要化学成分，为济泰片的质量评价和药效物质基础研究提供大量化学信息和有力的技术支持。
在对济泰片中化学成分全面定性的基础上，本研究利用“血清药物化学理论”结合HPLCDAD/ESIMS/MS技术对济泰片入血成分进行了定性分析。SD大鼠灌胃给予济泰片1h后，肝门静脉取血，高速离心取上清。血清样品经甲醇沉淀后进行LC-MS分析。采用Waters XTerra C18色谱柱，以乙腈-水（0.1%甲酸）梯度洗脱，在正负离子模式下分别采集其质谱信息。通过综合比较分析济泰片提取液、给药大鼠血浆及空白大鼠血浆的提取离子流色谱图，并与标准品及文献数据比对，首次鉴定了济泰片中26个原型入血成分及5个代谢产物，包括6个人参皂苷类，5个生物碱类，5个苯酞内酯类，3个酚酸类，2个丹参酮类，2个氰苷类，2个姜酚类及1个查耳酮类化合物，代谢产物分别是延胡索乙素葡萄糖醛酸结合物、乙酰基丹参素、6-姜酚葡萄糖醛酸结合物、氢化丹参酮ⅡA葡萄糖醛酸结合物、氢化去氢丹参酮IIA的葡萄糖醛酸结合物。本研究首次建立了一种快速筛选大鼠口服济泰片后入血成分的整体方法，并且本研究检测的部分入血成分与相关戒毒活性的报道一致。该方法的建立不仅有助于阐释济泰片的入血成分，而且为济泰片药代动力学研究提供标志性化合物。
济泰片主要用于阿片成瘾的脱毒治疗，其作用的靶部位主要为中枢神经系统，本章采用脑脊液药物化学的理论与方法，结合快速液相色谱串联四级杆飞行时间质谱（RRLC-Q-TOF-MS/MS）技术对大鼠灌服济泰片后入脑成分进行了全面的定性分析。通过比较空白脑脊液、给药脑脊液及济泰片提取液中化学成分的差异，首次鉴定了包括生物碱类和苯酞内酯类在内的11个原型成分和3个代谢产物。同时采用快速液相色谱串联三重四级杆质谱（RRLC-QqQ-MS/MS）技术对已鉴定的部分化合物进行目标性检测，并定量了给药大鼠脑脊液中的6个成分，各成分的含量分别为：东莨菪碱1.678ng/mL，四氢小檗碱0.024ng/mL，四氢黄连碱0.014ng/mL，原阿片碱0.162ng/mL，延胡索乙素0.587ng/mL及延胡索甲素0.051ng/mL。结果表明，生物碱类和苯酞内酯类成分为济泰片作用于中枢神经系统的主要活性成分，与相关文献报道一致。本研究建立了一种快速、灵敏、准确检测中药复方体内的极微量成分的方法，为中药复方药效物质基础研究提供有力的技术支持，筛选到的目标成分可以作为作用机制研究的标志性成分。
在前述研究基础上，本章对济泰片的主要成分体内药代动力学行为进行了探讨。SD大鼠经灌胃给予济泰片15g/kg大鼠体重，于24h内采集不同时间点大鼠血浆。分别定量血浆中的四个生物碱（四氢黄连碱、四氢小檗碱、延胡索乙素及延胡索甲素）及六个酚酸类（丹参素、阿魏酸、丹酚酸A、丹酚酸B、苦杏仁苷及羟基红花色素A）化合物。血浆样品经乙腈沉淀蛋白预处理，以药根碱和没食子酸作为内标，采用亚微米粒径（1.8μm）分析柱结合RRLC-QqQ-MS/MS的多反应监测模式，分别在正离子模式下对血浆中叔铵型生物碱，与负离子模式下血浆中酚酸类成分进行监测。针对上述不同类型化合物分别采用不同的分析柱与质谱采集模式，通过对样品前处理条件、液相条件及质谱条件的优化，最终分别实现正离子模式下单针8min对血浆中4个生物碱的监测，及负离子模式下单针7min对其余成分的监测。四氢黄连碱、四氢小檗碱、延胡索乙素及延胡索甲素的最低检测限分别为2.0ng/mL、0.2ng/mL、1.0ng/mL及0.4ng/mL，而苦杏仁苷、丹参素、阿魏酸、羟基红花色素A、丹酚酸A及丹酚酸B的最低检测限分别为7.0ng/mL、2.0ng/mL、4.0ng/mL、1.0ng/mL、2.0ng/mL及4.0ng/mL。目标分析物的平均回收率范围从85.51%-93.99%，日内和日间精密度均处于1.21-4.73%的范围内。其最低定量限、精确度、准确度、回收率与基质效应均满足FDA对生物样本分析的要求。研究发现四种生物碱虽然具有相似的结构，但其体内药代动力学参数却表现出明显的不同，但都出现双峰现象。丹参素、阿魏酸、丹酚酸A及丹酚酸B的药代动力学参数中可看出各化合物在吸收和消除行为中均存在明显差异，这可能与化合物不同的理化性质及复方中化学成分相互作用相关。
Jitai tablets (JTT), an important TCM prescription in treating opiate addiction sinceQing dynasty, has been proved to be very safe and effective in the inhibition of protractedwith-drawal symptoms with less harmful side effects, which have been already approvedfor the treatment of opiate addiction by the Chinese State Food and Drug Administration(SFDA). JTT is prepared from fifteen medicinal materials, including Rhizoma Corydalis,Radix Salviae Miltiorrhiae, Radix Angelicae sinensis, Ligusticum Chuanxiong, SemenPersicae, Flos Carthami, Radix Aconite, Radix Ginseng, Cortex Cinnamomi, RhizomaZingiberis, Semen Myristicae, Flos Daturae, RadixAucklandiae, Lignum AquilariaeResinatrm and Margarita. A great deal of advantages have been carried out by JTT foropiate detoxification, including less harmful and side effects, high safety and satisfiedeffects in the inhibition of protracted withdrawal symptoms, and effective in therehabilitation of abnormal body functions induced by chronic drug use and good for therehabilitation of abnormal body functions induced by chronic drug use.
Even with so many beneficial effects, the substantial foundation and pharmacologicalmechanism of JTT are still unclear for hundreds of various chemical constituents from thecomprised drugs. And no report of the pharmacokinetic (PK) study of JTT could be foundin literature survey, for not only the complexity of the formula, but also the traceconcentration of the comprised chemical constituents in vivo. Hence, it is imperative toestablish sensitive and comprehensive analytical methods to acquire a better understandingof the material basis and further to elucidate the dynamic changes in vivo.
In the present study, JTT was chosen as the research object. Take advantage of variousinnovation theory and advanced technology, the main chemical components of JTT and themultiple absorbed bioactive components and metabolites in rat plasma after oraladministration of JTT were screened and anlyzed. Besides of that, the bioactivecomponents and metabolites in rat CSF after oral administration of JTT were identified andquantified. Finally, the pharmacokinetic study of the bioactive components in rat plasmaafter oral administration of JTT was successfully clarified. The specific contents are asfollows:
A universally applicable high-performance liquid chromatography/diode-arraydetection (HPLC/DAD) coupled with electrospray tandem mass spectrometry (HPLC/ESI-MS/MS) method was developed for carrying out the comprehensivecharacterization of JTT. Based on the ESI-MSnfragmentation patterns of the referencestandards, a total of101components were identified or tentatively characterized bycomparing their retention times, UV and MS spectra with those of reference standards orthrough the matching of empirical information with those of published components in thein-house library. The characteristic fragmentation pattern of alkaloids, phenolic acids,tanshinones, flavonoid glycosides, cyanogenic glycosides, ginsenosides,2-(2-phenylethyl)chromones, phthalides and gingerol-related compounds were tentatively elucidated usingstructurally-relevant product ions. It was observed that neutral losses of C9H10O3andC9H8O2were the characteristic product ions of scopola alkaloids. Neutral fragmentmandelonitrile was the characteristic ion of cyanogenic glycosides. To our knowledge,tropylium ion and C4H2O unit were the characteristic ions of2-(2-phenylethyl) chromone,which resulted from the Retro-Diels-Alder (RDA) cleavage of the C ring. The resultsindicated that the developed analysis method could be employed as a rapid, effectivetechnique for structural characterization of chemical constituents in TCM. This work isexpected to provide comprehensive information for the quality evaluation andpharmacokinetic studies of JTT.
Based on the serum pharmacochemistry technique and HPLC-DAD/ESI-MS/MS, amethod for screening and analysis of the multiple absorbed bioactive components andmetabolites of JTT in orally dosed rat plasma was developed. Plasma was treated bymethanol precipitation prior to HPLC, and the separation was carried out on a SymmetryC18column, with a linear gradient (0.1%formic acid/water/acetonitrile). Mass spectrawere acquired in negative and positive ion modes, respectively. As a result,26bioactivecomponents originated from JTT and5metabolites were tentatively identified in orallydosed rat plasma by comparing their retention time and MS spectra with those of authenticstandards and literature data. It is concluded that an effective and reliable analyticalmethod was set up for screening the bioactive components of Chinese herbal medicine,which provided a meaningful basis for further pharmacology and active mechanismresearch of JTT.
Take advantage of the combination of liquid chromatography tandem of time-of-flightmass spectrometry (LC-Q-TOF-MS/MS) and liquid chromatography tandam of triplequaduapole mass spectrometry (LC-QqQ-MS) technique, a method for fast quantification and quantitation of the multiple bioactive components and metabolites of JTT in orallydosed rat cerebrospinal fluid (CSF) was developed. CSF was treated by methanolprecipitation prior to liquid chromatography, and the separation was carried out on a HSST3column, with a linear gradient (0.1%formic acid/water/acetonitrile). Mass spectra wereacquired in both full scan mode and targeted MS/MS mode. By comparing the retentiontime and the accurate mass and the MS/MS spectrum of blank CSF, dosed CSF and JTT,11prototype components and3metabolites were tentatively identified. In order to confirm theidentification results, the6target components in rat CSF were further quantitativelydetermined by the LC-QqQ-MS. This experiment provides a rapid method of highsensitivity for the detection of trace component, provides a strategy to study the materialbasis for the efficacy of TCM and will provide some reference for the further study ofmechanism of drug action.
A specific and reliable LC-ESI-MS/MS method was developed for the simultaneousdetermination of tetrahydropalmatine (THP), tetrahydroberineper (THB),tetrahydrocoptisine (THC) and corydaline (CDL) in rat plasma using jatrorrhizine asinternal standard. Plasma samples were pretreated by protein precipitation with acetonitrile.Chromatographic separation was performed on a Zorbax Eclipse Plus C18column (3.0mm×100mm,1.8μm) with gradient elution using acetonitrile–0.1%formic acid water asmobile phase at a flow rate of0.3mL/min. The detection was carried out by atriple–quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. Themass transition ion-pair was followed as m/z35→6.1292.1, m/z324.1→176.0, m/z340.1→176.0, and m/z370.3→192.1for THP, THC, THB and CDL. Linear calibrationcurves were obtained over the range of0.2–2000ng/mL, and the method limits were2.0ng/mL for THC,0.2ng/mL for THB,1.0ng/mL for THP, and0.4ng/mL for CDL,respectively. The mean recovery of the analytes ranged from85.51%to93.99%. The intra-and inter-day precisions were in the range of1.21–4.73%and the accuracies were between92.23%and98.23%. The validated method was successfully applied to a pharmacokineticstudy of THP, THB, THC and CDL in rat plasma following oral administration of Jitaitablets.
A LC-ESI-MS/MS method was developed and validated for the simultaneousdetermination of amygdalin (ADL), danshensu (DSS), ferulic acid (FA), hydroxysaffloryellow A (HSYA), salvianolic acid A (SAA) and salvianolic acid B (SAB) in rat plasma. Plasma samples were pretreated by protein precipitation with acetonitrile. LC separationwas performed on a Zorbax Eclipse Plus C18column (3.0mm×100mm I.D,1.8μm)with gradient elu-tion using a mobile phase consisting of acetonitrile-0.1%formic acid inwater at a flow rate of0.3mL/min. ESI-MS spectra was acquired in negative ion multiplereaction monitoring mode. The mass transition ion-pair was followed as m/z456.→0323.1, m/z197.3→178.8, m/z193.0→133.9, m/z611.1→325.2, m/z493.0→295.0,and m/z717.0→519.0for ADL, DSS, FA, HSYA, SAA and SAB, respectively. Allana-lytes showed good linearity over a wide concentration range (r>0.99). The lower limitof quantification was7ng/mL,2ng/mL,4ng/mL,1ng/mL,2ng/mL, and4ng/mL forADL, DSS, FA, HSYA, SAA and SAB, respectively. The mean recovery of the analytesranged from86.29%to93.16%. The intra-and inter-day precisions were in the range of1.50–9.98%and the accuracies were between91.17%and99.46%. The validated methodwas successfully applied to a pharmacokinetic study of the six hydrophilic components inrat plasma after oral administration of Jitai tablets.
本研究选择疗效确切的戒毒中药“济泰片”为研究对象，综合运用各种创新理论及先进的技术手段，从济泰片中主要化学成分、入血成分及入脑成分的识别等几个方面阐明济泰片药效物质基础；同时，对其药效物质基础的体内动态变化过程进行研究，为济泰片的临床药物监测和用药安全提供科学依据。具体研究内容如下：
首先，采用高效液相色谱串联二极管阵列检测器/电喷雾质谱法（HPLCDAD/ESIMS/MS）对济泰片中主要化学成分进行全面系统的表征。在对标准品母离子碎片离子的裂解规律进行分析基础上，通过对图谱中各化合物的保留时间，紫外（UV）和质谱图谱与标准品及相关文献比较，最终共鉴定了济泰片中包括生物碱类、酚酸类、丹参酮类、黄酮类、氰苷类、人参皂苷类、2[2苯乙基]色原酮类、苯酞内酯类及姜酚类化合物在内的101个化学成分，并对九类化合物的特征性裂解规律进行了总结和分析研究。在正离子模式条件下，莨菪类生物碱的裂解规律主要表现为中性丢失C9H10O3和C9H8O2单元。氰苷类化合物主要表现为中性丢失苯乙醇腈单元。卓鎓离子与C4H2O单元是2[2苯乙基]色原酮裂解中的特征性碎片，其形成过程主要为C环的RDA裂解。本研究首次对济泰片的化学成分进行了系统整体研究，建立的方法可以快速、有效地确定济泰片中主要化学成分，为济泰片的质量评价和药效物质基础研究提供大量化学信息和有力的技术支持。
在对济泰片中化学成分全面定性的基础上，本研究利用“血清药物化学理论”结合HPLCDAD/ESIMS/MS技术对济泰片入血成分进行了定性分析。SD大鼠灌胃给予济泰片1h后，肝门静脉取血，高速离心取上清。血清样品经甲醇沉淀后进行LC-MS分析。采用Waters XTerra C18色谱柱，以乙腈-水（0.1%甲酸）梯度洗脱，在正负离子模式下分别采集其质谱信息。通过综合比较分析济泰片提取液、给药大鼠血浆及空白大鼠血浆的提取离子流色谱图，并与标准品及文献数据比对，首次鉴定了济泰片中26个原型入血成分及5个代谢产物，包括6个人参皂苷类，5个生物碱类，5个苯酞内酯类，3个酚酸类，2个丹参酮类，2个氰苷类，2个姜酚类及1个查耳酮类化合物，代谢产物分别是延胡索乙素葡萄糖醛酸结合物、乙酰基丹参素、6-姜酚葡萄糖醛酸结合物、氢化丹参酮ⅡA葡萄糖醛酸结合物、氢化去氢丹参酮IIA的葡萄糖醛酸结合物。本研究首次建立了一种快速筛选大鼠口服济泰片后入血成分的整体方法，并且本研究检测的部分入血成分与相关戒毒活性的报道一致。该方法的建立不仅有助于阐释济泰片的入血成分，而且为济泰片药代动力学研究提供标志性化合物。
济泰片主要用于阿片成瘾的脱毒治疗，其作用的靶部位主要为中枢神经系统，本章采用脑脊液药物化学的理论与方法，结合快速液相色谱串联四级杆飞行时间质谱（RRLC-Q-TOF-MS/MS）技术对大鼠灌服济泰片后入脑成分进行了全面的定性分析。通过比较空白脑脊液、给药脑脊液及济泰片提取液中化学成分的差异，首次鉴定了包括生物碱类和苯酞内酯类在内的11个原型成分和3个代谢产物。同时采用快速液相色谱串联三重四级杆质谱（RRLC-QqQ-MS/MS）技术对已鉴定的部分化合物进行目标性检测，并定量了给药大鼠脑脊液中的6个成分，各成分的含量分别为：东莨菪碱1.678ng/mL，四氢小檗碱0.024ng/mL，四氢黄连碱0.014ng/mL，原阿片碱0.162ng/mL，延胡索乙素0.587ng/mL及延胡索甲素0.051ng/mL。结果表明，生物碱类和苯酞内酯类成分为济泰片作用于中枢神经系统的主要活性成分，与相关文献报道一致。本研究建立了一种快速、灵敏、准确检测中药复方体内的极微量成分的方法，为中药复方药效物质基础研究提供有力的技术支持，筛选到的目标成分可以作为作用机制研究的标志性成分。
在前述研究基础上，本章对济泰片的主要成分体内药代动力学行为进行了探讨。SD大鼠经灌胃给予济泰片15g/kg大鼠体重，于24h内采集不同时间点大鼠血浆。分别定量血浆中的四个生物碱（四氢黄连碱、四氢小檗碱、延胡索乙素及延胡索甲素）及六个酚酸类（丹参素、阿魏酸、丹酚酸A、丹酚酸B、苦杏仁苷及羟基红花色素A）化合物。血浆样品经乙腈沉淀蛋白预处理，以药根碱和没食子酸作为内标，采用亚微米粒径（1.8μm）分析柱结合RRLC-QqQ-MS/MS的多反应监测模式，分别在正离子模式下对血浆中叔铵型生物碱，与负离子模式下血浆中酚酸类成分进行监测。针对上述不同类型化合物分别采用不同的分析柱与质谱采集模式，通过对样品前处理条件、液相条件及质谱条件的优化，最终分别实现正离子模式下单针8min对血浆中4个生物碱的监测，及负离子模式下单针7min对其余成分的监测。四氢黄连碱、四氢小檗碱、延胡索乙素及延胡索甲素的最低检测限分别为2.0ng/mL、0.2ng/mL、1.0ng/mL及0.4ng/mL，而苦杏仁苷、丹参素、阿魏酸、羟基红花色素A、丹酚酸A及丹酚酸B的最低检测限分别为7.0ng/mL、2.0ng/mL、4.0ng/mL、1.0ng/mL、2.0ng/mL及4.0ng/mL。目标分析物的平均回收率范围从85.51%-93.99%，日内和日间精密度均处于1.21-4.73%的范围内。其最低定量限、精确度、准确度、回收率与基质效应均满足FDA对生物样本分析的要求。研究发现四种生物碱虽然具有相似的结构，但其体内药代动力学参数却表现出明显的不同，但都出现双峰现象。丹参素、阿魏酸、丹酚酸A及丹酚酸B的药代动力学参数中可看出各化合物在吸收和消除行为中均存在明显差异，这可能与化合物不同的理化性质及复方中化学成分相互作用相关。
Jitai tablets (JTT), an important TCM prescription in treating opiate addiction sinceQing dynasty, has been proved to be very safe and effective in the inhibition of protractedwith-drawal symptoms with less harmful side effects, which have been already approvedfor the treatment of opiate addiction by the Chinese State Food and Drug Administration(SFDA). JTT is prepared from fifteen medicinal materials, including Rhizoma Corydalis,Radix Salviae Miltiorrhiae, Radix Angelicae sinensis, Ligusticum Chuanxiong, SemenPersicae, Flos Carthami, Radix Aconite, Radix Ginseng, Cortex Cinnamomi, RhizomaZingiberis, Semen Myristicae, Flos Daturae, RadixAucklandiae, Lignum AquilariaeResinatrm and Margarita. A great deal of advantages have been carried out by JTT foropiate detoxification, including less harmful and side effects, high safety and satisfiedeffects in the inhibition of protracted withdrawal symptoms, and effective in therehabilitation of abnormal body functions induced by chronic drug use and good for therehabilitation of abnormal body functions induced by chronic drug use.
Even with so many beneficial effects, the substantial foundation and pharmacologicalmechanism of JTT are still unclear for hundreds of various chemical constituents from thecomprised drugs. And no report of the pharmacokinetic (PK) study of JTT could be foundin literature survey, for not only the complexity of the formula, but also the traceconcentration of the comprised chemical constituents in vivo. Hence, it is imperative toestablish sensitive and comprehensive analytical methods to acquire a better understandingof the material basis and further to elucidate the dynamic changes in vivo.
In the present study, JTT was chosen as the research object. Take advantage of variousinnovation theory and advanced technology, the main chemical components of JTT and themultiple absorbed bioactive components and metabolites in rat plasma after oraladministration of JTT were screened and anlyzed. Besides of that, the bioactivecomponents and metabolites in rat CSF after oral administration of JTT were identified andquantified. Finally, the pharmacokinetic study of the bioactive components in rat plasmaafter oral administration of JTT was successfully clarified. The specific contents are asfollows:
A universally applicable high-performance liquid chromatography/diode-arraydetection (HPLC/DAD) coupled with electrospray tandem mass spectrometry (HPLC/ESI-MS/MS) method was developed for carrying out the comprehensivecharacterization of JTT. Based on the ESI-MSnfragmentation patterns of the referencestandards, a total of101components were identified or tentatively characterized bycomparing their retention times, UV and MS spectra with those of reference standards orthrough the matching of empirical information with those of published components in thein-house library. The characteristic fragmentation pattern of alkaloids, phenolic acids,tanshinones, flavonoid glycosides, cyanogenic glycosides, ginsenosides,2-(2-phenylethyl)chromones, phthalides and gingerol-related compounds were tentatively elucidated usingstructurally-relevant product ions. It was observed that neutral losses of C9H10O3andC9H8O2were the characteristic product ions of scopola alkaloids. Neutral fragmentmandelonitrile was the characteristic ion of cyanogenic glycosides. To our knowledge,tropylium ion and C4H2O unit were the characteristic ions of2-(2-phenylethyl) chromone,which resulted from the Retro-Diels-Alder (RDA) cleavage of the C ring. The resultsindicated that the developed analysis method could be employed as a rapid, effectivetechnique for structural characterization of chemical constituents in TCM. This work isexpected to provide comprehensive information for the quality evaluation andpharmacokinetic studies of JTT.
Based on the serum pharmacochemistry technique and HPLC-DAD/ESI-MS/MS, amethod for screening and analysis of the multiple absorbed bioactive components andmetabolites of JTT in orally dosed rat plasma was developed. Plasma was treated bymethanol precipitation prior to HPLC, and the separation was carried out on a SymmetryC18column, with a linear gradient (0.1%formic acid/water/acetonitrile). Mass spectrawere acquired in negative and positive ion modes, respectively. As a result,26bioactivecomponents originated from JTT and5metabolites were tentatively identified in orallydosed rat plasma by comparing their retention time and MS spectra with those of authenticstandards and literature data. It is concluded that an effective and reliable analyticalmethod was set up for screening the bioactive components of Chinese herbal medicine,which provided a meaningful basis for further pharmacology and active mechanismresearch of JTT.
Take advantage of the combination of liquid chromatography tandem of time-of-flightmass spectrometry (LC-Q-TOF-MS/MS) and liquid chromatography tandam of triplequaduapole mass spectrometry (LC-QqQ-MS) technique, a method for fast quantification and quantitation of the multiple bioactive components and metabolites of JTT in orallydosed rat cerebrospinal fluid (CSF) was developed. CSF was treated by methanolprecipitation prior to liquid chromatography, and the separation was carried out on a HSST3column, with a linear gradient (0.1%formic acid/water/acetonitrile). Mass spectra wereacquired in both full scan mode and targeted MS/MS mode. By comparing the retentiontime and the accurate mass and the MS/MS spectrum of blank CSF, dosed CSF and JTT,11prototype components and3metabolites were tentatively identified. In order to confirm theidentification results, the6target components in rat CSF were further quantitativelydetermined by the LC-QqQ-MS. This experiment provides a rapid method of highsensitivity for the detection of trace component, provides a strategy to study the materialbasis for the efficacy of TCM and will provide some reference for the further study ofmechanism of drug action.
A specific and reliable LC-ESI-MS/MS method was developed for the simultaneousdetermination of tetrahydropalmatine (THP), tetrahydroberineper (THB),tetrahydrocoptisine (THC) and corydaline (CDL) in rat plasma using jatrorrhizine asinternal standard. Plasma samples were pretreated by protein precipitation with acetonitrile.Chromatographic separation was performed on a Zorbax Eclipse Plus C18column (3.0mm×100mm,1.8μm) with gradient elution using acetonitrile–0.1%formic acid water asmobile phase at a flow rate of0.3mL/min. The detection was carried out by atriple–quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. Themass transition ion-pair was followed as m/z35→6.1292.1, m/z324.1→176.0, m/z340.1→176.0, and m/z370.3→192.1for THP, THC, THB and CDL. Linear calibrationcurves were obtained over the range of0.2–2000ng/mL, and the method limits were2.0ng/mL for THC,0.2ng/mL for THB,1.0ng/mL for THP, and0.4ng/mL for CDL,respectively. The mean recovery of the analytes ranged from85.51%to93.99%. The intra-and inter-day precisions were in the range of1.21–4.73%and the accuracies were between92.23%and98.23%. The validated method was successfully applied to a pharmacokineticstudy of THP, THB, THC and CDL in rat plasma following oral administration of Jitaitablets.
A LC-ESI-MS/MS method was developed and validated for the simultaneousdetermination of amygdalin (ADL), danshensu (DSS), ferulic acid (FA), hydroxysaffloryellow A (HSYA), salvianolic acid A (SAA) and salvianolic acid B (SAB) in rat plasma. Plasma samples were pretreated by protein precipitation with acetonitrile. LC separationwas performed on a Zorbax Eclipse Plus C18column (3.0mm×100mm I.D,1.8μm)with gradient elu-tion using a mobile phase consisting of acetonitrile-0.1%formic acid inwater at a flow rate of0.3mL/min. ESI-MS spectra was acquired in negative ion multiplereaction monitoring mode. The mass transition ion-pair was followed as m/z456.→0323.1, m/z197.3→178.8, m/z193.0→133.9, m/z611.1→325.2, m/z493.0→295.0,and m/z717.0→519.0for ADL, DSS, FA, HSYA, SAA and SAB, respectively. Allana-lytes showed good linearity over a wide concentration range (r>0.99). The lower limitof quantification was7ng/mL,2ng/mL,4ng/mL,1ng/mL,2ng/mL, and4ng/mL forADL, DSS, FA, HSYA, SAA and SAB, respectively. The mean recovery of the analytesranged from86.29%to93.16%. The intra-and inter-day precisions were in the range of1.50–9.98%and the accuracies were between91.17%and99.46%. The validated methodwas successfully applied to a pharmacokinetic study of the six hydrophilic components inrat plasma after oral administration of Jitai tablets.
引文
[1]United Nations Office on Drugs and Crime.2004World Drug Report. United Nations Publication.2004:58-64
[2]秦伯益.近年来我国阿片类戒毒药物的研究进展.中国药物滥用防治杂志,1996,14(3):2-5
[3]Friedman H, Newton C, Klein TW. Microbial Infections, Immunomodulation, and Drugs of Abuse. ClinMicroboil Rev.2003,16(2):209-219
[4]姜佐宁.药物成瘾的临床与治疗.人民卫生出版社,1996,7-19
[5]高源,梁爽,陈海生.戒毒药物研究进展.药学实践杂志,2006,24(6):324-326
[6]Simentov R. Chronic morphine alters dopamine transporter density in the rat brain：possible role in themechanism of drug addiction. Neuroscience Letters,1993,163(2):121-124
[7]Handbook JM, Rence MJ. The interaction of buprenorphine with the opiate and endogenous opioidpeptides. Amsterdam: Eisevier North. Holland,1976,295-297
[8]马赛,马骏雄,仝黎,王跃民,裴建明.阿片成瘾机制研究进展.中华神经外科疾病研究杂志,2007,6(6):563-564
[9]谭北平,李勇辉,隋南.药物依赖过程中多巴胺受体的作用及其研究进展.中国药物依赖性杂志,2003,12(2):81-85
[10]刘菊妍,同萍,周促瑛.中医对阿片类依赖戒断综合症的认识及辩治方法.中国中医基础医学杂志,2000,6(8):3
[11]郑有顺,苏军凯.中药戒毒的现状问题与建议.中国中医药信息杂志,1999,6(5):19-21
[12]郭洁,黄伟.中医药戒毒研究的历史及近况.河南中医,2008,28(2):85-87
[13]高学敏,宋树立,白晓菊.浅析中医药戒毒的科学性.中国药物滥用防治杂志,2001,(l):3
[14]宋普球,陈光辉,刘竹焕.阿片成瘾的治疗及戒毒中药的研究进展.现代中西医结合杂志,2005,14(23):3173-3174
[15]郭松,江佐宁,王有德.中药福康片与盐酸可乐定治疗阿片类戒断症状的临床对照研究.中国药物依赖性通报,1995,(4):210-212
[16]刘锐克,徐国柱,段砺瑕.益安口服液用于海洛因依赖者脱毒Ⅳ期临床评价.中国药物依赖性杂志,2001,10(3):200-203
[17]叶玉山,李建辉,林致浮.中药戒毒灵的制备质控和临床疗效.海峡药学,2005,15(5):6-8
[18]徐凤洲,何勇.参附脱毒胶囊治疗阿片类戒断症状的临床观察.成都中医药大学学报,2001,24(3):14-17
[19]张国恩,李表,候君才.东唐毒克胶囊治疗阿片类戒断症状32例临床观察.中医杂志,1998,39(6):357-358
[20]Shi J, Lu L. Traditional Chinese medicine in treatment of opiate addiction1. Acta pharmacologica sinica2006,27(10):1303-1308
[21]邓金昆,李经才.近年来戒毒药物的研究进展.沈阳药科大学学报,2003,7(10):1558-1559
[22]陆苏南,潘励山,李芳.济泰片吗啡依赖性大鼠和猴的脱毒疗效评价.中国药物滥用防治杂志,1998,(3):37-42
[23]朱家谷,宁可永,刘炳林.新药研究中的非临床药物依赖性研究与评价.中国药科大学学报,2008,39(4):373-375
[24]Pushpa VT. Biological Mechanisms end Perinatal Exposure to Abused Drugs. National Institute onDrug Abuse Research Monograph.2004:158
[25]Tomkins DM, Sellers EM. Addiction and the brain: the role of neurotransmitters in the cause endtreatment of drug dependence. Canadian Medical Association Journa.2001,164(6):817-821
[26]Nestler EJ, Aghajanian GK. Molecular and cellular basis of addiction. Science.1997,278(5335):58-63
[27]Deborah CM. Dopamine transport function is devated in cocaine users. Journal of Neurochemistry.2002,81:292-300
[28]Volkow ND. Association of Dopamine Transporter Reduction with Psychomotor Impairment inMethamphetamine Abusers. Airiericen Journal of Psychiatry,2001,158:3
[29]Lin z, Uhl GR. Dopamine Transporter Mutants with Cocaine Resistanceen d Normal Dopamine UptakeProvide Targets for Cocaine Antagonism. Molecular Pharmacology,2002,61:885-891
[30]曲巧敏,李争,屈冰.瘾消舒合剂戒断阿片成瘾的临床观察.河南中医,1996,16(2):39-40
[31]刘振明,陈萍,衣秀义.洋金花对吗啡镇痛作用耐受性的影响.时珍国医国药,1996,7(4):210-211
[32]高学敏,宋树立,白晓菊.浅析中医药戒毒的科学性.中国药物滥用防治杂志,2001,8(1):3-9
[33]何方,余涓,陈崇宏.丹参有效部位对吗啡依赖性小鼠位置偏爱效应的影响.中草药,2007,38(3):405-408
[34]丘宏强,陈崇宏,余涓.丹参提取物对小鼠吗啡身体依赖性的影响.中草药,2005,36(5):720-723
[35]刘忠华,张树平,李娜.川芎嗪对小鼠吗啡戒断症状的抑制作用.中国现代应用药学,2000,17(2):97-99
[36]胡发明,胡红.丁川芎嗪的实验研究及临床应用.中医研究,2004, I7(3):57-60
[37]高剑峰,王晓辉,邱学才.川芎嗪可抑制吗啡戒断大鼠的高压及血清单胺类递质的升高.河南中医药学刊,2002,17(4):19-20
[38]王睿,梁鑫淼.中药复方的复杂性特征与方法学探讨.现代中药研究与实践,2004,7:42-44
[39]王喜军.中药及中药复方的血清药物化学研究.世界科学技术-中药现代化,2002,4(2):1-4
[40]罗国安,梁琼麟,张荣利.化学物质组学与中药方剂研究－兼析清开灵复方物质基础研究.世界科学技术-中医药现代化,2006,8(1):6-15
[41]严诗楷,赵静,窦圣姗.基于系统生物学与网络生物学的现代中药复方研究体系,中国天然药物,2009,7:249-259
[42]田代真一.“血清蘖理学”“血清蘖化学”.汉方黎理学加岛始圭蔡物血中浓度测定新世界. TDM研究,1988,(5):5
[43]Y.H. Lv, X. Zhang, X. Liang, X.R. Liu, W.X. Dai, W.D. Zhang. Characterization of the constituents inrat biological fluids after oral administration of Fufang Danshen tablets by ultra-performance liquidchromatography/quadrupole time-of-flight mass spectrometry, J. Pharm. Biomed. Anal.2010:155-159
[44]P. Jiang, R.H. Liu, W.D. Zhang. Analysis of the constituents in rat plasma after oral administration ofShexiang Baoxin pill by HPLC-ESI-MS/MS. Biomedical Chromatography,2008,69:659-664
[45]Y.H.Hu, P. Jiang, R.H. Liu, W.D. Zhang. Plasma pharmacochemistry based approach to screeningpotential bioactive components in Huang-Lian-Jie-Du-Tang using high performance liquidchromatography coupled with mass spectrometric detection. Journal of ethnopharmacology, Journal ofEnthopharmacology2011,8:11
[46]梅建勋,张伯礼,陆融.中药脑脊液药理学研究方法的初建-对中药影响的星形胶质细胞神经营养作用的观察.中草药,2000,31:523-526
[47]梅建勋,张伯礼,陆融.中药脑脊液药理学方法的建立:清脑益智方对谷氨酸损伤神经保护作用的实验研究.天津中医,1999,16:25-28
[48]Homma M, Oka K, Yamada T, Niitsuma T, Ihto H, Takahashi N. A strategy for discovering biologicallyactive compounds with high probability in traditional Chinese herb remedies: an application ofSaiboku-To in bronchial asthma. Analytical biochemistry,1992,202(1):179-187
[49]Homma M, Oka K, Taniguchi C, Niitsuma T, Hayashi T. Systematic Analysis of Post administrativeSaibokuo Urine by Liquid Chromatography to Determine Pharmacokinetics of Traditional ChineseMedicine. Biomedical Chromatography,1998,11(3):125-131
[50]程雪龙.中药药物代谢动力学研究现状及问题分析.黑龙江医药,2011,24(5):712-714
[51]Liu Y, Li X, Li Y, Wang L, Xue M. Simultaneous determination of danshensu, rosmarinic acid,cryptotanshinone, tanshinone IIA, tanshinone I and dihydrotanshinone I by liquid chromatographicmass spectrometry and the application to pharmacokinetics in rats. Journal of Pharmaceutical andBiomedical Analysis,53(3):698-704
[52]Zhang YJ, Wu L, Zhang QL, Li J, Yin FX, Yuan Y. Pharmacokinetics of phenolic compounds ofDanshen extract in rat blood and brain by microdialysis sampling. Journal of Ethnopharmacology,136(1):129-136
[53]Jin G, Xue X, Zhang F, Zhang X, Xu Q, Jin Y, Liang X. Prediction of retention times and peak shapeparameters of unknown compounds in traditional Chinese medicine under gradient conditions by ultraperformance liquid chromatography. Analytica Chimica Acta,2008,628(1):95-103
[54]Qi J, Jin X, Huang L, Ping Q. Simultaneous determination of hydroxysafflor yellow A and ferulic acidin rat plasma after oral administration of the co extractum of Rhizoma chuanxiong and Flos Carthami byHPLC diode array detector. Biomedical Chromatography,2007,21(8):816-822
[55]Liu AH, Guo H, Min Y, Lin YH, Sun J-H, Man X, Guo DA. Detection, characterization andidentification of phenolic acids in Danshen using high-performance liquid chromatography with diodearray detection and electrospray ionization mass spectrometry. Journal of Chromatography B,2007,1161(1-2):170-182
[56]Wu YT, Chen YF, Hsieh YJ, Jaw I, Shiao MS, Tsai TH. Bioavailability of salvianolic acid B inconscious and freely moving rats. International Journal of Pharmaceutics,2006,326(1):25-31
[57]Yunfei, L, Haibin, Q,Yiyu, C.Identification of major constituents in the traditional Chinese medicine"QI-SHEN-YI-QI" dropping pill by high-performance liquid chromatography coupled with diode arraydetection-electrospray ionization tandem mass spectrometry. Journal of pharmaceutical and biomedicalanalysis,2008,47(2):407-412
[58]Ye, M, Guo, D. Analysis of bufadienolides in the Chinese drug ChanSu by high performance liquidchromatography with atmospheric pressure chemical ionization tandem mass spectrometry. Rapidcommunications in mass spectrometry,2005,19(13):1881-1892
[59]Liu, M, Li, Y, Zhang, F, Yang, L, Chou, G, Wang, Z, Hu, Z. Chromatographic fingerprinting analysis ofDanshen root (Salvia miltiorrhiza Radix et Rhizoma) and its preparations using high performance liquidchromatography with diode array detection and electrospray mass spectrometry (HPLC DAD ESI/MS).Journal of separation science,2007,30(14):2256-2267
[60]Li SL, Song JZ, Qiao CF. Zhou Y, Qian K. Lee KH, Xu HX. A novel strategy to rapidly explorepotential chemical markers for the discrimination between raw and processed Radix Rehmanniae byUHPLC TOFMS with multivariate statistical analysis. Journal of pharmaceutical and biomedicalanalysis,51(4):812-823
[61]Li SL, Shen H, Zhu LY, Xu J, Jia XB, Zhang HM, Lin G, Cai H, Cai BC, Chen SL.Ultra-high-performance liquid chromatography quadrupole/time of flight mass spectrometry basedchemical profiling approach to rapidly reveal chemical transformation of sulfur-fumigated medicinalherbs, a case study on white ginseng. Journal of Chromatography A.2010,33(4):456-457
[62]Cai F, Xu W, Wei H, Sun L, Gao S, Yang Q, Feng J, Zhang F, Chen W. Simultaneous determination ofactive xanthone glycosides, timosaponins and alkaloids in rat plasma after oral administration ofZi-Shen Pill extract for the pharmacokinetic study by liquid chromatography tandem mass spectrometry.Journal of Chromatography B,878(21):1845-1851
[63]Xu W, Luo H, Zhang Y, Shan L, Li H, Yang M, Liu R, Zhang W. Simultaneous determination of fivemain active bufadienolides of Chan Su in rat plasma by liquid chromatography tandem massspectrometry. Journal of Chromatography B,2007,859(2):157-163
[1]Li LJ, Xing XF, Shao HX. Preparation of traditional Chinese herbs on addiction detoxification: recentprogress. Chin. Med.2003,11(34):20–22
[2]Shi J, Liu YL, Fang YX, Xu GZ, Zhai HF, Lu L. Traditional Chinese medicine in treatment of opiateaddiction. Acta Pharmacol. Sin.2006,23(27):1303–1308
[3]Xiong JG, Xiao ZX, Li J, Qin DS, Min MS, Yang JH, Wang YH, Yan L, Shu QL. Clinical effect of Jitaitablet combined with lofexidine in the treatment of heroin dependence. Chin. J. Drug Depend.2001,22(4):290–292
[4]Tu QX, Zhao HG, Cheng YP, Chen YM, Huang XP, Chen Y.M, Han M. Comparision study on clinicalefficacy of Jitai capsule with lofexidine in the treatment of opiate addicts. Chin. J. Drug Depend.1999,11(4):285–287
[5]Zhang HY, Hu P, Luo GA, Liang QL, Wang YL, Yan SK, Wang YM. Screening and identification ofmulti-component in Qingkailing injection using combination of liquid chromatography/time-of-flightmass spectrometry and liquid chromatography/diode array detection/ion trap mass spectrometry. Anal.Chim. Acta2006,577(8):190–200
[6]Xu SJ, Yang L, Zeng X, Zhang M, Wang ZT. Characterization of compounds in the Chinese herbal drugMu-Dan-Pi by liquid chromatography coupled to electrospray ionization mass spectrometry. RapidCommun. Mass Spectrom.2006,12(20):3275–3288
[7]Chen Y, Fan G.R, Zhang QY, Wu HL, Wu YT. Fingerprint analysis of the fruits of Cnidium monnieriextract by high-performance liquid chromatography-diode array detection-electrospray ionizationtandem mass spectrometry. J. Pharm. Biomed. Anal.2007,18(43):926–936
[8]Chen LL, Qi J, Chang YX, Zhu DN, Yu BY. Identification and determination of the major constituentsin traditional Chinese medicinal formula Danggui-Shaoyao-San by LC-DAD-ESI-MS/MS. J. Pharm.Biomed. Anal.2009,12(50):127–137
[9]Quirantes-Piné R, Funes L, Micol V, Segura-Carretero A, Fernández-Gutiérrez A. High-performanceliquid chromatography with diode array detection coupled to electrospray time-of-flight and ion-traptandem mass spectrometry to identify phenolic compounds from a lemon verbena extract. J. Chromatogr.A2009,8(1216):5391–5397
[10]Lou ZY, Zhang H, Gong CG, Zhu ZY, Zhao L, Xu YJ, Wang B, Zhang GQ. Analysis of lignans inSchisandra chinensis and rat plasma by high performance liquid chromatography diode array detection,time of flight mass spectrometry and quadrupole ion trap mass spectrometry. Rapid Commun. MassSpectrom.2009,8(23):831–842
[11]García-Reyes JF, Hernando MD, Ferrer C, Molina-Díaz A, Fernández-Alba AR. Large scale pesticidemultiresidue methods in food combining liquid chromatography-time-of-flight mass spectrometry andtandem mass spectrometry. Anal. Chem.2007,3(79):7308–7323
[12]Ferrer I, Heine CE, Thurman EM. Combination of LC/TOF-MS and LC/ion trap MS/MS for theidentification of diphenhydramine in sediment samples. Anal. Chem.2004,3(76):1437–1444
[13]Dugo P, Cacciola\F, Donato P, Jacques RA, Caram o EB, Mondello L. High efficiency liquidchromatography techniques coupled to mass spectrometry for the characterization of mate extracts. J.Chromatogr. A2009,14(1216):7213–7221
[14]Chuang WC, Young DS, Liu LK, Sheu SJ. Liquid chromatographic-electrospray mass spectrometricanalysis of Coptidis Rhizoma. J. Chromatogr. A1996,755(4):19–26
[15]Cheng Z, Guo Y, Wang H, Chen G. Qualitative and quantitative analysis of quaternary ammoniumalkaloids from Rhizoma Corydalis by matrix-assisted laser desorption/ionization Fourier transform massspectrometry coupled with a selective precipitation reaction using Reinecke salt. Anal. Chim. Acta2006,555(9):269–277
[16]Zhang HG, Sun Y, Duan MY, Chen YJ, Zhong DF, Zhang HQ. Separation and identification ofAconitum alkaloids and their metabolites in human urine. Toxicon2005,46(2):500–506
[17]Yue H, Pi Z, Song F, Liu Z. Studies on the aconitine-type alkaloids in the roots of AconitumCarmichaeli Debx. by LC/ESIMS/MSn. Talanta2009,77(8):1800–1807
[18]Chen H, Chen Y, Wang H, Du P. Analysis of scopolamine and its eighteen metabolites in rat urine byliquid chromatography-tandem mass spectrometry. Talanta2005,67(4):984–991
[19]Liu AH, Guo H, Ye M, Lin YH, Sun JH, Guo DA. Detection, characterization and identification ofphenolic acids in Danshen using high-performance liquid chromatography with diode array detectionand electrospray ionization mass spectrometry. J. Chromatogr. A2007,1161(5):170–182
[20]Shen Y, Wang X, Xu L, Liu X, Chao R. Characterization of metabolites in rat plasma after intravenousadministration of salvianolic acid A by liquid chromatography/time of flight mass spectrometry andliquid chromatography/diode array detection/ion trap mass spectrometry. Rapid Commun. MassSpectrom.2009,23(9):1810–1816
[21]Liu AH, Lin YH, Yang M, Guo H, Guan HS, Sun JH, Guo D.A. Development of the fingerprints for thequality of the roots of Salvia miltiorrhiza and its related preparations by LC-DAD and LC-MSn. J.Chromatogr. B2007,846(3):32–41
[22]Li P, Wang GJ, Li J, Hao HP, Zheng CN. Characterization of metabolites of tanshinone IIA in rats byliquid chromatography/tandem mass spectrometry. J. Mass Spectrom.2006,41(4):670–684
[23]Jin Y, Xiao Y, Zhang F, Xue X, Xu Q, Liang XM. Systematic screening and characterization offlavonoid glycosides in Carthamus tinctorius L. by liquid chromatography/UV diode-arraydetection/electrospray ionization tandem mass spectrometry. J. Pharm. Biomed. Anal.2008,46(3):418–430
[24]Wen AD, Yang J, Jia YY, Yang ZF, Tian Y, Wu Y, Wang ZR, He ZG. A rapid and sensitive liquidchromatography-tandem mass spectrometry (LC-MS/MS) method for the determination ofhydroxysafflor yellow A in human plasma: Application to a pharmacokinetic study. J. Chromatogr. B2008,876(4):41–46
[25]Ge B, Chen H, Han F, Chen Y. Identification of amygdalin and its major metabolites in rat urine byLC-MS/MS. J. Chromatogr. B2007,857(9):281–286
[26]Liu S, Cui M, Liu Z, Song F, Mo W. Structural analysis of saponins from medicinal herbs usingelectrospray ionization tandem mass spectrometry. J. Am. Soc. Mass Spectrom.2004,15(2):133–141
[27]Woo SS, Song JS, Lee JY, In DS, Chung HJ, Liu, JR, Choi DW. Selection of high ginsenosideproducing ginseng hairy root lines using targeted metabolic analysis. Phytochemistry,2004,65(2):2751–2761
[28]Liu Y, Yang J, Cai Z. Chemical investigation on Sijunzi decoction and its two major herbs Panaxginseng and Glycyrrhiza uralensis by LC/MS/MS. J. Pharm. Biomed. Anal.2006,41(3):1642–1647
[29]Yagura T, Ito M, Kiuchi F, Honda G, Shimada Y. Four new2-(2-phenylethyl) chromone derivatives fromwithered wood of Aquilaria sinensis. Chem. Pharm. Bull.2003,51(8):560–564
[30]Alkhathlan H, Al-Hazimi H, Al-Dhalaan F, Mousa A. Three2-(2-phenylethyl) chromones and twoterpenes from agarwood. Nat. Prod. Res.2005,19(7):367–372
[31]Yi T, Leung KSY, Lu GH, Chan K, Zhang H. Simultaneous qualitative and quantitative analyses of themajor constituents in the rhizome of Ligusticum Chuanxiong using LC-DAD-MS. Chem. Pharm. Bull.2006,54(2):255–259
[32]Zschocke S, Klaiber I, Bauer R, Vogler B. LC-coupled spectroscopic techniques (UV, MS, NMR) forthe structure elucidation of phthalides in Ligusticum chuanxiong. Mol. Divers.2005,9(1):33–39
[33]Yang F, Xiao YS, Zhang FF, Xue, XY, Xu, Q, Liang, XM. High performance liquidchromatography-mass spectrometry analysis of radix Angelica sciensis. Acta Pharmacol. Sin.2006,41(7):1078–1081
[34]Jiang HL, Somogyi A, Timmermann BN, Gang DR. Instrument dependence of electrospray ionizationand tandem mass spectrometric fragmentation of the gingerols. Rapid Commun. Mass Spectrom.2006,20(8):3089–3096
[35]Huang HY, Kuo KL, Hsieh YZ. Determination of cinnamaldehyde, cinnamic acid, paeoniflorin,glycyrrhizin and [6]-gingerol in the traditional Chinese medicinal preparation Kuei-chih-tang bycyclodextrin-modified micellar electrokinetic chromatography. J. Chromatogr. A1997,771(5):267–274
[36]Jiang HL, Xie Z, Koo HJ, McLaughlin SP, Timmermann BN, David RG. Metabolic profiling andphylogenetic analysis of medicinal Zingiber species: Tools for authentication of ginger (Zingiberofficinale Rosc.). Phytochemistry,2006,67(4):1673–1685
[1]Hosseinzadeh H, Nourbakhsh M. Effect of Rosmarinus of ninalis L. aerial parts extract on morphinewithdrawal syndrome in mice. Phytotherapy Research,2003,17(8):938-941
[2]Choi S, Jung SY, Rhim H, Jeong SW, Lee SM, Nah SY. Evidence that ginsenosides prevent thedevelopment of opioid tolerance at the central nervous system. Life Sciences,2000,67(8):969-975
[3]Chang CK, Lin MT. DL-Tetrahydropalmatine may act through inhibition of amygdaloid release ofdopamine to inhibit an epileptic attack in rats. Neuroscience Letters,2001,307(3):163-166
[4]Jiang P, Liu R, Dou S, Liu L, Zhang W, Chen Z, Xu R, Ding J. Analysis of the constituents in rat plasmaafter oral administration of Shexiang Baoxin pill by HPLC ESI MS/MS. Biomedical Chromatography,2009,23(12):1333-1343
[5]Homma M, Oka K, Yamada T, Niitsuma T, Ihto H, Takahashi N. A strategy for discovering biologicallyactive compounds with high probability in traditional Chinese herb remedies: an application ofSaiboku-To in bronchial asthma. Analytical Biochemistry,1992,202(1):179-187
[6]Homma M, Oka K, Taniguchi C, Niitsuma T, Hayashi T. Systematic Analysis of Post administrativeSaibokuo Urine by Liquid Chromatography to Determine Pharmacokinetics of Traditional ChineseMedicine. Biomedical Chromatography,1998,11(3):125-131
[7]Pan JY, Cheng YY. Identification and analysis of absorbed and metabolic components in rat plasma afteroral administration of shuangdan granule by HPLC-DAD/ESI-MS/MS. Journal of Pharmaceutical andBiomedical Analysis,2006,42(5):565-572
[8]Wang P, Liang Y-Z, Chen B-M, Zhou N, Yi LZ, Yu Y, Yi Z-B. Quantitative determination of amantadinein human plasma by liquid chromatography mass spectrometry and the application in a bioequivalencestudy. Journal of Pharmaceutical and Biomedical Analysis,2007,43(4):1519-1525
[9]Lou Z, Zhang H, Gong C, Zhu Z, Zhao L, Xu Y, Wang B, Zhang G. Analysis of lignans in Schisandrachinensis and rat plasma by high performance liquid chromatography diode array detection, time offlight mass spectrometry and quadrupole ion trap mass spectrometry. Rapid Communications in MassSpectrometry,2009,23(6):831-842
[10]Liu S, Cui M, Liu Z, Song F, Mo W. Structural analysis of saponins from medicinal herbs usingelectrospray ionization tandem mass spectrometry. Journal of the American Society for MassSpectrometry,2004,15(2):133-141
[11]Lai C, Li S, Yu H, Wan J, Kan K, Wang Y. A rapid HPLC ESI-MS/MS for qualitative and quantitativeanalysis of saponins in UESETONG injection. Journal of Pharmaceutical and Biomedical Analysis,2006,40(3):669-678
[12]Liu AH, Guo H, Min Y, Lin Y-H, Sun J-H, Man X, Guo D-A. Detection, characterization andidentification of phenolic acids in Danshen using high-performance liquid chromatography with diodearray detection and electrospray ionization mass spectrometry. Journal of Chromatography B,2007,1161(1-2):170-182
[13]Shen Y, Wang X, Xu L, Liu X, Chao R. Characterization of metabolites in rat plasma after intravenousadministration of salvianolic acid A by liquid chromatography/time of flight mass spectrometry andliquid chromatography/ion trap mass spectrometry. Rapid Communications in Mass Spectrometry,2009,23(12):1810-1816
[14]Liu AH, Lin YH, Yang M, Guo H, Guan SH, Sun JH, Guo DA. Development of the fingerprints for thequality of the roots of Salvia miltiorrhiza and its related preparations by HPLC-DAD and LC-MS(n).Journal of Chromatography B,2007,846(1-2):32
[15]Ge B, Chen H, Han F, Chen Y. Identification of amygdalin and its major metabolites in rat urine by LCMS/MS. Journal of Chromatography B,2007,857(2):281-286
[16]Jin Y, Zhang X, Shi H, Xiao Y, Ke Y, Xue X, Zhang F, Liang X. Characterization of Chlycosylquinochalcones in Carthamus tinctorius L. by ultraperformance liquid chromatography coupled withquadrupole time of flight mass spectrometry. Rapid Communications in Mass Spectrometry,2008,22(8):1275-1287
[17]Sun JH, Yang M, Wang XM, Xu M, Liu AH, Guo DA. Identification of tanshinones and theirmetabolites in rat bile after oral administration of TTE-50, a standardized extract of Salvia miltiorrhizaby HPLC ESI DAD MSn. Journal of Pharmaceutical and Biomedical Analysis,2007,44(2):564-574
[18]Teng JW, Li Dl, Luo AD. Identification and Characterization of Supercritical Fluid Extracts of RhizomaChuanxiong by High Performance Liquid Chromatography/Ion Trap Mass Spectrometry. Journal ofInstrumental Analysis,2007,26(3):356-361
[19]Ding B, Zhou T, Fan G, Hong Z, Wu Y. Qualitative and quantitative determination of ten alkaloids intraditional Chinese medicine Corydalis yanhusuo WT Wang by LC-MS/MS and LC-DAD. Journal ofPharmaceutical and Biomedical Analysis,,2007,45(2):219-226
[20]Jiang H, S mlyom AM, Timmermann BN, Gang DR. Characterization of gingerol related compounds inginger rhizome (Zingiber officinale Rosc.) by high performance liquid chromatography/electrosprayionization mass spectrometry. Rapid Communications in Mass Spectrometry,2005,19(20):2957-2964
[21]Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J.A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. New EnglandJournal of Medicine,2006,354(10):1001-1010
[22]Nakazawa T, Ohsawa K. Metabolism of [6]-gingerol in rats. Life sciences,2002,70(18):2165-2175
[23]Pfeiffer E, Heuschmid FF, Kranz S, Metzler M. Microsomal hydroxylation and glucuronidation of[6]-gingerol. Journal of Agricultural and Food Chemistry,2006,54(23):8769-8774
[24]Li P, Wang G, Li J, Hao H, Zheng C. Characterization of metabolites of tanshinone IIA in rats by liquidchromatography/tandem mass spectrometry. Journal of Mass Spectrometry,2006,41(5):670-684
[1]秦伯益.近年来我国阿片类戒毒药物的研究进展.中国药物滥用防治杂志,1996,5(3):2-5
[2]宋普球,陈光辉,刘竹焕,钱韵旭.阿片成瘾的治疗及戒毒中药的研究进展.现代中西医结合杂志,2006,14(23):3173-3174
[3]高源,梁爽,陈海生.戒毒药物研究进展.药学实践杂志,2006,24(6):324-326.药学实践杂志,2007,24(6):324-328
[4]马赛,马骏雄,仝黎,王跃民,裴建明.阿片成瘾机制研究进展.中华神经外科疾病研究杂志,2007,6(6):563-564
[5]Pushpa VT. Biological Mechanisms end Perinatal Exposure to Abused Drugs. National Institute onDrug Abuse Research Monograph.2004:158
[6]谭北平,李勇辉,隋南.药物依赖过程中多巴胺受体的作用及其研究进展.中国药物依赖性杂志,2003,12(2):81-85
[7]陈惠红,朱永平. NMDA受体拮抗剂的奖赏效应与阿片类药物精神依赖性.中国药物依赖性杂志,2002,11(1):2-5
[8]王玢,罗非,韩济生.阿片成瘾机制研究进展及治疗展望生理科学进展.1998,29(4):295-300
[9]晏庭林,李琳,刘新社.阿片受体及阿片肤研究进展.中国药物依赖性杂志,2009,5(3):257-259
[10]陈惠红，朱永平. NMDA受体拮抗剂的奖赏效应与阿片类药物精神依赖性.中国药物依赖性杂志,2002,13(1):59-61
[11]Wikoff WR, Pendyala G, Siuzdak G, Fox HS. Metabolomic analysis of the cerebrospinal fluid revealschanges in phospholipase expression in the CNS of SIV-infected macaques. Journal of clinicalinvestigation,2008,118(7):2661-2664
[12]Chen H, Chen Y, Wang H, Du P, Han F, Zhang H. Analysis of scopolamine and its eighteen metabolitesin rat urine by liquid chromatography-tandem mass spectrometry. Talanta,2005,67(5):984-991
[13]Takemoto H, Ito M, Shiraki T, Yagura T, Honda G. Sedative effects of vapor inhalation of agarwood oiland spikenard extract and identification of their active components. Journal of natural medicines,2008,62(1):41-46
[14]Ding B, Zhou T, Fan G, Hong Z, Wu Y. Qualitative and quantitative determination of ten alkaloids intraditional Chinese medicine Corydalis yanhusuo WT Wang by LC MS/MS and LC DAD.Journal of pharmaceutical and biomedical analysis,2007,45(2):219-226
[15]Zhang J, Jin Y, Dong J, Xiao Y, Feng J, Xue X, Zhang X, Liang X. Systematic screening andcharacterization of tertiary and quaternary alkaloids from corydalis yanhusuo WT Wang usingultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Talanta,2009,78(2):513-522
[16]Fan ZC, Xie CJ, Zhang ZQ. Simultaneous Quantitation of Tetrahydropalmatine and Protopine in RabbitPlasma by HPLC DAD, and Application to Pharmacokinetic Studies. Chromatographia,2006,64(9):577-581
[17]Cheng ZH, Guo YL, Wang HY, Chen GQ. Qualitative and quantitative analysis of quaternaryammonium alkaloids from Rhizoma Corydalis by matrix-assisted laser desorption/ionization Fouriertransform mass spectrometry coupled with a selective precipitation reaction using Reinecke salt.Analytica chimica acta,2006,555(2):269-277
[18]Guo J, Duan JA, Shang EX, Tang Y, Qian D. Determination of ligustilide in rat brain after nasaladministration of essential oil from Rhizoma Chuanxiong. Fitoterapia,2009,80(3):168-172
[19]侯鹏飞,宿树兰,段金廒,刘汉清.液质联用技术分析延胡索中的生物碱类成分.中国医药导报,2008,5(11):48-49
[20]牟昀雅,余伯阳. HPLC/MS/MS法分离鉴定罗通定在大鼠胆汁中的代谢产物.中国天然药物,2007,4(6):448-451
[21]Kong L, Yu Z, Bao Y, Su X, Zou H, Li X. Screening and analysis of an antineoplastic compound inRhizoma Chuanxiong by means of in vitro metabolism and HPLC-MS. Analytical and bioanalyticalchemistry,2006,386(2):264-274
[1]Shi J, LU L. Traditional Chinese medicine in treatment of opiate addiction1. Acta pharmacologica sinica,2006,27(10):1303-1308
[2]Li L, Xing X, Shao H. Preparation of traditional Chinese herbs on addiction detoxification: recentprogress. Chin Med,2003,34(2):2012
[3]Xiong JG, Xiao ZX, Li J, Qin DS, Min MS, Yang JH, Wang YH, Yan L, Shu QL. Clinical effect of Jitaitablet combined with lofexidine in the treatment of heroin dependence. Chin. J. Drug Depend.2001,22(4):290–292
[4]Tu QX, Zhao HG, Cheng YP, Chen YM, Huang XP, Chen Y.M, Han M. Comparision study on clinicalefficacy of Jitai capsule with lofexidine in the treatment of opiate addicts. Chin. J. Drug Depend.1999,11(4):285–287
[5]Wang S, Liu L, Wang L, Jiang P, Zhang J, Zhang W, Liu R. Screening and analysis of the multipleabsorbed bioactive components and metabolites in rat plasma after oral administration of Jitai tablets byhigh performance liquid chromatography/diode array detection coupled with electrospray ionizationtandem mass spectrometry. Rapid Communications in Mass Spectrometry,24(11):1641-1652
[6]Wang L, Zhou GB, Liu P, Song JH, Liang Y, Yan XJ, Xu F, Wang BS, Mao JH, Shen ZX. Dissection ofmechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment forpromyelocytic leukemia. Proceedings of the National Academy of Sciences,2008,105(12):4826-4831
[7]Ling H, Wu L, Li L. Corydalis yanhusuo rhizoma extract reduces infarct size and improves heartfunction during myocardial ischemia/reperfusion by inhibiting apoptosis in rats. Phytotherapy research,2006,20(6):448-453
[8]Mantsch JR, Li SJ, Risinger R, Awad S, Katz E, Baker DA, Yang Z. Levo-tetrahydropalmatineattenuates cocaine self-administration and cocaine-induced reinstatement in rats. Psychopharmacology,2007,192(4):581-591
[9]Ding B, Zhou T, Fan G, Hong Z, Wu Y. Qualitative and quantitative determination of ten alkaloids intraditional Chinese medicine Corydalis yanhusuo WT Wang by LC-MS/MS and LC-DAD. Journal ofpharmaceutical and biomedical analysis,2007,45(2):219-226
[10]Ma ZZ, Xu W, Jensen NH, Roth BL, Liu Chen LY, Lee DY. Isoquinoline alkaloids isolated fromCorydalis yanhusuo and their binding affinities at the dopamine D1receptor. Molecules,2008,13(9):2303-2312
[11]Zhang J, Jin Y, Dong J, Xiao Y, Feng J, Xue X, Zhang X, Liang X. Systematic screening andcharacterization of tertiary and quaternary alkaloids from corydalis yanhusuo WT Wang usingultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Talanta,2009,78(2):513-522
[12]Shimizu T, Iwata S-i, Morioka H, Masuyama T, Fukuda T, Nomoto M. Antinociceptive mechanism ofL-DOPA. Pain,2004,110(1):246-249
[13]Wang JB, Mantsch JR. l-tetrahydropalamatine: a potential new medication for the treatment of cocaineaddiction. Future,4(2):177-186
[14]Xi ZX, Gilbert J, Campos AC, Kline N, Ashby CR, Hagan JJ, Heidbreder CA, Gardner EL. Blockade ofmesolimbic dopamine D3receptors inhibits stress-induced reinstatement of cocaine-seeking in rats.Psychopharmacology,2004,176(1):57-65
[15]Liu Y, Liang J, Yan L, Su R, Wu C, Gong Z. Effects of l-etrahydropalmatine on locomotor sensitizationto oxycodone in mice. Acta pharmacologica sinica,2005,26(5):533-538
[16]Chu H, Jin G, Friedman E, Zhen X. Recent development in studies of tetrahydroprotoberberines:mechanism in antinociception and drug addiction. Cellular and molecular neurobiology,2008,28(4):491-499
[17]Wang C, Wang S, Fan G, Zou H. Screening of antinociceptive components in Corydalis yanhusuo WTWang by comprehensive two-dimensional liquid chromatography/tandem mass spectrometry. Analyticaland bioanalytical chemistry,396(5):1731-1740
[18]Fan ZC, Xie CJ, Zhang ZQ. Simultaneous Quantitation of Tetrahydropalmatine and Protopine in RabbitPlasma by HPLC-DAD, and Application to Pharmacokinetic Studies. Chromatographia,2006,64(9):577-581
[19]Hong Z, Fan G, Le J, Chai Y, Yin X, Wu Y. Brain pharmacokinetics and tissue distribution oftetrahydropalmatine enantiomers in rats after oral administration of the racemate. Biopharmaceutics&drug disposition,2006,27(3):111-117
[20]Hong Z, Fan G, Chai Y, Yin X, Wen J, Wu Y. Chiral liquid chromatography resolution andstereoselective pharmacokinetic study of tetrahydropalmatine enantiomers in dogs. Journal ofchromatography B,2005,826(1):108-113
[21]He D, Chen B, Tian Q, Yao S. Simultaneous determination of five anthraquinones in medicinal plantsand pharmaceutical preparations by HPLC with fluorescence detection. Journal of pharmaceutical andbiomedical analysis,2009,49(4):1123-1127
[22]Matuszewski B, Constanzer M, Chavez-Eng C. Strategies for the assessment of matrix effect inquantitative bioanalytical methods based on HPLC-MS/MS. Analytical Chemistry,2003,75(13):3019-3030
[23]Yu S, Pang X, Deng Y, Liu L, Liang Y, Liu X, Xie L, Wang G, Wang X. A sensitive and specific liquidchromatography mass spectrometry method for simultaneous determination of berberine, palmatine,coptisine, epiberberine and jatrorrhizine from Coptidis Rhizoma in rat plasma. International Journal ofMass Spectrometry,2007,268(1):30-37
[24]Deng Y, Liao Q, Li S, Bi K, Pan B, Xie Z. Simultaneous determination of berberine, palmatine andjatrorrhizine by liquid chromatography tandem mass spectrometry in rat plasma and its application in apharmacokinetic study after oral administration of coptis vodia herb couple. Journal of chromatographyB,2008,863(2):195-205
[25]Zhou H. Pharmacokinetic strategies in deciphering atypical drug absorption profiles. The Journal ofClinical Pharmacology,2003,43(3):211-227
[26]Zhang XP, Li ZJ, Liu D-R. Progress in research into the mechanism of Radix salviae miltiorrhizae intreatment of acute pancreatitis. Hepatobiliary Pancreat Dis Int,2006,5(4):501-504
[27]Homma M, Oka K, Taniguchi C, Niitsuma T, Hayashi T. Systematic Analysis of Post administrativeSaiboku to Urine by Liquid Chromatography to Determine Pharmacokinetics of Traditional ChineseMedicine. Biomedical Chromatography,1998,11(3):125-131
[28]Fang XS, Hao J, Zhou H, Zhu L, Wang J, Song F. Pharmacological studies on the sedative-hypnoticeffect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen)extracts and the synergistic effect of their combinations. Phytomedicine,17(1):75-80
[29]Kinoshita K, Kawai T, Imaizumi T, Akita Y, Koyama K, Takahashi K. Anti-emetic principles of Inulalinariaefolia flowers and Forsythia suspensa fruits. Phytomedicine,1996,3(1):51-58
[30]Barone E, Calabrese V, Mancuso C. Ferulic acid and its therapeutic potential as a hormetin forage-related diseases. Biogerontology,2009,10(2):97-108
[31]Chueh WH, Lin JY. Berberine, an isoquinoline alkaloid in herbal plants, protects pancreatic islets andserum lipids in nonobese diabetic mice. Journal of agricultural and food chemistry,59(14):8021-8027
[32]Sun X, Wei X, Qu S, Zhao Y, Zhang X. Hydroxysafflor Yellow A suppresses thrombin generation andinflammatory responses following focal cerebral ischemia heperfusion in rats. Bioorganic&medicinalchemistry letters,20(14):4120-4124
[33]Zhan JY, Zheng KY, Zhu KY, Bi CW, Zhang WL, Du CY, Fu Q, Dong TT, Choi RC, Tsim KW.Chemical and biological assessment of Angelicae Sinensis Radix after processing with wine: anorthogonal array design to reveal the optimized conditions. Journal of agricultural and food chemistry,59(11):6091-6098
[34]Chang HK, Shin MS, Yang HY, Lee JW, Kim YS, Lee MH, Kim J, Kim KH, Kim CJ. Amygdalininduces apoptosis through regulation of Bax and Bcl-2expressions in human DU145and LNCaPprostate cancer cells. Biological and Pharmaceutical Bulletin,2006,29(8):1597-1602
[35]Rauws A, Olling M, Timmerman A. The pharmacokinetics of amygdalin. Archives of toxicology,1982,49(3):311-319
[36]Li X, Yu C, Cai Y, Liu G, Jia J, Wang Y. Simultaneous determination of six phenolic constituents ofdanshen in human serum using liquid chromatography/tandem mass spectrometry. Journal ofchromatography B,2005,820(1):41-47
[37]Zhou Q, Ding Y, Xiao J. Simultaneous determination of cyanazine, chlorotoluron and chlorbenzuron inenvironmental water samples with SPE multiwalled carbon nanotubes and LC. Chromatographia,2007,65(1):25-30
[38]Zhan Y, Xu J-P, Liang JB, Sheng LS, Xiang BR, Zou QG, Zhang ZJ. Simultaneous LC-MS/MS Analysisof Danshensu, Salvianolic Acid B, and Hydroxysafflor Yellow A in Beagle Dog Plasma, and Applicationof the Method to a Pharmacokinetic Study of Danhong Lyophilized Powder for Injection.Chromatographia,2008,68(1):71-79
[39]Guo X, Chen X, Li L, Shen Z, Wang X, Zheng P, Duan F, Ma Y, Bi K. LC-MS determination andpharmacokinetic study of six phenolic components in rat plasma after taking traditional Chinesemedicinal-preparation: Guanxinning lyophilized powder for injection. Journal of chromatography B2008,873(1):51-58
[40]Wen A, Yang J, Jia Y, Yang Z, Tian Y, Wu Y, Wang Z, He Z. A rapid and sensitive liquidchromatography tandem mass spectrometry (LC MS/MS) method for the determination ofhydroxysafflor yellow A in human plasma: Application to a pharmacokinetic study. Journal ofchromatography B,2008,876(1):41-46
[41]Chang J, Zhang Y. Catalytic Degradation of Amygdalin by Extracellular Enzymes from Aspergillusniger Process Biochemistry.
[42]Ge B, Chen H, Han F, Chen Y. Identification of amygdalin and its major metabolites in rat urine by LCMS/MS. Journal of Chromatography B,2007,857(2):281-286
[43]Jin Y, Zhang X, Shi H, Xiao Y, Ke Y, Xue X, Zhang F, Liang X. Characterization of Chlycosylquinochalcones in Carthamus tinctorius L. by ultraperformance liquid chromatography coupled withquadrupole time of flight mass spectrometry. Rapid Communications in Mass Spectrometry,2008,22(8):1275-1287
[44]Zhang T, Yang X, Zhang P, Zhu M, He Z, Bi K. Determination of Ferulic Acid in Rat Plasma by LiquidChromatography tandem Mass Spectrometry Method: Application to a Pharmacokinetic Study.Analytical Letters,2009,42(14):2157-2169
[45]Wen XD, Qi LW, Li P, Bao KD, Yan XW, Yi L, Li CY. Simultaneous determination ofcalycosin-7-O-beta-D-glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid in rat plasmaafter oral administration of Danggui Buxue Tang extract for their pharmacokinetic studies by liquidchromatography-mass spectrometry. J Chromatogr B,2008,865(1-2):99-105
[46]Zhan Y, Liang J, Sheng L, Xiang B, Zou Q, Zhang W, Xu J. Development and Validation of LiquidChromatography tandem Mass Spectrometry for Simultaneous Determination of the Four ActiveComponents of Danhong Freeze ried Powder Injection in Human Plasma. Analytical Letters,2008,41(5):737-756
[47]Liu Y, Li X, Li Y, Wang L, Xue M. Simultaneous determination of danshensu, rosmarinic acid,cryptotanshinone, tanshinone IIA, tanshinone I and dihydrotanshinone I by liquid chromatographicmass spectrometry and the application to pharmacokinetics in rats. Journal of pharmaceutical andbiomedical analysis,53(3):698-704
[48]Zhang YJ, Wu L, Zhang QL, Li J, Yin FX, Yuan Y. Pharmacokinetics of phenolic compounds ofDanshen extract in rat blood and brain by microdialysis sampling. Journal of ethnopharmacology,136(1):129-136
[49]Jin G, Xue X, Zhang F, Zhang X, Xu Q, Jin Y, Liang X. Prediction of retention times and peak shapeparameters of unknown compounds in traditional Chinese medicine under gradient conditions by ultraperformance liquid chromatography. Analytica Chimica Acta,2008,628(1):95-103
[50]Qi J, Jin X, Huang L, Ping Q. Simultaneous determination of hydroxysafflor yellow A and ferulic acidin rat plasma after oral administration of the co extractum of Rhizoma chuanxiong and Flos Carthami byHPLC diode array detector. Biomedical Chromatography,2007,21(8):816-822
[51]Liu AH, Guo H, Min Y, Lin YH, Sun J-H, Man X, Guo DA. Detection, characterization andidentification of phenolic acids in Danshen using high-performance liquid chromatography with diodearray detection and electrospray ionization mass spectrometry. Journal of chromatography B,2007,1161(1-2):170-182
[52]Wu YT, Chen YF, Hsieh YJ, Jaw I, Shiao MS, Tsai TH. Bioavailability of salvianolic acid B inconscious and freely moving rats. International journal of pharmaceutics,2006,326(1):25-31
[2]秦伯益.近年来我国阿片类戒毒药物的研究进展.中国药物滥用防治杂志,1996,14(3):2-5
[3]Friedman H, Newton C, Klein TW. Microbial Infections, Immunomodulation, and Drugs of Abuse. ClinMicroboil Rev.2003,16(2):209-219
[4]姜佐宁.药物成瘾的临床与治疗.人民卫生出版社,1996,7-19
[5]高源,梁爽,陈海生.戒毒药物研究进展.药学实践杂志,2006,24(6):324-326
[6]Simentov R. Chronic morphine alters dopamine transporter density in the rat brain：possible role in themechanism of drug addiction. Neuroscience Letters,1993,163(2):121-124
[7]Handbook JM, Rence MJ. The interaction of buprenorphine with the opiate and endogenous opioidpeptides. Amsterdam: Eisevier North. Holland,1976,295-297
[8]马赛,马骏雄,仝黎,王跃民,裴建明.阿片成瘾机制研究进展.中华神经外科疾病研究杂志,2007,6(6):563-564
[9]谭北平,李勇辉,隋南.药物依赖过程中多巴胺受体的作用及其研究进展.中国药物依赖性杂志,2003,12(2):81-85
[10]刘菊妍,同萍,周促瑛.中医对阿片类依赖戒断综合症的认识及辩治方法.中国中医基础医学杂志,2000,6(8):3
[11]郑有顺,苏军凯.中药戒毒的现状问题与建议.中国中医药信息杂志,1999,6(5):19-21
[12]郭洁,黄伟.中医药戒毒研究的历史及近况.河南中医,2008,28(2):85-87
[13]高学敏,宋树立,白晓菊.浅析中医药戒毒的科学性.中国药物滥用防治杂志,2001,(l):3
[14]宋普球,陈光辉,刘竹焕.阿片成瘾的治疗及戒毒中药的研究进展.现代中西医结合杂志,2005,14(23):3173-3174
[15]郭松,江佐宁,王有德.中药福康片与盐酸可乐定治疗阿片类戒断症状的临床对照研究.中国药物依赖性通报,1995,(4):210-212
[16]刘锐克,徐国柱,段砺瑕.益安口服液用于海洛因依赖者脱毒Ⅳ期临床评价.中国药物依赖性杂志,2001,10(3):200-203
[17]叶玉山,李建辉,林致浮.中药戒毒灵的制备质控和临床疗效.海峡药学,2005,15(5):6-8
[18]徐凤洲,何勇.参附脱毒胶囊治疗阿片类戒断症状的临床观察.成都中医药大学学报,2001,24(3):14-17
[19]张国恩,李表,候君才.东唐毒克胶囊治疗阿片类戒断症状32例临床观察.中医杂志,1998,39(6):357-358
[20]Shi J, Lu L. Traditional Chinese medicine in treatment of opiate addiction1. Acta pharmacologica sinica2006,27(10):1303-1308
[21]邓金昆,李经才.近年来戒毒药物的研究进展.沈阳药科大学学报,2003,7(10):1558-1559
[22]陆苏南,潘励山,李芳.济泰片吗啡依赖性大鼠和猴的脱毒疗效评价.中国药物滥用防治杂志,1998,(3):37-42
[23]朱家谷,宁可永,刘炳林.新药研究中的非临床药物依赖性研究与评价.中国药科大学学报,2008,39(4):373-375
[24]Pushpa VT. Biological Mechanisms end Perinatal Exposure to Abused Drugs. National Institute onDrug Abuse Research Monograph.2004:158
[25]Tomkins DM, Sellers EM. Addiction and the brain: the role of neurotransmitters in the cause endtreatment of drug dependence. Canadian Medical Association Journa.2001,164(6):817-821
[26]Nestler EJ, Aghajanian GK. Molecular and cellular basis of addiction. Science.1997,278(5335):58-63
[27]Deborah CM. Dopamine transport function is devated in cocaine users. Journal of Neurochemistry.2002,81:292-300
[28]Volkow ND. Association of Dopamine Transporter Reduction with Psychomotor Impairment inMethamphetamine Abusers. Airiericen Journal of Psychiatry,2001,158:3
[29]Lin z, Uhl GR. Dopamine Transporter Mutants with Cocaine Resistanceen d Normal Dopamine UptakeProvide Targets for Cocaine Antagonism. Molecular Pharmacology,2002,61:885-891
[30]曲巧敏,李争,屈冰.瘾消舒合剂戒断阿片成瘾的临床观察.河南中医,1996,16(2):39-40
[31]刘振明,陈萍,衣秀义.洋金花对吗啡镇痛作用耐受性的影响.时珍国医国药,1996,7(4):210-211
[32]高学敏,宋树立,白晓菊.浅析中医药戒毒的科学性.中国药物滥用防治杂志,2001,8(1):3-9
[33]何方,余涓,陈崇宏.丹参有效部位对吗啡依赖性小鼠位置偏爱效应的影响.中草药,2007,38(3):405-408
[34]丘宏强,陈崇宏,余涓.丹参提取物对小鼠吗啡身体依赖性的影响.中草药,2005,36(5):720-723
[35]刘忠华,张树平,李娜.川芎嗪对小鼠吗啡戒断症状的抑制作用.中国现代应用药学,2000,17(2):97-99
[36]胡发明,胡红.丁川芎嗪的实验研究及临床应用.中医研究,2004, I7(3):57-60
[37]高剑峰,王晓辉,邱学才.川芎嗪可抑制吗啡戒断大鼠的高压及血清单胺类递质的升高.河南中医药学刊,2002,17(4):19-20
[38]王睿,梁鑫淼.中药复方的复杂性特征与方法学探讨.现代中药研究与实践,2004,7:42-44
[39]王喜军.中药及中药复方的血清药物化学研究.世界科学技术-中药现代化,2002,4(2):1-4
[40]罗国安,梁琼麟,张荣利.化学物质组学与中药方剂研究－兼析清开灵复方物质基础研究.世界科学技术-中医药现代化,2006,8(1):6-15
[41]严诗楷,赵静,窦圣姗.基于系统生物学与网络生物学的现代中药复方研究体系,中国天然药物,2009,7:249-259
[42]田代真一.“血清蘖理学”“血清蘖化学”.汉方黎理学加岛始圭蔡物血中浓度测定新世界. TDM研究,1988,(5):5
[43]Y.H. Lv, X. Zhang, X. Liang, X.R. Liu, W.X. Dai, W.D. Zhang. Characterization of the constituents inrat biological fluids after oral administration of Fufang Danshen tablets by ultra-performance liquidchromatography/quadrupole time-of-flight mass spectrometry, J. Pharm. Biomed. Anal.2010:155-159
[44]P. Jiang, R.H. Liu, W.D. Zhang. Analysis of the constituents in rat plasma after oral administration ofShexiang Baoxin pill by HPLC-ESI-MS/MS. Biomedical Chromatography,2008,69:659-664
[45]Y.H.Hu, P. Jiang, R.H. Liu, W.D. Zhang. Plasma pharmacochemistry based approach to screeningpotential bioactive components in Huang-Lian-Jie-Du-Tang using high performance liquidchromatography coupled with mass spectrometric detection. Journal of ethnopharmacology, Journal ofEnthopharmacology2011,8:11
[46]梅建勋,张伯礼,陆融.中药脑脊液药理学研究方法的初建-对中药影响的星形胶质细胞神经营养作用的观察.中草药,2000,31:523-526
[47]梅建勋,张伯礼,陆融.中药脑脊液药理学方法的建立:清脑益智方对谷氨酸损伤神经保护作用的实验研究.天津中医,1999,16:25-28
[48]Homma M, Oka K, Yamada T, Niitsuma T, Ihto H, Takahashi N. A strategy for discovering biologicallyactive compounds with high probability in traditional Chinese herb remedies: an application ofSaiboku-To in bronchial asthma. Analytical biochemistry,1992,202(1):179-187
[49]Homma M, Oka K, Taniguchi C, Niitsuma T, Hayashi T. Systematic Analysis of Post administrativeSaibokuo Urine by Liquid Chromatography to Determine Pharmacokinetics of Traditional ChineseMedicine. Biomedical Chromatography,1998,11(3):125-131
[50]程雪龙.中药药物代谢动力学研究现状及问题分析.黑龙江医药,2011,24(5):712-714
[51]Liu Y, Li X, Li Y, Wang L, Xue M. Simultaneous determination of danshensu, rosmarinic acid,cryptotanshinone, tanshinone IIA, tanshinone I and dihydrotanshinone I by liquid chromatographicmass spectrometry and the application to pharmacokinetics in rats. Journal of Pharmaceutical andBiomedical Analysis,53(3):698-704
[52]Zhang YJ, Wu L, Zhang QL, Li J, Yin FX, Yuan Y. Pharmacokinetics of phenolic compounds ofDanshen extract in rat blood and brain by microdialysis sampling. Journal of Ethnopharmacology,136(1):129-136
[53]Jin G, Xue X, Zhang F, Zhang X, Xu Q, Jin Y, Liang X. Prediction of retention times and peak shapeparameters of unknown compounds in traditional Chinese medicine under gradient conditions by ultraperformance liquid chromatography. Analytica Chimica Acta,2008,628(1):95-103
[54]Qi J, Jin X, Huang L, Ping Q. Simultaneous determination of hydroxysafflor yellow A and ferulic acidin rat plasma after oral administration of the co extractum of Rhizoma chuanxiong and Flos Carthami byHPLC diode array detector. Biomedical Chromatography,2007,21(8):816-822
[55]Liu AH, Guo H, Min Y, Lin YH, Sun J-H, Man X, Guo DA. Detection, characterization andidentification of phenolic acids in Danshen using high-performance liquid chromatography with diodearray detection and electrospray ionization mass spectrometry. Journal of Chromatography B,2007,1161(1-2):170-182
[56]Wu YT, Chen YF, Hsieh YJ, Jaw I, Shiao MS, Tsai TH. Bioavailability of salvianolic acid B inconscious and freely moving rats. International Journal of Pharmaceutics,2006,326(1):25-31
[57]Yunfei, L, Haibin, Q,Yiyu, C.Identification of major constituents in the traditional Chinese medicine"QI-SHEN-YI-QI" dropping pill by high-performance liquid chromatography coupled with diode arraydetection-electrospray ionization tandem mass spectrometry. Journal of pharmaceutical and biomedicalanalysis,2008,47(2):407-412
[58]Ye, M, Guo, D. Analysis of bufadienolides in the Chinese drug ChanSu by high performance liquidchromatography with atmospheric pressure chemical ionization tandem mass spectrometry. Rapidcommunications in mass spectrometry,2005,19(13):1881-1892
[59]Liu, M, Li, Y, Zhang, F, Yang, L, Chou, G, Wang, Z, Hu, Z. Chromatographic fingerprinting analysis ofDanshen root (Salvia miltiorrhiza Radix et Rhizoma) and its preparations using high performance liquidchromatography with diode array detection and electrospray mass spectrometry (HPLC DAD ESI/MS).Journal of separation science,2007,30(14):2256-2267
[60]Li SL, Song JZ, Qiao CF. Zhou Y, Qian K. Lee KH, Xu HX. A novel strategy to rapidly explorepotential chemical markers for the discrimination between raw and processed Radix Rehmanniae byUHPLC TOFMS with multivariate statistical analysis. Journal of pharmaceutical and biomedicalanalysis,51(4):812-823
[61]Li SL, Shen H, Zhu LY, Xu J, Jia XB, Zhang HM, Lin G, Cai H, Cai BC, Chen SL.Ultra-high-performance liquid chromatography quadrupole/time of flight mass spectrometry basedchemical profiling approach to rapidly reveal chemical transformation of sulfur-fumigated medicinalherbs, a case study on white ginseng. Journal of Chromatography A.2010,33(4):456-457
[62]Cai F, Xu W, Wei H, Sun L, Gao S, Yang Q, Feng J, Zhang F, Chen W. Simultaneous determination ofactive xanthone glycosides, timosaponins and alkaloids in rat plasma after oral administration ofZi-Shen Pill extract for the pharmacokinetic study by liquid chromatography tandem mass spectrometry.Journal of Chromatography B,878(21):1845-1851
[63]Xu W, Luo H, Zhang Y, Shan L, Li H, Yang M, Liu R, Zhang W. Simultaneous determination of fivemain active bufadienolides of Chan Su in rat plasma by liquid chromatography tandem massspectrometry. Journal of Chromatography B,2007,859(2):157-163
[1]Li LJ, Xing XF, Shao HX. Preparation of traditional Chinese herbs on addiction detoxification: recentprogress. Chin. Med.2003,11(34):20–22
[2]Shi J, Liu YL, Fang YX, Xu GZ, Zhai HF, Lu L. Traditional Chinese medicine in treatment of opiateaddiction. Acta Pharmacol. Sin.2006,23(27):1303–1308
[3]Xiong JG, Xiao ZX, Li J, Qin DS, Min MS, Yang JH, Wang YH, Yan L, Shu QL. Clinical effect of Jitaitablet combined with lofexidine in the treatment of heroin dependence. Chin. J. Drug Depend.2001,22(4):290–292
[4]Tu QX, Zhao HG, Cheng YP, Chen YM, Huang XP, Chen Y.M, Han M. Comparision study on clinicalefficacy of Jitai capsule with lofexidine in the treatment of opiate addicts. Chin. J. Drug Depend.1999,11(4):285–287
[5]Zhang HY, Hu P, Luo GA, Liang QL, Wang YL, Yan SK, Wang YM. Screening and identification ofmulti-component in Qingkailing injection using combination of liquid chromatography/time-of-flightmass spectrometry and liquid chromatography/diode array detection/ion trap mass spectrometry. Anal.Chim. Acta2006,577(8):190–200
[6]Xu SJ, Yang L, Zeng X, Zhang M, Wang ZT. Characterization of compounds in the Chinese herbal drugMu-Dan-Pi by liquid chromatography coupled to electrospray ionization mass spectrometry. RapidCommun. Mass Spectrom.2006,12(20):3275–3288
[7]Chen Y, Fan G.R, Zhang QY, Wu HL, Wu YT. Fingerprint analysis of the fruits of Cnidium monnieriextract by high-performance liquid chromatography-diode array detection-electrospray ionizationtandem mass spectrometry. J. Pharm. Biomed. Anal.2007,18(43):926–936
[8]Chen LL, Qi J, Chang YX, Zhu DN, Yu BY. Identification and determination of the major constituentsin traditional Chinese medicinal formula Danggui-Shaoyao-San by LC-DAD-ESI-MS/MS. J. Pharm.Biomed. Anal.2009,12(50):127–137
[9]Quirantes-Piné R, Funes L, Micol V, Segura-Carretero A, Fernández-Gutiérrez A. High-performanceliquid chromatography with diode array detection coupled to electrospray time-of-flight and ion-traptandem mass spectrometry to identify phenolic compounds from a lemon verbena extract. J. Chromatogr.A2009,8(1216):5391–5397
[10]Lou ZY, Zhang H, Gong CG, Zhu ZY, Zhao L, Xu YJ, Wang B, Zhang GQ. Analysis of lignans inSchisandra chinensis and rat plasma by high performance liquid chromatography diode array detection,time of flight mass spectrometry and quadrupole ion trap mass spectrometry. Rapid Commun. MassSpectrom.2009,8(23):831–842
[11]García-Reyes JF, Hernando MD, Ferrer C, Molina-Díaz A, Fernández-Alba AR. Large scale pesticidemultiresidue methods in food combining liquid chromatography-time-of-flight mass spectrometry andtandem mass spectrometry. Anal. Chem.2007,3(79):7308–7323
[12]Ferrer I, Heine CE, Thurman EM. Combination of LC/TOF-MS and LC/ion trap MS/MS for theidentification of diphenhydramine in sediment samples. Anal. Chem.2004,3(76):1437–1444
[13]Dugo P, Cacciola\F, Donato P, Jacques RA, Caram o EB, Mondello L. High efficiency liquidchromatography techniques coupled to mass spectrometry for the characterization of mate extracts. J.Chromatogr. A2009,14(1216):7213–7221
[14]Chuang WC, Young DS, Liu LK, Sheu SJ. Liquid chromatographic-electrospray mass spectrometricanalysis of Coptidis Rhizoma. J. Chromatogr. A1996,755(4):19–26
[15]Cheng Z, Guo Y, Wang H, Chen G. Qualitative and quantitative analysis of quaternary ammoniumalkaloids from Rhizoma Corydalis by matrix-assisted laser desorption/ionization Fourier transform massspectrometry coupled with a selective precipitation reaction using Reinecke salt. Anal. Chim. Acta2006,555(9):269–277
[16]Zhang HG, Sun Y, Duan MY, Chen YJ, Zhong DF, Zhang HQ. Separation and identification ofAconitum alkaloids and their metabolites in human urine. Toxicon2005,46(2):500–506
[17]Yue H, Pi Z, Song F, Liu Z. Studies on the aconitine-type alkaloids in the roots of AconitumCarmichaeli Debx. by LC/ESIMS/MSn. Talanta2009,77(8):1800–1807
[18]Chen H, Chen Y, Wang H, Du P. Analysis of scopolamine and its eighteen metabolites in rat urine byliquid chromatography-tandem mass spectrometry. Talanta2005,67(4):984–991
[19]Liu AH, Guo H, Ye M, Lin YH, Sun JH, Guo DA. Detection, characterization and identification ofphenolic acids in Danshen using high-performance liquid chromatography with diode array detectionand electrospray ionization mass spectrometry. J. Chromatogr. A2007,1161(5):170–182
[20]Shen Y, Wang X, Xu L, Liu X, Chao R. Characterization of metabolites in rat plasma after intravenousadministration of salvianolic acid A by liquid chromatography/time of flight mass spectrometry andliquid chromatography/diode array detection/ion trap mass spectrometry. Rapid Commun. MassSpectrom.2009,23(9):1810–1816
[21]Liu AH, Lin YH, Yang M, Guo H, Guan HS, Sun JH, Guo D.A. Development of the fingerprints for thequality of the roots of Salvia miltiorrhiza and its related preparations by LC-DAD and LC-MSn. J.Chromatogr. B2007,846(3):32–41
[22]Li P, Wang GJ, Li J, Hao HP, Zheng CN. Characterization of metabolites of tanshinone IIA in rats byliquid chromatography/tandem mass spectrometry. J. Mass Spectrom.2006,41(4):670–684
[23]Jin Y, Xiao Y, Zhang F, Xue X, Xu Q, Liang XM. Systematic screening and characterization offlavonoid glycosides in Carthamus tinctorius L. by liquid chromatography/UV diode-arraydetection/electrospray ionization tandem mass spectrometry. J. Pharm. Biomed. Anal.2008,46(3):418–430
[24]Wen AD, Yang J, Jia YY, Yang ZF, Tian Y, Wu Y, Wang ZR, He ZG. A rapid and sensitive liquidchromatography-tandem mass spectrometry (LC-MS/MS) method for the determination ofhydroxysafflor yellow A in human plasma: Application to a pharmacokinetic study. J. Chromatogr. B2008,876(4):41–46
[25]Ge B, Chen H, Han F, Chen Y. Identification of amygdalin and its major metabolites in rat urine byLC-MS/MS. J. Chromatogr. B2007,857(9):281–286
[26]Liu S, Cui M, Liu Z, Song F, Mo W. Structural analysis of saponins from medicinal herbs usingelectrospray ionization tandem mass spectrometry. J. Am. Soc. Mass Spectrom.2004,15(2):133–141
[27]Woo SS, Song JS, Lee JY, In DS, Chung HJ, Liu, JR, Choi DW. Selection of high ginsenosideproducing ginseng hairy root lines using targeted metabolic analysis. Phytochemistry,2004,65(2):2751–2761
[28]Liu Y, Yang J, Cai Z. Chemical investigation on Sijunzi decoction and its two major herbs Panaxginseng and Glycyrrhiza uralensis by LC/MS/MS. J. Pharm. Biomed. Anal.2006,41(3):1642–1647
[29]Yagura T, Ito M, Kiuchi F, Honda G, Shimada Y. Four new2-(2-phenylethyl) chromone derivatives fromwithered wood of Aquilaria sinensis. Chem. Pharm. Bull.2003,51(8):560–564
[30]Alkhathlan H, Al-Hazimi H, Al-Dhalaan F, Mousa A. Three2-(2-phenylethyl) chromones and twoterpenes from agarwood. Nat. Prod. Res.2005,19(7):367–372
[31]Yi T, Leung KSY, Lu GH, Chan K, Zhang H. Simultaneous qualitative and quantitative analyses of themajor constituents in the rhizome of Ligusticum Chuanxiong using LC-DAD-MS. Chem. Pharm. Bull.2006,54(2):255–259
[32]Zschocke S, Klaiber I, Bauer R, Vogler B. LC-coupled spectroscopic techniques (UV, MS, NMR) forthe structure elucidation of phthalides in Ligusticum chuanxiong. Mol. Divers.2005,9(1):33–39
[33]Yang F, Xiao YS, Zhang FF, Xue, XY, Xu, Q, Liang, XM. High performance liquidchromatography-mass spectrometry analysis of radix Angelica sciensis. Acta Pharmacol. Sin.2006,41(7):1078–1081
[34]Jiang HL, Somogyi A, Timmermann BN, Gang DR. Instrument dependence of electrospray ionizationand tandem mass spectrometric fragmentation of the gingerols. Rapid Commun. Mass Spectrom.2006,20(8):3089–3096
[35]Huang HY, Kuo KL, Hsieh YZ. Determination of cinnamaldehyde, cinnamic acid, paeoniflorin,glycyrrhizin and [6]-gingerol in the traditional Chinese medicinal preparation Kuei-chih-tang bycyclodextrin-modified micellar electrokinetic chromatography. J. Chromatogr. A1997,771(5):267–274
[36]Jiang HL, Xie Z, Koo HJ, McLaughlin SP, Timmermann BN, David RG. Metabolic profiling andphylogenetic analysis of medicinal Zingiber species: Tools for authentication of ginger (Zingiberofficinale Rosc.). Phytochemistry,2006,67(4):1673–1685
[1]Hosseinzadeh H, Nourbakhsh M. Effect of Rosmarinus of ninalis L. aerial parts extract on morphinewithdrawal syndrome in mice. Phytotherapy Research,2003,17(8):938-941
[2]Choi S, Jung SY, Rhim H, Jeong SW, Lee SM, Nah SY. Evidence that ginsenosides prevent thedevelopment of opioid tolerance at the central nervous system. Life Sciences,2000,67(8):969-975
[3]Chang CK, Lin MT. DL-Tetrahydropalmatine may act through inhibition of amygdaloid release ofdopamine to inhibit an epileptic attack in rats. Neuroscience Letters,2001,307(3):163-166
[4]Jiang P, Liu R, Dou S, Liu L, Zhang W, Chen Z, Xu R, Ding J. Analysis of the constituents in rat plasmaafter oral administration of Shexiang Baoxin pill by HPLC ESI MS/MS. Biomedical Chromatography,2009,23(12):1333-1343
[5]Homma M, Oka K, Yamada T, Niitsuma T, Ihto H, Takahashi N. A strategy for discovering biologicallyactive compounds with high probability in traditional Chinese herb remedies: an application ofSaiboku-To in bronchial asthma. Analytical Biochemistry,1992,202(1):179-187
[6]Homma M, Oka K, Taniguchi C, Niitsuma T, Hayashi T. Systematic Analysis of Post administrativeSaibokuo Urine by Liquid Chromatography to Determine Pharmacokinetics of Traditional ChineseMedicine. Biomedical Chromatography,1998,11(3):125-131
[7]Pan JY, Cheng YY. Identification and analysis of absorbed and metabolic components in rat plasma afteroral administration of shuangdan granule by HPLC-DAD/ESI-MS/MS. Journal of Pharmaceutical andBiomedical Analysis,2006,42(5):565-572
[8]Wang P, Liang Y-Z, Chen B-M, Zhou N, Yi LZ, Yu Y, Yi Z-B. Quantitative determination of amantadinein human plasma by liquid chromatography mass spectrometry and the application in a bioequivalencestudy. Journal of Pharmaceutical and Biomedical Analysis,2007,43(4):1519-1525
[9]Lou Z, Zhang H, Gong C, Zhu Z, Zhao L, Xu Y, Wang B, Zhang G. Analysis of lignans in Schisandrachinensis and rat plasma by high performance liquid chromatography diode array detection, time offlight mass spectrometry and quadrupole ion trap mass spectrometry. Rapid Communications in MassSpectrometry,2009,23(6):831-842
[10]Liu S, Cui M, Liu Z, Song F, Mo W. Structural analysis of saponins from medicinal herbs usingelectrospray ionization tandem mass spectrometry. Journal of the American Society for MassSpectrometry,2004,15(2):133-141
[11]Lai C, Li S, Yu H, Wan J, Kan K, Wang Y. A rapid HPLC ESI-MS/MS for qualitative and quantitativeanalysis of saponins in UESETONG injection. Journal of Pharmaceutical and Biomedical Analysis,2006,40(3):669-678
[12]Liu AH, Guo H, Min Y, Lin Y-H, Sun J-H, Man X, Guo D-A. Detection, characterization andidentification of phenolic acids in Danshen using high-performance liquid chromatography with diodearray detection and electrospray ionization mass spectrometry. Journal of Chromatography B,2007,1161(1-2):170-182
[13]Shen Y, Wang X, Xu L, Liu X, Chao R. Characterization of metabolites in rat plasma after intravenousadministration of salvianolic acid A by liquid chromatography/time of flight mass spectrometry andliquid chromatography/ion trap mass spectrometry. Rapid Communications in Mass Spectrometry,2009,23(12):1810-1816
[14]Liu AH, Lin YH, Yang M, Guo H, Guan SH, Sun JH, Guo DA. Development of the fingerprints for thequality of the roots of Salvia miltiorrhiza and its related preparations by HPLC-DAD and LC-MS(n).Journal of Chromatography B,2007,846(1-2):32
[15]Ge B, Chen H, Han F, Chen Y. Identification of amygdalin and its major metabolites in rat urine by LCMS/MS. Journal of Chromatography B,2007,857(2):281-286
[16]Jin Y, Zhang X, Shi H, Xiao Y, Ke Y, Xue X, Zhang F, Liang X. Characterization of Chlycosylquinochalcones in Carthamus tinctorius L. by ultraperformance liquid chromatography coupled withquadrupole time of flight mass spectrometry. Rapid Communications in Mass Spectrometry,2008,22(8):1275-1287
[17]Sun JH, Yang M, Wang XM, Xu M, Liu AH, Guo DA. Identification of tanshinones and theirmetabolites in rat bile after oral administration of TTE-50, a standardized extract of Salvia miltiorrhizaby HPLC ESI DAD MSn. Journal of Pharmaceutical and Biomedical Analysis,2007,44(2):564-574
[18]Teng JW, Li Dl, Luo AD. Identification and Characterization of Supercritical Fluid Extracts of RhizomaChuanxiong by High Performance Liquid Chromatography/Ion Trap Mass Spectrometry. Journal ofInstrumental Analysis,2007,26(3):356-361
[19]Ding B, Zhou T, Fan G, Hong Z, Wu Y. Qualitative and quantitative determination of ten alkaloids intraditional Chinese medicine Corydalis yanhusuo WT Wang by LC-MS/MS and LC-DAD. Journal ofPharmaceutical and Biomedical Analysis,,2007,45(2):219-226
[20]Jiang H, S mlyom AM, Timmermann BN, Gang DR. Characterization of gingerol related compounds inginger rhizome (Zingiber officinale Rosc.) by high performance liquid chromatography/electrosprayionization mass spectrometry. Rapid Communications in Mass Spectrometry,2005,19(20):2957-2964
[21]Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J.A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. New EnglandJournal of Medicine,2006,354(10):1001-1010
[22]Nakazawa T, Ohsawa K. Metabolism of [6]-gingerol in rats. Life sciences,2002,70(18):2165-2175
[23]Pfeiffer E, Heuschmid FF, Kranz S, Metzler M. Microsomal hydroxylation and glucuronidation of[6]-gingerol. Journal of Agricultural and Food Chemistry,2006,54(23):8769-8774
[24]Li P, Wang G, Li J, Hao H, Zheng C. Characterization of metabolites of tanshinone IIA in rats by liquidchromatography/tandem mass spectrometry. Journal of Mass Spectrometry,2006,41(5):670-684
[1]秦伯益.近年来我国阿片类戒毒药物的研究进展.中国药物滥用防治杂志,1996,5(3):2-5
[2]宋普球,陈光辉,刘竹焕,钱韵旭.阿片成瘾的治疗及戒毒中药的研究进展.现代中西医结合杂志,2006,14(23):3173-3174
[3]高源,梁爽,陈海生.戒毒药物研究进展.药学实践杂志,2006,24(6):324-326.药学实践杂志,2007,24(6):324-328
[4]马赛,马骏雄,仝黎,王跃民,裴建明.阿片成瘾机制研究进展.中华神经外科疾病研究杂志,2007,6(6):563-564
[5]Pushpa VT. Biological Mechanisms end Perinatal Exposure to Abused Drugs. National Institute onDrug Abuse Research Monograph.2004:158
[6]谭北平,李勇辉,隋南.药物依赖过程中多巴胺受体的作用及其研究进展.中国药物依赖性杂志,2003,12(2):81-85
[7]陈惠红,朱永平. NMDA受体拮抗剂的奖赏效应与阿片类药物精神依赖性.中国药物依赖性杂志,2002,11(1):2-5
[8]王玢,罗非,韩济生.阿片成瘾机制研究进展及治疗展望生理科学进展.1998,29(4):295-300
[9]晏庭林,李琳,刘新社.阿片受体及阿片肤研究进展.中国药物依赖性杂志,2009,5(3):257-259
[10]陈惠红，朱永平. NMDA受体拮抗剂的奖赏效应与阿片类药物精神依赖性.中国药物依赖性杂志,2002,13(1):59-61
[11]Wikoff WR, Pendyala G, Siuzdak G, Fox HS. Metabolomic analysis of the cerebrospinal fluid revealschanges in phospholipase expression in the CNS of SIV-infected macaques. Journal of clinicalinvestigation,2008,118(7):2661-2664
[12]Chen H, Chen Y, Wang H, Du P, Han F, Zhang H. Analysis of scopolamine and its eighteen metabolitesin rat urine by liquid chromatography-tandem mass spectrometry. Talanta,2005,67(5):984-991
[13]Takemoto H, Ito M, Shiraki T, Yagura T, Honda G. Sedative effects of vapor inhalation of agarwood oiland spikenard extract and identification of their active components. Journal of natural medicines,2008,62(1):41-46
[14]Ding B, Zhou T, Fan G, Hong Z, Wu Y. Qualitative and quantitative determination of ten alkaloids intraditional Chinese medicine Corydalis yanhusuo WT Wang by LC MS/MS and LC DAD.Journal of pharmaceutical and biomedical analysis,2007,45(2):219-226
[15]Zhang J, Jin Y, Dong J, Xiao Y, Feng J, Xue X, Zhang X, Liang X. Systematic screening andcharacterization of tertiary and quaternary alkaloids from corydalis yanhusuo WT Wang usingultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Talanta,2009,78(2):513-522
[16]Fan ZC, Xie CJ, Zhang ZQ. Simultaneous Quantitation of Tetrahydropalmatine and Protopine in RabbitPlasma by HPLC DAD, and Application to Pharmacokinetic Studies. Chromatographia,2006,64(9):577-581
[17]Cheng ZH, Guo YL, Wang HY, Chen GQ. Qualitative and quantitative analysis of quaternaryammonium alkaloids from Rhizoma Corydalis by matrix-assisted laser desorption/ionization Fouriertransform mass spectrometry coupled with a selective precipitation reaction using Reinecke salt.Analytica chimica acta,2006,555(2):269-277
[18]Guo J, Duan JA, Shang EX, Tang Y, Qian D. Determination of ligustilide in rat brain after nasaladministration of essential oil from Rhizoma Chuanxiong. Fitoterapia,2009,80(3):168-172
[19]侯鹏飞,宿树兰,段金廒,刘汉清.液质联用技术分析延胡索中的生物碱类成分.中国医药导报,2008,5(11):48-49
[20]牟昀雅,余伯阳. HPLC/MS/MS法分离鉴定罗通定在大鼠胆汁中的代谢产物.中国天然药物,2007,4(6):448-451
[21]Kong L, Yu Z, Bao Y, Su X, Zou H, Li X. Screening and analysis of an antineoplastic compound inRhizoma Chuanxiong by means of in vitro metabolism and HPLC-MS. Analytical and bioanalyticalchemistry,2006,386(2):264-274
[1]Shi J, LU L. Traditional Chinese medicine in treatment of opiate addiction1. Acta pharmacologica sinica,2006,27(10):1303-1308
[2]Li L, Xing X, Shao H. Preparation of traditional Chinese herbs on addiction detoxification: recentprogress. Chin Med,2003,34(2):2012
[3]Xiong JG, Xiao ZX, Li J, Qin DS, Min MS, Yang JH, Wang YH, Yan L, Shu QL. Clinical effect of Jitaitablet combined with lofexidine in the treatment of heroin dependence. Chin. J. Drug Depend.2001,22(4):290–292
[4]Tu QX, Zhao HG, Cheng YP, Chen YM, Huang XP, Chen Y.M, Han M. Comparision study on clinicalefficacy of Jitai capsule with lofexidine in the treatment of opiate addicts. Chin. J. Drug Depend.1999,11(4):285–287
[5]Wang S, Liu L, Wang L, Jiang P, Zhang J, Zhang W, Liu R. Screening and analysis of the multipleabsorbed bioactive components and metabolites in rat plasma after oral administration of Jitai tablets byhigh performance liquid chromatography/diode array detection coupled with electrospray ionizationtandem mass spectrometry. Rapid Communications in Mass Spectrometry,24(11):1641-1652
[6]Wang L, Zhou GB, Liu P, Song JH, Liang Y, Yan XJ, Xu F, Wang BS, Mao JH, Shen ZX. Dissection ofmechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment forpromyelocytic leukemia. Proceedings of the National Academy of Sciences,2008,105(12):4826-4831
[7]Ling H, Wu L, Li L. Corydalis yanhusuo rhizoma extract reduces infarct size and improves heartfunction during myocardial ischemia/reperfusion by inhibiting apoptosis in rats. Phytotherapy research,2006,20(6):448-453
[8]Mantsch JR, Li SJ, Risinger R, Awad S, Katz E, Baker DA, Yang Z. Levo-tetrahydropalmatineattenuates cocaine self-administration and cocaine-induced reinstatement in rats. Psychopharmacology,2007,192(4):581-591
[9]Ding B, Zhou T, Fan G, Hong Z, Wu Y. Qualitative and quantitative determination of ten alkaloids intraditional Chinese medicine Corydalis yanhusuo WT Wang by LC-MS/MS and LC-DAD. Journal ofpharmaceutical and biomedical analysis,2007,45(2):219-226
[10]Ma ZZ, Xu W, Jensen NH, Roth BL, Liu Chen LY, Lee DY. Isoquinoline alkaloids isolated fromCorydalis yanhusuo and their binding affinities at the dopamine D1receptor. Molecules,2008,13(9):2303-2312
[11]Zhang J, Jin Y, Dong J, Xiao Y, Feng J, Xue X, Zhang X, Liang X. Systematic screening andcharacterization of tertiary and quaternary alkaloids from corydalis yanhusuo WT Wang usingultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Talanta,2009,78(2):513-522
[12]Shimizu T, Iwata S-i, Morioka H, Masuyama T, Fukuda T, Nomoto M. Antinociceptive mechanism ofL-DOPA. Pain,2004,110(1):246-249
[13]Wang JB, Mantsch JR. l-tetrahydropalamatine: a potential new medication for the treatment of cocaineaddiction. Future,4(2):177-186
[14]Xi ZX, Gilbert J, Campos AC, Kline N, Ashby CR, Hagan JJ, Heidbreder CA, Gardner EL. Blockade ofmesolimbic dopamine D3receptors inhibits stress-induced reinstatement of cocaine-seeking in rats.Psychopharmacology,2004,176(1):57-65
[15]Liu Y, Liang J, Yan L, Su R, Wu C, Gong Z. Effects of l-etrahydropalmatine on locomotor sensitizationto oxycodone in mice. Acta pharmacologica sinica,2005,26(5):533-538
[16]Chu H, Jin G, Friedman E, Zhen X. Recent development in studies of tetrahydroprotoberberines:mechanism in antinociception and drug addiction. Cellular and molecular neurobiology,2008,28(4):491-499
[17]Wang C, Wang S, Fan G, Zou H. Screening of antinociceptive components in Corydalis yanhusuo WTWang by comprehensive two-dimensional liquid chromatography/tandem mass spectrometry. Analyticaland bioanalytical chemistry,396(5):1731-1740
[18]Fan ZC, Xie CJ, Zhang ZQ. Simultaneous Quantitation of Tetrahydropalmatine and Protopine in RabbitPlasma by HPLC-DAD, and Application to Pharmacokinetic Studies. Chromatographia,2006,64(9):577-581
[19]Hong Z, Fan G, Le J, Chai Y, Yin X, Wu Y. Brain pharmacokinetics and tissue distribution oftetrahydropalmatine enantiomers in rats after oral administration of the racemate. Biopharmaceutics&drug disposition,2006,27(3):111-117
[20]Hong Z, Fan G, Chai Y, Yin X, Wen J, Wu Y. Chiral liquid chromatography resolution andstereoselective pharmacokinetic study of tetrahydropalmatine enantiomers in dogs. Journal ofchromatography B,2005,826(1):108-113
[21]He D, Chen B, Tian Q, Yao S. Simultaneous determination of five anthraquinones in medicinal plantsand pharmaceutical preparations by HPLC with fluorescence detection. Journal of pharmaceutical andbiomedical analysis,2009,49(4):1123-1127
[22]Matuszewski B, Constanzer M, Chavez-Eng C. Strategies for the assessment of matrix effect inquantitative bioanalytical methods based on HPLC-MS/MS. Analytical Chemistry,2003,75(13):3019-3030
[23]Yu S, Pang X, Deng Y, Liu L, Liang Y, Liu X, Xie L, Wang G, Wang X. A sensitive and specific liquidchromatography mass spectrometry method for simultaneous determination of berberine, palmatine,coptisine, epiberberine and jatrorrhizine from Coptidis Rhizoma in rat plasma. International Journal ofMass Spectrometry,2007,268(1):30-37
[24]Deng Y, Liao Q, Li S, Bi K, Pan B, Xie Z. Simultaneous determination of berberine, palmatine andjatrorrhizine by liquid chromatography tandem mass spectrometry in rat plasma and its application in apharmacokinetic study after oral administration of coptis vodia herb couple. Journal of chromatographyB,2008,863(2):195-205
[25]Zhou H. Pharmacokinetic strategies in deciphering atypical drug absorption profiles. The Journal ofClinical Pharmacology,2003,43(3):211-227
[26]Zhang XP, Li ZJ, Liu D-R. Progress in research into the mechanism of Radix salviae miltiorrhizae intreatment of acute pancreatitis. Hepatobiliary Pancreat Dis Int,2006,5(4):501-504
[27]Homma M, Oka K, Taniguchi C, Niitsuma T, Hayashi T. Systematic Analysis of Post administrativeSaiboku to Urine by Liquid Chromatography to Determine Pharmacokinetics of Traditional ChineseMedicine. Biomedical Chromatography,1998,11(3):125-131
[28]Fang XS, Hao J, Zhou H, Zhu L, Wang J, Song F. Pharmacological studies on the sedative-hypnoticeffect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen)extracts and the synergistic effect of their combinations. Phytomedicine,17(1):75-80
[29]Kinoshita K, Kawai T, Imaizumi T, Akita Y, Koyama K, Takahashi K. Anti-emetic principles of Inulalinariaefolia flowers and Forsythia suspensa fruits. Phytomedicine,1996,3(1):51-58
[30]Barone E, Calabrese V, Mancuso C. Ferulic acid and its therapeutic potential as a hormetin forage-related diseases. Biogerontology,2009,10(2):97-108
[31]Chueh WH, Lin JY. Berberine, an isoquinoline alkaloid in herbal plants, protects pancreatic islets andserum lipids in nonobese diabetic mice. Journal of agricultural and food chemistry,59(14):8021-8027
[32]Sun X, Wei X, Qu S, Zhao Y, Zhang X. Hydroxysafflor Yellow A suppresses thrombin generation andinflammatory responses following focal cerebral ischemia heperfusion in rats. Bioorganic&medicinalchemistry letters,20(14):4120-4124
[33]Zhan JY, Zheng KY, Zhu KY, Bi CW, Zhang WL, Du CY, Fu Q, Dong TT, Choi RC, Tsim KW.Chemical and biological assessment of Angelicae Sinensis Radix after processing with wine: anorthogonal array design to reveal the optimized conditions. Journal of agricultural and food chemistry,59(11):6091-6098
[34]Chang HK, Shin MS, Yang HY, Lee JW, Kim YS, Lee MH, Kim J, Kim KH, Kim CJ. Amygdalininduces apoptosis through regulation of Bax and Bcl-2expressions in human DU145and LNCaPprostate cancer cells. Biological and Pharmaceutical Bulletin,2006,29(8):1597-1602
[35]Rauws A, Olling M, Timmerman A. The pharmacokinetics of amygdalin. Archives of toxicology,1982,49(3):311-319
[36]Li X, Yu C, Cai Y, Liu G, Jia J, Wang Y. Simultaneous determination of six phenolic constituents ofdanshen in human serum using liquid chromatography/tandem mass spectrometry. Journal ofchromatography B,2005,820(1):41-47
[37]Zhou Q, Ding Y, Xiao J. Simultaneous determination of cyanazine, chlorotoluron and chlorbenzuron inenvironmental water samples with SPE multiwalled carbon nanotubes and LC. Chromatographia,2007,65(1):25-30
[38]Zhan Y, Xu J-P, Liang JB, Sheng LS, Xiang BR, Zou QG, Zhang ZJ. Simultaneous LC-MS/MS Analysisof Danshensu, Salvianolic Acid B, and Hydroxysafflor Yellow A in Beagle Dog Plasma, and Applicationof the Method to a Pharmacokinetic Study of Danhong Lyophilized Powder for Injection.Chromatographia,2008,68(1):71-79
[39]Guo X, Chen X, Li L, Shen Z, Wang X, Zheng P, Duan F, Ma Y, Bi K. LC-MS determination andpharmacokinetic study of six phenolic components in rat plasma after taking traditional Chinesemedicinal-preparation: Guanxinning lyophilized powder for injection. Journal of chromatography B2008,873(1):51-58
[40]Wen A, Yang J, Jia Y, Yang Z, Tian Y, Wu Y, Wang Z, He Z. A rapid and sensitive liquidchromatography tandem mass spectrometry (LC MS/MS) method for the determination ofhydroxysafflor yellow A in human plasma: Application to a pharmacokinetic study. Journal ofchromatography B,2008,876(1):41-46
[41]Chang J, Zhang Y. Catalytic Degradation of Amygdalin by Extracellular Enzymes from Aspergillusniger Process Biochemistry.
[42]Ge B, Chen H, Han F, Chen Y. Identification of amygdalin and its major metabolites in rat urine by LCMS/MS. Journal of Chromatography B,2007,857(2):281-286
[43]Jin Y, Zhang X, Shi H, Xiao Y, Ke Y, Xue X, Zhang F, Liang X. Characterization of Chlycosylquinochalcones in Carthamus tinctorius L. by ultraperformance liquid chromatography coupled withquadrupole time of flight mass spectrometry. Rapid Communications in Mass Spectrometry,2008,22(8):1275-1287
[44]Zhang T, Yang X, Zhang P, Zhu M, He Z, Bi K. Determination of Ferulic Acid in Rat Plasma by LiquidChromatography tandem Mass Spectrometry Method: Application to a Pharmacokinetic Study.Analytical Letters,2009,42(14):2157-2169
[45]Wen XD, Qi LW, Li P, Bao KD, Yan XW, Yi L, Li CY. Simultaneous determination ofcalycosin-7-O-beta-D-glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid in rat plasmaafter oral administration of Danggui Buxue Tang extract for their pharmacokinetic studies by liquidchromatography-mass spectrometry. J Chromatogr B,2008,865(1-2):99-105
[46]Zhan Y, Liang J, Sheng L, Xiang B, Zou Q, Zhang W, Xu J. Development and Validation of LiquidChromatography tandem Mass Spectrometry for Simultaneous Determination of the Four ActiveComponents of Danhong Freeze ried Powder Injection in Human Plasma. Analytical Letters,2008,41(5):737-756
[47]Liu Y, Li X, Li Y, Wang L, Xue M. Simultaneous determination of danshensu, rosmarinic acid,cryptotanshinone, tanshinone IIA, tanshinone I and dihydrotanshinone I by liquid chromatographicmass spectrometry and the application to pharmacokinetics in rats. Journal of pharmaceutical andbiomedical analysis,53(3):698-704
[48]Zhang YJ, Wu L, Zhang QL, Li J, Yin FX, Yuan Y. Pharmacokinetics of phenolic compounds ofDanshen extract in rat blood and brain by microdialysis sampling. Journal of ethnopharmacology,136(1):129-136
[49]Jin G, Xue X, Zhang F, Zhang X, Xu Q, Jin Y, Liang X. Prediction of retention times and peak shapeparameters of unknown compounds in traditional Chinese medicine under gradient conditions by ultraperformance liquid chromatography. Analytica Chimica Acta,2008,628(1):95-103
[50]Qi J, Jin X, Huang L, Ping Q. Simultaneous determination of hydroxysafflor yellow A and ferulic acidin rat plasma after oral administration of the co extractum of Rhizoma chuanxiong and Flos Carthami byHPLC diode array detector. Biomedical Chromatography,2007,21(8):816-822
[51]Liu AH, Guo H, Min Y, Lin YH, Sun J-H, Man X, Guo DA. Detection, characterization andidentification of phenolic acids in Danshen using high-performance liquid chromatography with diodearray detection and electrospray ionization mass spectrometry. Journal of chromatography B,2007,1161(1-2):170-182
[52]Wu YT, Chen YF, Hsieh YJ, Jaw I, Shiao MS, Tsai TH. Bioavailability of salvianolic acid B inconscious and freely moving rats. International journal of pharmaceutics,2006,326(1):25-31
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |