冬凌草乙素在Beagle犬体内的药代动力学研究
摘要
背景：
冬凌草乙素作为冬凌草的抗肿瘤有效成分,已有研究表明其具有显著的抗血管原活性,能显著抑制人骨髓瘤细胞、肝癌细胞的增殖并诱导凋亡,更有效地抑制乳腺癌细胞的生成和增殖。这些研究表明,冬凌草乙素有望成为一种天然的抗肿瘤新药。但到目前为止,尚未见有关用高效液相法测定Beagle犬血浆中冬凌草乙素的浓度,以及报道其在Beagle犬体内的药动学特征。
目的：
本文旨在建立一种专属性强、操作简便的高效液相色谱检测方法,用来测定Beagle犬血浆中冬凌草乙素的浓度,阐明冬凌草乙素静脉注射后在Beagle犬体内的药代动力学特性,为冬凌草乙素进一步的开发利用提供依据。
方法：
500μL含冬凌草乙素的Beagle犬血浆样品中加入20μL内标非那西丁,经乙酸乙酯萃取处理后,以甲醇-0.5%三乙胺(34：66,v/v)为流动相,流速为1mL/min,进样量：20μL。采用C18柱分离,紫外检测器检测,最大吸收波长为232nm。
结果：
冬凌草乙素在50.0～4000ng/mL的范围内呈良好的线性关系(r2=0.9995),最低定量限达50.0ng/mL。样品在血浆中的提取回收率大于80%,日内和日间的RSD均小于10%,符合生物样品分析要求。血浆样品预处理操作简便,且内源性物质不干扰测定。将所得冬凌草乙素在犬体内的血药浓度-时间数据,用3P97软件拟合,以AIC值为拟合度指标确定所采用的房室模型,并求算冬凌草乙素在犬体内的各项药代动力学参数。
结论：
本文首次建立了Beagle犬血浆中冬凌草乙素的高效液相色谱分析方法。本文所建立的定量分析方法快速、灵敏、易操作,成功的用于冬凌草乙素在Beagle犬体内的药物动力学研究。
Background:
Ponicidin is one of the major anti-tumor constituents of Rabdosia rubescens. Studies have shown that it has significant anti-angiogenic activity of the original. Laboratory data have also shown that ponicidin can significantly inhibit the human myeloma cell, liver cell proliferation and induce apoptosis, more effectively inhibit thegeneration and proliferation of breast cancer cells. These studies indicate that ponicidin is expected to become a natural anti-tumor drugs. But so far, the concentration of ponicidin has not been measured in the Beagle dog plasma with HPLC, and no information about the pharmacokinetic characteristics of it in Beagle dog was reported.
Objective:
This article aims to establish a specific, simple high-performance liquid chromatography method used to determine the concentration of ponicidin in the Beagle dog plasma, and to clarify the pharmacokinetic characteristics of ponicidin in Beagle dog after the intravenous injection. These studies provide a basis for further development and utilization on ponicidin.
Method:
500μL Beagle dog plasma samples containing ponicidin, added20μL phenacetin solution as the internal, was extracted by ethyl acetate. An C18column was used to separate ponicidin in plasma with methanol-0.5%triethylamine (34:66,v/v) as mobile phase, at a flow rate of1mL/min,injection volume:20μL. Uvdetector was used and the maximun absorption wavelength was set at232nm.
Results:
Ponicidin in the range50.0～4000ng/mL showed a good linear relationship (r2=0.9995), and the lowest limit of quantification (LLOQ) achieved was50.0ng/mL. The extraction recoveries of sample in the plasma were greater than80%, and the intra-and inter-day precision were less than10.0%, in line with biological sample analysis requirements. Plasma sample preparation was simple and did not interfere with the determination of the endogenous substances. The plasma concentration-time data obtained in dogs, fitted with3P97software to AIC as a goodness of fit index was used to determine the compartment model and calculate the pharmacokinetic parameters.
Conclusion:
The HPLC method was established for the first time to analyze ponicidin in Beagle dog plasma. This quantitative analysis method established was rapid, sensitive, easy to operate. The method was successfully used to study the pharmacokinectic of ponicidin in Beagle dog plasma.
冬凌草乙素作为冬凌草的抗肿瘤有效成分,已有研究表明其具有显著的抗血管原活性,能显著抑制人骨髓瘤细胞、肝癌细胞的增殖并诱导凋亡,更有效地抑制乳腺癌细胞的生成和增殖。这些研究表明,冬凌草乙素有望成为一种天然的抗肿瘤新药。但到目前为止,尚未见有关用高效液相法测定Beagle犬血浆中冬凌草乙素的浓度,以及报道其在Beagle犬体内的药动学特征。
目的：
本文旨在建立一种专属性强、操作简便的高效液相色谱检测方法,用来测定Beagle犬血浆中冬凌草乙素的浓度,阐明冬凌草乙素静脉注射后在Beagle犬体内的药代动力学特性,为冬凌草乙素进一步的开发利用提供依据。
方法：
500μL含冬凌草乙素的Beagle犬血浆样品中加入20μL内标非那西丁,经乙酸乙酯萃取处理后,以甲醇-0.5%三乙胺(34：66,v/v)为流动相,流速为1mL/min,进样量：20μL。采用C18柱分离,紫外检测器检测,最大吸收波长为232nm。
结果：
冬凌草乙素在50.0～4000ng/mL的范围内呈良好的线性关系(r2=0.9995),最低定量限达50.0ng/mL。样品在血浆中的提取回收率大于80%,日内和日间的RSD均小于10%,符合生物样品分析要求。血浆样品预处理操作简便,且内源性物质不干扰测定。将所得冬凌草乙素在犬体内的血药浓度-时间数据,用3P97软件拟合,以AIC值为拟合度指标确定所采用的房室模型,并求算冬凌草乙素在犬体内的各项药代动力学参数。
结论：
本文首次建立了Beagle犬血浆中冬凌草乙素的高效液相色谱分析方法。本文所建立的定量分析方法快速、灵敏、易操作,成功的用于冬凌草乙素在Beagle犬体内的药物动力学研究。
Background:
Ponicidin is one of the major anti-tumor constituents of Rabdosia rubescens. Studies have shown that it has significant anti-angiogenic activity of the original. Laboratory data have also shown that ponicidin can significantly inhibit the human myeloma cell, liver cell proliferation and induce apoptosis, more effectively inhibit thegeneration and proliferation of breast cancer cells. These studies indicate that ponicidin is expected to become a natural anti-tumor drugs. But so far, the concentration of ponicidin has not been measured in the Beagle dog plasma with HPLC, and no information about the pharmacokinetic characteristics of it in Beagle dog was reported.
Objective:
This article aims to establish a specific, simple high-performance liquid chromatography method used to determine the concentration of ponicidin in the Beagle dog plasma, and to clarify the pharmacokinetic characteristics of ponicidin in Beagle dog after the intravenous injection. These studies provide a basis for further development and utilization on ponicidin.
Method:
500μL Beagle dog plasma samples containing ponicidin, added20μL phenacetin solution as the internal, was extracted by ethyl acetate. An C18column was used to separate ponicidin in plasma with methanol-0.5%triethylamine (34:66,v/v) as mobile phase, at a flow rate of1mL/min,injection volume:20μL. Uvdetector was used and the maximun absorption wavelength was set at232nm.
Results:
Ponicidin in the range50.0～4000ng/mL showed a good linear relationship (r2=0.9995), and the lowest limit of quantification (LLOQ) achieved was50.0ng/mL. The extraction recoveries of sample in the plasma were greater than80%, and the intra-and inter-day precision were less than10.0%, in line with biological sample analysis requirements. Plasma sample preparation was simple and did not interfere with the determination of the endogenous substances. The plasma concentration-time data obtained in dogs, fitted with3P97software to AIC as a goodness of fit index was used to determine the compartment model and calculate the pharmacokinetic parameters.
Conclusion:
The HPLC method was established for the first time to analyze ponicidin in Beagle dog plasma. This quantitative analysis method established was rapid, sensitive, easy to operate. The method was successfully used to study the pharmacokinectic of ponicidin in Beagle dog plasma.
引文
[1]田红.靶向抗肿瘤药物的研究进展[J].世界临床药物,2008,(29)：494-501
[2]马彦.长春碱类抗肿瘤药物的研究进展[J].中山大学研究生学刊(自然科学、医学版),2004,(25)：31-39
[3]马振伟.抗肿瘤植物药的应用进展[J].医药导报,2006,25(12)：1303-1305
[4]申向黎,张伶俐.天然抗肿瘤药物的发展趋势[J].中国药业,2007,16(21)：63-64
[5]顾琳娜,顾昊.天然抗肿瘤药物筛选方法的研究进展[J].医药导报,2009,28(4)：496-498
[6]王君明,崔瑛.天然抗肿瘤药物筛选方法研究进展[J].时珍国医国药,2011,22(8)：1994-1995
[7]韩全斌,梅双喜,姜北,等.冬凌草中的新对映一贝壳杉烷二萜化合物[J].有机化学,2003,23(3)：270-273
[8]杨延武,浒肖龙,何炳林2D-NMR方法研究抗癌药物冬凌草乙素的结构与谱线归属[J].高等学校化学学报,1993,14(5)：733-737
[9]张覃沐,陈正玉,赵清治,等.冬凌草中又一抗肿瘤有效成分[J].科学通报,1980,(22)：1051-1054
[10]寇娴,张雁冰,王桂红,等.冬凌草乙素-β-环糊精包合物的研究[J].郑州大学学报(自然科学版),1998,30(30)：64-66
[11]闫学斌,雷萌,可钰,等.冬凌草的化学成分研究[J].化学研究,2006,17(13)：80-82
[12]卢海英,梁敬钰,陈荣.冬凌草的化学成分[J].中国天然药物,2007,5(4)：269-271
[13]左海军,李丹,吴斌,等.冬凌草的化学成分及其抗肿瘤活性[J].沈阳药科大学学报,2005,22(4)：258-261
[14]尹锋,梁敬钰,刘净.冬凌草化学成分的研究[J].中国药科大学学报,2003,34(4)：302-304
[15]Lu Y, Sun C, Liu R, et al. Effective two-dimensional countercurrent chromatographic method for simultaneous isolation and purification of oridonin and ponicidin from the crude extract of Rabdosia rubescens[J]. J Chromatogr A,2007,1146 (1):125～130
[16]金珠,周丽莉.高效液相色谱法测定冬凌草中冬凌草甲素及冬凌草乙素的含量[J].时珍国医国药,2004,15(6)：321-322
[17]袁珂,吴崇珍,张晓明,等.高效液相色谱法同时测定冬凌草中冬凌草甲、乙素的含量[J].中国现代应用药学杂志,2004,21(3)：213-215
[18]孙冬云HPLC法测定冬麦利咽口服液中冬凌草甲素和冬凌草乙素的含量[J].中国中医药现代远程教育,2011,9(9)：155-156
[19]张静,袁珂,金永春,等UPLC法同时测定冬凌草中5种有效成分的含量[J].药物 分析杂志,2011,31(4)：641-644
[20]袁珂,胡润淮,杨怡,等.TLC测定冬凌草中冬凌草甲、乙素的含量[J].中国药学杂志,1998,33(10)：611
[21]杨中汉,田京城.冬凌草叶中冬凌草甲、乙素的含量测定[J].河南工业大学学报(自然科学版),2005,26(4)：53-55
[22]Yiran Jin. Yingfeng Du, Xiaowei Shi, et al. Simultaneous quantification of 19 diterpenoids in Isodon amethystoides by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry[J]. Journal of Pharmaceutical and Biomedical Analysis,2010,53:403～411
[23]Xiaotian Li, Wenjing Hou, Jingjing Song, et al. A simple and sensitive HPLC-UV method for the determination of ponicidin in rat plasma and its application in a pharmacokinetic study[J]. Biomedical Chromatography,2011,25:362～366
[24]贾欣,高岩,杜斌,等HPCE法测定冬凌草片中冬凌草甲素的含量[J].郑州大学学报(医学版),2006,41(1)：156-157
[25]Fujita E, Nagao Y, Kaneko K, et al. The anti tumor and antibacterial activity of the Isodon diterpenoids[J].Chem Pharm Bull,1976,24 (9):2118～2127
[26]Fujita E, Nagao Y, Kohno T, et al. Antitumor activity of acylated Oridonin[J]. Chem Pharm Bull,1981,29 (11):3208～3213
[27]张覃沐,陈正玉,赵清治,等.冬凌草中又一抗肿瘤有效成分[J].科学通报,1980,(22)：1051-1054
[28]Chung-Hang Leung, Susan P. Grill, Wing Lam, et al. Novel Mechanism of Inhibition of Nuclear Factor-κB DNA-Binding Activity by Diterpenoids Isolated from Isodon rubescens [J]. Molecular Pharmacology,2005,68:286-297
[29]Liu J J, Huang R W, Lin D J, et al. Ponicidin. an ent-kaurane diterpenoid derived from a constituent of the herbal supplement PC-SPES, Rabdosia rubescens, induces apoptosis by activation of caspase-3 and mitochondrial events in lung cancel-cells in Vitro [J]. Cancer Invest,2006,24 (2):136～148
[30]刘晓丹,刘文达,王春芝,等.冬凌草乙素对白血病HL-60细胞的增殖抑制作用[J].中国组织工程研究与临床康复,2010,14(27)：5062-5066
[31]刘晓丹,刘文达,王春芝,等.冬凌草乙素对白血病NB4细胞的体外诱导凋亡作用研究[J].中华肿瘤防治杂志,2010,17(12)：894-898
[32]Liu J J, Huang R W, Lin D J, et al. Antiproliferation effects of ponicidin on human myeloid leukemia cells in vitro[J]. Oncol Rep,2005,13 (4):653～657
[33]Tze-chen Hsieh, E. Kithsiri Wijeratne, Jing-yu Liang, et al. Differential control of growth, cell cycle progression, and expression of NF-κB in human breast cancer cells MCF-7, MCF-10A, and MDA-MB-231 by ponicidin and oridonin, diterpenoids from the Chinese herb Rabdosia rubescens [J]. Biochemical Biophysical Research Communications,2005, 337 (1):224-231
[34]J.-F. Zhang, P.-Q. Liu, G.-H. Chen, et al. Ponicidin inhibits cell growth on hepatocellular carcinoma cells by induction of apoptosis [J]. Digestive and Liver Disease,2007,39 (2): 160～166
[35]薛宏伟,潘祥麟.冬凌草乙素诱导GBC-SD细胞的凋亡及对Bcl-2、p53 Fas/APO-1、 C-myc表达的影响[J].中国药理学通报,2003,19(11)：1247-1251
[36]王筠,戈士文,王毅,等.几种香茶菜属二萜类化合物的抗氧化作用[J].中国药理学通报,2003,19(9)：1009-1012
[37]张覃沐,陈正玉,林晨,等.冬凌草乙素药理作用之研究[J].河南医学院学报,1979,(1)：10-14
[38]Babiker M. El-Haj, Abdelkader M. Al-Amri and Heyam S. Ali. GC-MS detection and tentative characterization of two noscapine metabolites in human urine and their potential as markers for opium and illicit heroin use [J]. Forensic Toxicology,2007,25:22～29
[39]Ioannis Papoutsis, Panagiota Nikolaou, Artemisia Dona, et al. A validated GC-MS method for the determination of A9-tetrahydrocannabinol and 11-nor-△9-tetrahydrocannabinol-9-carboxylic acid in bile samples [J]. Forensic Toxicology,2012,30:51～58
[40]Veniero Gambaro, Claudio Benvenuti, Lucia De Ferrari, et al. Validation of a GC/MS method for the determination of tramadol in human plasma after intravenous bolus [J]. Il Farmaco,2003,58:947～950
[41]S. Magiera, C. Uhlschmied, M. Rainer, et al. GC-MS method for the simultaneous determination of P-blockers, flavonoids, isoflavones and their metabolites in human urine [J]. Journal of Pharmaceutical and Biomedical Analysis,2011,56:93～102
[42]Huang Ping, Jiang Xiaofei, Zou Jiali, et al. A Novel GC-MS Bioanalytical Method for Natural Borneol and Its Application in Investigating Natural Borneol Distribution in Mice [J]. World Science and Technology,2009,11:821～827
[43]Jing Chen, Kalpana S. Paudel, Andrei V. Derbenev, et al. Simultaneous Quantification of Anandamide and Other Endocannabinoids in Dorsal Vagal Complex of Rat Brainstem by LC-MS[J].Chromatographia,2009,69:1～7
[44]Jing Zhang, Hao-Jing Song, Fan-Long Bu, et al.Determination of nifedipine concentration in human plasma by LC-MS and its application in pharmacokinetic study [J]. Journal of Chinese Pharmaceutical Sciences,2010,19:471～476
[45]Lin-lin Chen, Wei-wei Yuan, Zheng-fang Hu, et al. Determination and pharmacokinetics of DT-13 in rat plasma by LC-MS [J]. Journal of Pharmaceutical and Biomedical Analysis, 2011,56:650～654
[46]R. Nageswara Rao, Dhananjay D. Shinde, M. V. N. Kumar Talluri, et al. LC-ESI-MS determination and pharmacokinetics of adrafinil in rats[J]. Journal of Chromatography B, 2008,873:119～123
[47]Jeovanis Gil, Ania Cabrales, Osvaldo Reyes, et al.Development and validation of a bioanalytical LC-MS method for the quantification of GHRP-6 in human plasma[J]. Journal of Pharmaceutical and Biomedical Analysis,2012,60:19～25
[48]C. Webber, C. A. Stokes, S. Persiani, et al. Absorption, distribution, metabolism and excretion of the cholecystokinin-1 antagonist dexloxiglumide in the dog [J]. European Journal of Drug Metabolism and Pharmacokinetics,2004,29:15～23
[49]司倩,陈渊成,黄黎华,等LC-MS/MS法测定人血浆中奈比洛尔浓度及其在中国人体内的药代动力学[J].中国药科大学学报,2011,42(2)：136-140
[50]Michael T. Furlong, Shruti Agrawal, Dara Hawthorne, et al. A validated LC-MS/MS assay for the simultaneous determination of the anti-leukemic agent dasatinib and two pharmacologically active metabolites in human plasma:Application to a clinical pharmacokinetic study[J]. Journal of Pharmaceutical and Biomedical Analysis,2012,58: 130～135
[51]Olivier Heudi, Samuel Barteau, Franck Picard, et al. A sensitive LC-MS/MS method for quantification of a nucleoside analog in plasma:Application to in vivo rat pharmacokinetic studies [J]. Journal of Chromatography B,2009,877:1887～1893
[52]Rodolpho C. Braga, Andrea C. B. Torres, Camille B. Persiano, et al. Determination of the cardioactive prototype LASSBio-294 and its metabolites in dog plasma by LC-MS/MS: Application for a pharmacokinetic study [J]. Journal of Pharmaceutical and Biomedical Analysis,2011,55:1024～1030
[53]Isam I. Salem, Musab Alkhatib, Naji Najib. LC-MS/MS determination of betamethasone and its phosphate and acetate esters in human plasma after sample stabilization [J]. Journal of Pharmaceutical and Biomedical Analysis,2011,56:983～991
[54]Raymond Naxing Xu, Leimin Fan, Matthew J. Rieser, et al. Recent advances in high-throughput quantitative bioanalysis by LC-MS/MS [J]. Journal of Pharmaceutical and Biomedical Analysis,2007,44:342～355
[55]Alfonso Espada, Manuel Molina-Martin, Jeffrey Dage, et al. Application of LC/MS and related techniques to high-throughput drug discovery [J]. Drug Discovery Today,2008,13: 417-423
[56]Ian D. Wilson, J.K. Nicholson. Solid phase extraction chromatography and NMR spectroscopy (SPEC-NMR) for the rapid identification of drug metabolites in urine [J]. Journal of Pharmaceutical and Biomedical Analysis,1988,6:151～165
[57]Farida Y. K. Ghauri, Andre E. M. McLean, Denis Beales, et al. Induction of 5-oxoprolinuria in the rat following chronic feeding with N-acetyl 4-aminophenol (paracetamol)[J]. Biochemical Pharmacology,1993,46:953～957
[58]Klaus Albert, Ernst Bayer. High-performance liquid chromatography-nuclear magnetic resonance on-line coupling [J]. TrAC Trends in Analytical Chemistry,1988,7:288～293
[59]John C Lindon, Jeremy K Nicholson, Ian D Wilson. Directly coupled HPLC-NMR and HPLC-NMR-MS in pharmaceutical research and development [J]. Journal of Chromatography B:Biomedical Sciences and Applications,2000,748:233～258
[60]Vlassios Goulas, Ana Maria Gomez-Caravaca, Vassiliki Exarchou, et al. Exploring the antioxidant potential of Teucrium polium extracts by HPLC-SPE-NMR and on-line radical-scavenging activity detection [J]. LWT-Food Science and Technology,2012,46: 104～109
[61]辛普森C F.实用高效液相色谱法.徐征帆译.北京：中国建筑出版社,1981,2
[62]Lukas Kaminski, Matthias Degenhardt. Joachim Ermer, et al. Efficient and economic HPLC performance qualification [J]. Journal of Pharmaceutical and Biomedical Analysis,2010, 51:557-564
[63]Kallol M. Biswas, Bryan C. Castle, Bernard A. Olsen, et al. A simple and efficient approach to reversed-phase HPLC method screening [J]. Journal of Pharmaceutical and Biomedical Analysis,2009,49:692～701
[64]杜斌,张振中.现代色谱技术[M].郑州：郑州大学出版社,2002,124
[65]Xia J H. Validation of bio-analytical methods for Pharmacokinetics, bioavailability and Bioequivalence studies [J]. Asian J Drug Metab Pharmacokinet,2001,1 (20):95～100
[66]Jian Ge, Wang You-Wei, Lu Xiao-Cong, et al. Determination of oridonin in rat plasma by reverse phase high-performance liquid chromatography [J]. Journal of Pharmaceutical and Biomedical Analysis,2007,43:793～797
[67]Yinghao Mei, Jie Xu, Jihui Zhao, et al. An HPLC method for determination of oridonin in rabbits using isopsoralen as an internal standard and its application to pharmacokinetic studies for oridonin-loaded nanoparticles [J]. Journal of Chromatography B,2008,869: 138～141
[68]Lei Gao, Dianrui Zhang, Minghui Chen, et al. Studies on pharmacokinetics and tissue distribution of oridonin nanosuspensions [J]. International Journal of Pharmaceutics,2008, 355:321～327
[69]刘德文,张毅,李德凤,等.8-乙酰哈巴苷大鼠体内药代动力学[J].中国实验方剂学杂志,2011,17(20)：129-132
[70]黄敏文,王广基,孙建国,等RP-HPLC法测定Beagle犬血浆中烟酸浓度及烟酸药代动力学研究[J].中国临床药理学与治疗学,2005,10(3)：302-305
[71]Ioannis Niopas, Athanasios C. Daftsios. A validated high-performance liquid chromatographic method for the determination of glibenclamide in human plasma and its application to pharmacokinetic studies [J]. Journal of Pharmaceutical and Biomedical Analysis,2002,28:653～657
[72]刘振胜,赵艳,闫美兴,等HPLC法测定盐酸氟桂利嗪分散片的血药浓度及药动学研究[J].中国新药杂志,2005,14(8)：1041-1044
[73]Vinod P. Shah, Kamal K. Midha, John W. A. Findlay, et al. Bioanalytical Method Validation-A Revisit with a Decade of Progress [J]. Pharmaceutical Research,2000,17: 1551～1557
[74]张剑萍,郭澄.生物样品分析中的方法学验证[J].中国药房,2008,19(31)：2469-2471
[75]李好枝主编.体内药物分析[M].北京：人民卫生出版社2008,58
[76]Maria Toth, Andrea Bereczki, Sandor Drabant, et al. Gas chromatography nitrogen phosphorous detection (GC-NPD) assay of tofisopam in human plasma for pharmacokinetic evaluation [J]. Journal of Pharmaceutical and Biomedical Analysis,2006,41:1354～1359
[77]Vikneswaran Murugaiyah, Kit Lam Chan. Analysis of lignans from Phyllanthus niruri L. in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic study [J]. Journal of Chromatography B,2007,852:138～144
[78]Fawzy Elbarbry, Ahmed Attia, Ahmed Shoker. Validation of a new HPLC method for determination of midazolam and its metabolites:Application to determine its pharmacokinetics in human and measure hepatic CYP3A activity in rabbits [J]. Journal of Pharmaceutical and Biomedical Analysis,2009,50:987-993
[79]Sicen Wang, Qinhua Chen, Langchong He. Development and validation of a gas chromatography-mass spectrometry method for the determination of isoimperatorin in rat plasma and tissue:Application to the pharmacokinetic and tissue distribution study[J]. Journal of Chromatography B,2007,852:473-478
[80]Shaoying Hou, Fang Wang, Yingmei Li. Pharmacokinetic study of mangiferin in human plasma after oral administration [J]. Food Chemistry,2009,50:987～993
[81]孙毓庆主编.现代色谱法及其在药物分析中的应用.第一版.北京：科学出版社,2005：72
[82]王敏智,王兴,王萍.色谱技术在中药药动学研究中的应用进展[J].时珍国医国药,2010,21(11)：2971-2973
[83]李海生,白海娇.高效液相色谱应用中的若干问题与解决方法[J].天津药学,2006,18(2)：5-7
[84]刘昌孝主编.实用药物动力学.第一版.北京：中国医药科技出版社,2003：335
[85]闻俊.生物样品高通量液相色谱分析方法学研究及其药代动力学应用[D].[博士学位论文].上海：第二军医大学,2008
[86]张君仁,臧恒昌主编.体内药物分析.第一版.北京：化学工业出版社,2003：43
[87]李发美主编.医药高效液相色谱技术.北京：人民卫生出版社,1999：56
[88]宁宇,赵培荣,连小珂,等.反相高效液相色谱法测定人体血浆中冬凌草甲素含量[J].肿瘤基础与临床,2006,19(3)：180-182
[89]张典瑞,任天池,娄红祥,等.冬凌草甲素固态类脂纳米粒在小鼠体内的组织分布及兔体内的药代动力学[J].药学学报,2005,40(6)：573-576
[90]Yingfeng Du, Pengwei Liu, Xiaowei Shi, et al. A novel analysis method for diterpenoids in rat plasma by liquid chromatography-electrospray ionization mass spectrometry [J]. Analytical Biochemistry,2010,407:111～119
[91]杨桂芹,房世红,董欣,等LC-MS法测定犬血浆中冬凌草甲素含量[J].药物分析杂志,2011,31(5)：912-916
[92]顾轶,王广基,孙建国HPLC-MS测定Beagle犬血浆中非洛地平的浓度[J].华西药学杂志,2006,21(4)：372-374
[93]王萍,陈醒言,邱相君,等.高效液相色谱法测定健康人血浆中舍曲林浓度[J].中国临床药理学杂志,2006,22(99)：69-72
[94]邓泮,段小涛,陈笑艳,等.液相色谱-串联质谱法测定犬血浆中布地奈德[J].药学学报,2008,43(1)：76-80
[95]吴民淑,王广基,蔡晓辉,等.液相色谱-质谱联用法测定犬血浆中盐酸关附甲素的血药浓度及其药代动力学[J].药学学报,2002,37(7)：551-554
[96]何秀琼,裴利霞,王一涛,等.高效液相色谱法研究大鼠灌胃黄芩素的药动学[J].中国医院药学杂志,2010,30(22)：1901-1905
[97]吕晶,黄熙,段重高,等.胡黄连苷-Ⅰ在大鼠和犬体内药动学研究[J].解放军药学学报,2005,21(1)：1-3
[98]毛惠英,张丹,李鑫楠,等RP-HPLC测定家兔血浆中的儿茶素和表儿茶素[J].华西药学杂志,2009,24(1)：66-67
[99]汤南,张丹,孙文霞,等.丹参酮ⅡA磺酸钠在家兔体内的药代动力学研究药物分析杂志,2009,29(5)：760-763
[100]张凤霞, 贾振华,戴伟东,等.中药通心络对抑郁-动脉粥样硬化大鼠干预作用的血浆代谢组学研究[J].中国科学,2010,40(6)：725-732
[101]戴伟东,张凤霞,贾振华,等.基于液相色谱-质谱联用技术的代谢组学方法用于中药通心络和人参对过度疲劳大鼠干预作用的评价[J].色谱2011,29(11)：1049-1054
[102]樊惠远,赵清治,王汉清,等.冬凌草乙素的化学研究[J].河南医学院学报,1979,(1)：14-16
[103]寇娴,张雁冰,王桂红,等.冬凌草乙素-p-环糊精包合物的研究[J].郑州大学学报(自然科学版),1998,30(30)：64-66
[104]FDA. Guidance for Indust-Bioanalytical Method Validation [Z].2001 http //www/fda.gov/cder/guidance/index.htm.
[105]国家食品药品监督管理局药品审评中心.化学药物非临床药代动力学研究技术指导原则[M].2005.
[1]Xu Zhu, YaXin Sun, XiaoJing He, et al. HPLC-UV method with solidphase extraction for the quantitative determination of biapenem in human plasma and its application in pharmacokinetic study[J]. Journal of Chinese Pharmaceutical Sciences 2011,20:70～76
[2]Ding Jinsong, Zhang Bikui, Li Huande, Liu Yizhao and Deng Hang. HPLC Determination of Captopril in Human Plasma with Pre-column Derivation and Solid-phase Extraction and Studies on Its Pharmacokinetic and Relative Bioavailability [J]. Journal of Chinese Pharmaceutical Sciences 2001,10 (3):152～156
[3]李珍,唐世新,张晋萍,等.固相萃取-高效液相色谱法测定人血浆中吡格列酮浓度[J].中国医院药学杂志,2003,23(11)：653-655
[4]李智平,钟明康,施孝金,等.固相萃取-高效液相色谱法测定人血浆中硝苯地平浓度[J].中国临床药学杂志,2005,14(2)：115-117
[5]陈昆,王静,王睿,等.固相萃取HPLC检测生物样品中的甲苯磺丁脲和代谢产物及其人体药代动力学研究[J].药物分析杂志,2005,25(3)：50
[6]张颖.生物样品预处理技术及应用进展[J].天津药学,2006,18(1)：57
[7]Jeff Wise, Terry Danielson, Ashraf Mozayani, et al. Analysis of amphetamine, methamphetamine, methylenedioxyamphetamine and methylenedioxymethamphetamine in whole blood using in-matrix ethyl chloroformate derivatization and automated headspace solid-phase microextraction followed by GC-MS[J]. Forensic Toxicol,2008 (26):66～ 70
[8]Satt erfield M, Black D M, Brodbelt J S. Detect ion of the isoflavone aglycones genist ein and daidzein inurine using sol id-phase microextract ion high performance liquid chromatography-electrospray ionizat ion mass spectrometry[J]. J Chromatogr B Biomed Sci Appl,2001,759 (1):33
[9]Marcin Wasowicz, Angela Jerath, Barbara Bojko, et al. Use of a novel technique, solid phase microextraction, to measure tranexamic acid in patients undergoing cardiac surgery [J]. Canadian Journal of Anesthesia,2012, (59):14～20
[10]Klime J, Sochor J, Kriz J. A study of the conditions of the supercritical fluid extraction in the analysis of selected ant i-inflammatory drugs in plasma [J]. Faracp,2002,57 (2): 117
[11]Allen D L, Scott K S, Oliver J S. Comparison of solidphase ex tractio n and supercritical fluid extraction for the analy sis of mor phine in w hole blood[J]. J Anal Tox ical,1999, 23 (3):216～221
[12]Long-Hu Wang, Yan-Hong Mei, Feng Wang, et al. A novel and efficient method combining SFE and liquid-liquid extraction for separation of coumarins from Angelica dahurica[J]. Separation and Purification Technology,2011,77:397～401
[13]Xue Y J, Liu J, Unger S. A 96-well single-pot liquid-liquid extraction, hydrophilic interaction liquid chromatography-mass spectrometry method for the determination of muraglitazar in human plasma [J]. J Pharm Biomed Anal,2006,41 (3):979～988
[14]Wen Zhang, Xuni Cao, Yunfeng Xie, et al. Simultaneous determination of the monoamine neurotransmitters and glucose in rat brain by microdialysissampling coupled with liquid chromatography-dual electrochemical detector [J]. Journal of Chromatography B,2003, 785:327-336
[15]Anita L Freed, Josh D Cooper, Malonne Ⅰ Davies, et al. Investigation of the metabolism of substance P in rat striatum by microdialysissampling and capillary electrophoresis with laser-induced fluorescence detection [J]. Journal of Microbiological Methods,2003,109: 23～29
[16]Gang Cao, Hao Cai, Yun Zhang, et al. Identification of metabolites of crude and processed Fructus Corni in rats by microdialysissampling coupled with electrospray ionization linear quadrupole ion trap mass spectrometry [J]. Journal of Pharmaceutical and Biomedical Analysis,2011,56:118～125
[17]Xiaoping Ao, Robert F. Rotundo, Daniel J. Loegering, et al. In vivo microdialysissampling of cytokines produced in mice given bacterial lipopolysaccharide[J]. Journal of Microbiological Methods,2005,62:327～336
[2]马彦.长春碱类抗肿瘤药物的研究进展[J].中山大学研究生学刊(自然科学、医学版),2004,(25)：31-39
[3]马振伟.抗肿瘤植物药的应用进展[J].医药导报,2006,25(12)：1303-1305
[4]申向黎,张伶俐.天然抗肿瘤药物的发展趋势[J].中国药业,2007,16(21)：63-64
[5]顾琳娜,顾昊.天然抗肿瘤药物筛选方法的研究进展[J].医药导报,2009,28(4)：496-498
[6]王君明,崔瑛.天然抗肿瘤药物筛选方法研究进展[J].时珍国医国药,2011,22(8)：1994-1995
[7]韩全斌,梅双喜,姜北,等.冬凌草中的新对映一贝壳杉烷二萜化合物[J].有机化学,2003,23(3)：270-273
[8]杨延武,浒肖龙,何炳林2D-NMR方法研究抗癌药物冬凌草乙素的结构与谱线归属[J].高等学校化学学报,1993,14(5)：733-737
[9]张覃沐,陈正玉,赵清治,等.冬凌草中又一抗肿瘤有效成分[J].科学通报,1980,(22)：1051-1054
[10]寇娴,张雁冰,王桂红,等.冬凌草乙素-β-环糊精包合物的研究[J].郑州大学学报(自然科学版),1998,30(30)：64-66
[11]闫学斌,雷萌,可钰,等.冬凌草的化学成分研究[J].化学研究,2006,17(13)：80-82
[12]卢海英,梁敬钰,陈荣.冬凌草的化学成分[J].中国天然药物,2007,5(4)：269-271
[13]左海军,李丹,吴斌,等.冬凌草的化学成分及其抗肿瘤活性[J].沈阳药科大学学报,2005,22(4)：258-261
[14]尹锋,梁敬钰,刘净.冬凌草化学成分的研究[J].中国药科大学学报,2003,34(4)：302-304
[15]Lu Y, Sun C, Liu R, et al. Effective two-dimensional countercurrent chromatographic method for simultaneous isolation and purification of oridonin and ponicidin from the crude extract of Rabdosia rubescens[J]. J Chromatogr A,2007,1146 (1):125～130
[16]金珠,周丽莉.高效液相色谱法测定冬凌草中冬凌草甲素及冬凌草乙素的含量[J].时珍国医国药,2004,15(6)：321-322
[17]袁珂,吴崇珍,张晓明,等.高效液相色谱法同时测定冬凌草中冬凌草甲、乙素的含量[J].中国现代应用药学杂志,2004,21(3)：213-215
[18]孙冬云HPLC法测定冬麦利咽口服液中冬凌草甲素和冬凌草乙素的含量[J].中国中医药现代远程教育,2011,9(9)：155-156
[19]张静,袁珂,金永春,等UPLC法同时测定冬凌草中5种有效成分的含量[J].药物 分析杂志,2011,31(4)：641-644
[20]袁珂,胡润淮,杨怡,等.TLC测定冬凌草中冬凌草甲、乙素的含量[J].中国药学杂志,1998,33(10)：611
[21]杨中汉,田京城.冬凌草叶中冬凌草甲、乙素的含量测定[J].河南工业大学学报(自然科学版),2005,26(4)：53-55
[22]Yiran Jin. Yingfeng Du, Xiaowei Shi, et al. Simultaneous quantification of 19 diterpenoids in Isodon amethystoides by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry[J]. Journal of Pharmaceutical and Biomedical Analysis,2010,53:403～411
[23]Xiaotian Li, Wenjing Hou, Jingjing Song, et al. A simple and sensitive HPLC-UV method for the determination of ponicidin in rat plasma and its application in a pharmacokinetic study[J]. Biomedical Chromatography,2011,25:362～366
[24]贾欣,高岩,杜斌,等HPCE法测定冬凌草片中冬凌草甲素的含量[J].郑州大学学报(医学版),2006,41(1)：156-157
[25]Fujita E, Nagao Y, Kaneko K, et al. The anti tumor and antibacterial activity of the Isodon diterpenoids[J].Chem Pharm Bull,1976,24 (9):2118～2127
[26]Fujita E, Nagao Y, Kohno T, et al. Antitumor activity of acylated Oridonin[J]. Chem Pharm Bull,1981,29 (11):3208～3213
[27]张覃沐,陈正玉,赵清治,等.冬凌草中又一抗肿瘤有效成分[J].科学通报,1980,(22)：1051-1054
[28]Chung-Hang Leung, Susan P. Grill, Wing Lam, et al. Novel Mechanism of Inhibition of Nuclear Factor-κB DNA-Binding Activity by Diterpenoids Isolated from Isodon rubescens [J]. Molecular Pharmacology,2005,68:286-297
[29]Liu J J, Huang R W, Lin D J, et al. Ponicidin. an ent-kaurane diterpenoid derived from a constituent of the herbal supplement PC-SPES, Rabdosia rubescens, induces apoptosis by activation of caspase-3 and mitochondrial events in lung cancel-cells in Vitro [J]. Cancer Invest,2006,24 (2):136～148
[30]刘晓丹,刘文达,王春芝,等.冬凌草乙素对白血病HL-60细胞的增殖抑制作用[J].中国组织工程研究与临床康复,2010,14(27)：5062-5066
[31]刘晓丹,刘文达,王春芝,等.冬凌草乙素对白血病NB4细胞的体外诱导凋亡作用研究[J].中华肿瘤防治杂志,2010,17(12)：894-898
[32]Liu J J, Huang R W, Lin D J, et al. Antiproliferation effects of ponicidin on human myeloid leukemia cells in vitro[J]. Oncol Rep,2005,13 (4):653～657
[33]Tze-chen Hsieh, E. Kithsiri Wijeratne, Jing-yu Liang, et al. Differential control of growth, cell cycle progression, and expression of NF-κB in human breast cancer cells MCF-7, MCF-10A, and MDA-MB-231 by ponicidin and oridonin, diterpenoids from the Chinese herb Rabdosia rubescens [J]. Biochemical Biophysical Research Communications,2005, 337 (1):224-231
[34]J.-F. Zhang, P.-Q. Liu, G.-H. Chen, et al. Ponicidin inhibits cell growth on hepatocellular carcinoma cells by induction of apoptosis [J]. Digestive and Liver Disease,2007,39 (2): 160～166
[35]薛宏伟,潘祥麟.冬凌草乙素诱导GBC-SD细胞的凋亡及对Bcl-2、p53 Fas/APO-1、 C-myc表达的影响[J].中国药理学通报,2003,19(11)：1247-1251
[36]王筠,戈士文,王毅,等.几种香茶菜属二萜类化合物的抗氧化作用[J].中国药理学通报,2003,19(9)：1009-1012
[37]张覃沐,陈正玉,林晨,等.冬凌草乙素药理作用之研究[J].河南医学院学报,1979,(1)：10-14
[38]Babiker M. El-Haj, Abdelkader M. Al-Amri and Heyam S. Ali. GC-MS detection and tentative characterization of two noscapine metabolites in human urine and their potential as markers for opium and illicit heroin use [J]. Forensic Toxicology,2007,25:22～29
[39]Ioannis Papoutsis, Panagiota Nikolaou, Artemisia Dona, et al. A validated GC-MS method for the determination of A9-tetrahydrocannabinol and 11-nor-△9-tetrahydrocannabinol-9-carboxylic acid in bile samples [J]. Forensic Toxicology,2012,30:51～58
[40]Veniero Gambaro, Claudio Benvenuti, Lucia De Ferrari, et al. Validation of a GC/MS method for the determination of tramadol in human plasma after intravenous bolus [J]. Il Farmaco,2003,58:947～950
[41]S. Magiera, C. Uhlschmied, M. Rainer, et al. GC-MS method for the simultaneous determination of P-blockers, flavonoids, isoflavones and their metabolites in human urine [J]. Journal of Pharmaceutical and Biomedical Analysis,2011,56:93～102
[42]Huang Ping, Jiang Xiaofei, Zou Jiali, et al. A Novel GC-MS Bioanalytical Method for Natural Borneol and Its Application in Investigating Natural Borneol Distribution in Mice [J]. World Science and Technology,2009,11:821～827
[43]Jing Chen, Kalpana S. Paudel, Andrei V. Derbenev, et al. Simultaneous Quantification of Anandamide and Other Endocannabinoids in Dorsal Vagal Complex of Rat Brainstem by LC-MS[J].Chromatographia,2009,69:1～7
[44]Jing Zhang, Hao-Jing Song, Fan-Long Bu, et al.Determination of nifedipine concentration in human plasma by LC-MS and its application in pharmacokinetic study [J]. Journal of Chinese Pharmaceutical Sciences,2010,19:471～476
[45]Lin-lin Chen, Wei-wei Yuan, Zheng-fang Hu, et al. Determination and pharmacokinetics of DT-13 in rat plasma by LC-MS [J]. Journal of Pharmaceutical and Biomedical Analysis, 2011,56:650～654
[46]R. Nageswara Rao, Dhananjay D. Shinde, M. V. N. Kumar Talluri, et al. LC-ESI-MS determination and pharmacokinetics of adrafinil in rats[J]. Journal of Chromatography B, 2008,873:119～123
[47]Jeovanis Gil, Ania Cabrales, Osvaldo Reyes, et al.Development and validation of a bioanalytical LC-MS method for the quantification of GHRP-6 in human plasma[J]. Journal of Pharmaceutical and Biomedical Analysis,2012,60:19～25
[48]C. Webber, C. A. Stokes, S. Persiani, et al. Absorption, distribution, metabolism and excretion of the cholecystokinin-1 antagonist dexloxiglumide in the dog [J]. European Journal of Drug Metabolism and Pharmacokinetics,2004,29:15～23
[49]司倩,陈渊成,黄黎华,等LC-MS/MS法测定人血浆中奈比洛尔浓度及其在中国人体内的药代动力学[J].中国药科大学学报,2011,42(2)：136-140
[50]Michael T. Furlong, Shruti Agrawal, Dara Hawthorne, et al. A validated LC-MS/MS assay for the simultaneous determination of the anti-leukemic agent dasatinib and two pharmacologically active metabolites in human plasma:Application to a clinical pharmacokinetic study[J]. Journal of Pharmaceutical and Biomedical Analysis,2012,58: 130～135
[51]Olivier Heudi, Samuel Barteau, Franck Picard, et al. A sensitive LC-MS/MS method for quantification of a nucleoside analog in plasma:Application to in vivo rat pharmacokinetic studies [J]. Journal of Chromatography B,2009,877:1887～1893
[52]Rodolpho C. Braga, Andrea C. B. Torres, Camille B. Persiano, et al. Determination of the cardioactive prototype LASSBio-294 and its metabolites in dog plasma by LC-MS/MS: Application for a pharmacokinetic study [J]. Journal of Pharmaceutical and Biomedical Analysis,2011,55:1024～1030
[53]Isam I. Salem, Musab Alkhatib, Naji Najib. LC-MS/MS determination of betamethasone and its phosphate and acetate esters in human plasma after sample stabilization [J]. Journal of Pharmaceutical and Biomedical Analysis,2011,56:983～991
[54]Raymond Naxing Xu, Leimin Fan, Matthew J. Rieser, et al. Recent advances in high-throughput quantitative bioanalysis by LC-MS/MS [J]. Journal of Pharmaceutical and Biomedical Analysis,2007,44:342～355
[55]Alfonso Espada, Manuel Molina-Martin, Jeffrey Dage, et al. Application of LC/MS and related techniques to high-throughput drug discovery [J]. Drug Discovery Today,2008,13: 417-423
[56]Ian D. Wilson, J.K. Nicholson. Solid phase extraction chromatography and NMR spectroscopy (SPEC-NMR) for the rapid identification of drug metabolites in urine [J]. Journal of Pharmaceutical and Biomedical Analysis,1988,6:151～165
[57]Farida Y. K. Ghauri, Andre E. M. McLean, Denis Beales, et al. Induction of 5-oxoprolinuria in the rat following chronic feeding with N-acetyl 4-aminophenol (paracetamol)[J]. Biochemical Pharmacology,1993,46:953～957
[58]Klaus Albert, Ernst Bayer. High-performance liquid chromatography-nuclear magnetic resonance on-line coupling [J]. TrAC Trends in Analytical Chemistry,1988,7:288～293
[59]John C Lindon, Jeremy K Nicholson, Ian D Wilson. Directly coupled HPLC-NMR and HPLC-NMR-MS in pharmaceutical research and development [J]. Journal of Chromatography B:Biomedical Sciences and Applications,2000,748:233～258
[60]Vlassios Goulas, Ana Maria Gomez-Caravaca, Vassiliki Exarchou, et al. Exploring the antioxidant potential of Teucrium polium extracts by HPLC-SPE-NMR and on-line radical-scavenging activity detection [J]. LWT-Food Science and Technology,2012,46: 104～109
[61]辛普森C F.实用高效液相色谱法.徐征帆译.北京：中国建筑出版社,1981,2
[62]Lukas Kaminski, Matthias Degenhardt. Joachim Ermer, et al. Efficient and economic HPLC performance qualification [J]. Journal of Pharmaceutical and Biomedical Analysis,2010, 51:557-564
[63]Kallol M. Biswas, Bryan C. Castle, Bernard A. Olsen, et al. A simple and efficient approach to reversed-phase HPLC method screening [J]. Journal of Pharmaceutical and Biomedical Analysis,2009,49:692～701
[64]杜斌,张振中.现代色谱技术[M].郑州：郑州大学出版社,2002,124
[65]Xia J H. Validation of bio-analytical methods for Pharmacokinetics, bioavailability and Bioequivalence studies [J]. Asian J Drug Metab Pharmacokinet,2001,1 (20):95～100
[66]Jian Ge, Wang You-Wei, Lu Xiao-Cong, et al. Determination of oridonin in rat plasma by reverse phase high-performance liquid chromatography [J]. Journal of Pharmaceutical and Biomedical Analysis,2007,43:793～797
[67]Yinghao Mei, Jie Xu, Jihui Zhao, et al. An HPLC method for determination of oridonin in rabbits using isopsoralen as an internal standard and its application to pharmacokinetic studies for oridonin-loaded nanoparticles [J]. Journal of Chromatography B,2008,869: 138～141
[68]Lei Gao, Dianrui Zhang, Minghui Chen, et al. Studies on pharmacokinetics and tissue distribution of oridonin nanosuspensions [J]. International Journal of Pharmaceutics,2008, 355:321～327
[69]刘德文,张毅,李德凤,等.8-乙酰哈巴苷大鼠体内药代动力学[J].中国实验方剂学杂志,2011,17(20)：129-132
[70]黄敏文,王广基,孙建国,等RP-HPLC法测定Beagle犬血浆中烟酸浓度及烟酸药代动力学研究[J].中国临床药理学与治疗学,2005,10(3)：302-305
[71]Ioannis Niopas, Athanasios C. Daftsios. A validated high-performance liquid chromatographic method for the determination of glibenclamide in human plasma and its application to pharmacokinetic studies [J]. Journal of Pharmaceutical and Biomedical Analysis,2002,28:653～657
[72]刘振胜,赵艳,闫美兴,等HPLC法测定盐酸氟桂利嗪分散片的血药浓度及药动学研究[J].中国新药杂志,2005,14(8)：1041-1044
[73]Vinod P. Shah, Kamal K. Midha, John W. A. Findlay, et al. Bioanalytical Method Validation-A Revisit with a Decade of Progress [J]. Pharmaceutical Research,2000,17: 1551～1557
[74]张剑萍,郭澄.生物样品分析中的方法学验证[J].中国药房,2008,19(31)：2469-2471
[75]李好枝主编.体内药物分析[M].北京：人民卫生出版社2008,58
[76]Maria Toth, Andrea Bereczki, Sandor Drabant, et al. Gas chromatography nitrogen phosphorous detection (GC-NPD) assay of tofisopam in human plasma for pharmacokinetic evaluation [J]. Journal of Pharmaceutical and Biomedical Analysis,2006,41:1354～1359
[77]Vikneswaran Murugaiyah, Kit Lam Chan. Analysis of lignans from Phyllanthus niruri L. in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic study [J]. Journal of Chromatography B,2007,852:138～144
[78]Fawzy Elbarbry, Ahmed Attia, Ahmed Shoker. Validation of a new HPLC method for determination of midazolam and its metabolites:Application to determine its pharmacokinetics in human and measure hepatic CYP3A activity in rabbits [J]. Journal of Pharmaceutical and Biomedical Analysis,2009,50:987-993
[79]Sicen Wang, Qinhua Chen, Langchong He. Development and validation of a gas chromatography-mass spectrometry method for the determination of isoimperatorin in rat plasma and tissue:Application to the pharmacokinetic and tissue distribution study[J]. Journal of Chromatography B,2007,852:473-478
[80]Shaoying Hou, Fang Wang, Yingmei Li. Pharmacokinetic study of mangiferin in human plasma after oral administration [J]. Food Chemistry,2009,50:987～993
[81]孙毓庆主编.现代色谱法及其在药物分析中的应用.第一版.北京：科学出版社,2005：72
[82]王敏智,王兴,王萍.色谱技术在中药药动学研究中的应用进展[J].时珍国医国药,2010,21(11)：2971-2973
[83]李海生,白海娇.高效液相色谱应用中的若干问题与解决方法[J].天津药学,2006,18(2)：5-7
[84]刘昌孝主编.实用药物动力学.第一版.北京：中国医药科技出版社,2003：335
[85]闻俊.生物样品高通量液相色谱分析方法学研究及其药代动力学应用[D].[博士学位论文].上海：第二军医大学,2008
[86]张君仁,臧恒昌主编.体内药物分析.第一版.北京：化学工业出版社,2003：43
[87]李发美主编.医药高效液相色谱技术.北京：人民卫生出版社,1999：56
[88]宁宇,赵培荣,连小珂,等.反相高效液相色谱法测定人体血浆中冬凌草甲素含量[J].肿瘤基础与临床,2006,19(3)：180-182
[89]张典瑞,任天池,娄红祥,等.冬凌草甲素固态类脂纳米粒在小鼠体内的组织分布及兔体内的药代动力学[J].药学学报,2005,40(6)：573-576
[90]Yingfeng Du, Pengwei Liu, Xiaowei Shi, et al. A novel analysis method for diterpenoids in rat plasma by liquid chromatography-electrospray ionization mass spectrometry [J]. Analytical Biochemistry,2010,407:111～119
[91]杨桂芹,房世红,董欣,等LC-MS法测定犬血浆中冬凌草甲素含量[J].药物分析杂志,2011,31(5)：912-916
[92]顾轶,王广基,孙建国HPLC-MS测定Beagle犬血浆中非洛地平的浓度[J].华西药学杂志,2006,21(4)：372-374
[93]王萍,陈醒言,邱相君,等.高效液相色谱法测定健康人血浆中舍曲林浓度[J].中国临床药理学杂志,2006,22(99)：69-72
[94]邓泮,段小涛,陈笑艳,等.液相色谱-串联质谱法测定犬血浆中布地奈德[J].药学学报,2008,43(1)：76-80
[95]吴民淑,王广基,蔡晓辉,等.液相色谱-质谱联用法测定犬血浆中盐酸关附甲素的血药浓度及其药代动力学[J].药学学报,2002,37(7)：551-554
[96]何秀琼,裴利霞,王一涛,等.高效液相色谱法研究大鼠灌胃黄芩素的药动学[J].中国医院药学杂志,2010,30(22)：1901-1905
[97]吕晶,黄熙,段重高,等.胡黄连苷-Ⅰ在大鼠和犬体内药动学研究[J].解放军药学学报,2005,21(1)：1-3
[98]毛惠英,张丹,李鑫楠,等RP-HPLC测定家兔血浆中的儿茶素和表儿茶素[J].华西药学杂志,2009,24(1)：66-67
[99]汤南,张丹,孙文霞,等.丹参酮ⅡA磺酸钠在家兔体内的药代动力学研究药物分析杂志,2009,29(5)：760-763
[100]张凤霞, 贾振华,戴伟东,等.中药通心络对抑郁-动脉粥样硬化大鼠干预作用的血浆代谢组学研究[J].中国科学,2010,40(6)：725-732
[101]戴伟东,张凤霞,贾振华,等.基于液相色谱-质谱联用技术的代谢组学方法用于中药通心络和人参对过度疲劳大鼠干预作用的评价[J].色谱2011,29(11)：1049-1054
[102]樊惠远,赵清治,王汉清,等.冬凌草乙素的化学研究[J].河南医学院学报,1979,(1)：14-16
[103]寇娴,张雁冰,王桂红,等.冬凌草乙素-p-环糊精包合物的研究[J].郑州大学学报(自然科学版),1998,30(30)：64-66
[104]FDA. Guidance for Indust-Bioanalytical Method Validation [Z].2001 http //www/fda.gov/cder/guidance/index.htm.
[105]国家食品药品监督管理局药品审评中心.化学药物非临床药代动力学研究技术指导原则[M].2005.
[1]Xu Zhu, YaXin Sun, XiaoJing He, et al. HPLC-UV method with solidphase extraction for the quantitative determination of biapenem in human plasma and its application in pharmacokinetic study[J]. Journal of Chinese Pharmaceutical Sciences 2011,20:70～76
[2]Ding Jinsong, Zhang Bikui, Li Huande, Liu Yizhao and Deng Hang. HPLC Determination of Captopril in Human Plasma with Pre-column Derivation and Solid-phase Extraction and Studies on Its Pharmacokinetic and Relative Bioavailability [J]. Journal of Chinese Pharmaceutical Sciences 2001,10 (3):152～156
[3]李珍,唐世新,张晋萍,等.固相萃取-高效液相色谱法测定人血浆中吡格列酮浓度[J].中国医院药学杂志,2003,23(11)：653-655
[4]李智平,钟明康,施孝金,等.固相萃取-高效液相色谱法测定人血浆中硝苯地平浓度[J].中国临床药学杂志,2005,14(2)：115-117
[5]陈昆,王静,王睿,等.固相萃取HPLC检测生物样品中的甲苯磺丁脲和代谢产物及其人体药代动力学研究[J].药物分析杂志,2005,25(3)：50
[6]张颖.生物样品预处理技术及应用进展[J].天津药学,2006,18(1)：57
[7]Jeff Wise, Terry Danielson, Ashraf Mozayani, et al. Analysis of amphetamine, methamphetamine, methylenedioxyamphetamine and methylenedioxymethamphetamine in whole blood using in-matrix ethyl chloroformate derivatization and automated headspace solid-phase microextraction followed by GC-MS[J]. Forensic Toxicol,2008 (26):66～ 70
[8]Satt erfield M, Black D M, Brodbelt J S. Detect ion of the isoflavone aglycones genist ein and daidzein inurine using sol id-phase microextract ion high performance liquid chromatography-electrospray ionizat ion mass spectrometry[J]. J Chromatogr B Biomed Sci Appl,2001,759 (1):33
[9]Marcin Wasowicz, Angela Jerath, Barbara Bojko, et al. Use of a novel technique, solid phase microextraction, to measure tranexamic acid in patients undergoing cardiac surgery [J]. Canadian Journal of Anesthesia,2012, (59):14～20
[10]Klime J, Sochor J, Kriz J. A study of the conditions of the supercritical fluid extraction in the analysis of selected ant i-inflammatory drugs in plasma [J]. Faracp,2002,57 (2): 117
[11]Allen D L, Scott K S, Oliver J S. Comparison of solidphase ex tractio n and supercritical fluid extraction for the analy sis of mor phine in w hole blood[J]. J Anal Tox ical,1999, 23 (3):216～221
[12]Long-Hu Wang, Yan-Hong Mei, Feng Wang, et al. A novel and efficient method combining SFE and liquid-liquid extraction for separation of coumarins from Angelica dahurica[J]. Separation and Purification Technology,2011,77:397～401
[13]Xue Y J, Liu J, Unger S. A 96-well single-pot liquid-liquid extraction, hydrophilic interaction liquid chromatography-mass spectrometry method for the determination of muraglitazar in human plasma [J]. J Pharm Biomed Anal,2006,41 (3):979～988
[14]Wen Zhang, Xuni Cao, Yunfeng Xie, et al. Simultaneous determination of the monoamine neurotransmitters and glucose in rat brain by microdialysissampling coupled with liquid chromatography-dual electrochemical detector [J]. Journal of Chromatography B,2003, 785:327-336
[15]Anita L Freed, Josh D Cooper, Malonne Ⅰ Davies, et al. Investigation of the metabolism of substance P in rat striatum by microdialysissampling and capillary electrophoresis with laser-induced fluorescence detection [J]. Journal of Microbiological Methods,2003,109: 23～29
[16]Gang Cao, Hao Cai, Yun Zhang, et al. Identification of metabolites of crude and processed Fructus Corni in rats by microdialysissampling coupled with electrospray ionization linear quadrupole ion trap mass spectrometry [J]. Journal of Pharmaceutical and Biomedical Analysis,2011,56:118～125
[17]Xiaoping Ao, Robert F. Rotundo, Daniel J. Loegering, et al. In vivo microdialysissampling of cytokines produced in mice given bacterial lipopolysaccharide[J]. Journal of Microbiological Methods,2005,62:327～336