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上海药物代谢研究中心
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钟大放研究组
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钟大放研究组
钟大放研究组

    

  课题组工作人员11名,其中研究员1名,副研究员1名,助理研究员5名,博士后2名,博士生4名,硕士生2名,联合培养硕士生6名。

    

    

  药物代谢反应机理和代谢产物结构鉴定;反应性代谢物筛查;药物代谢的遗传多态性;药物代谢酶和药物转运体的抑制和诱导及其临床意义;药动学生物样品分析方法学;创新药物临床前和临床ADME试验。

  

 

   

  近5年来,发表期刊论文98篇,其中SCI论文57篇。开展了20余种创新药物的临床前及临床ADME研究。阐明了艾瑞昔布、埃克替尼、氟马替尼、20(S)-原人参二醇、阿比朵尔、拉呋替丁、胺碘酮等药物的体内代谢途径。采用LC-MS/MS分析技术建立了200余种药物的血浆样品定量分析方法,包括对药物和代谢产物的同时分析,肽类药物和寡核苷酸药物的血浆样品分析,经柱前衍生化后进行分析等。发现了CYP2C9, 2C19等基因多态性对氯诺昔康、格列齐特、格列吡嗪等药物临床药动学的显著影响。采用微生物代谢转化、肝微粒体代谢转化等方法制备代谢物对照品并研究了多种药物的代谢物种差异。采用放射性同位素标记法研究了多种新药的体内代谢过程。

   

 
  1. Liu J, Chen XY, Liu K, Li L, Zhong DF*. Derivatization of (5R)-hydroxytriptolide with benzylamine to enhance mass spectrometric detection: Application to a Phase I pharmacokinetic studie. Analytica Chimica Acta, 2011, 689: 69-76
  2. Li L, Chen XY, Li D, Zhong DF*. Identification of 20(S)-protopanaxadiol metabolites in human liver microsomes and human hepatocytes. Drug Metabolism and Disposition, 2011, 39: 472-483
  3. Deng P, You TG, Chen XY, Yuan T, Huang HH, Zhong DF*. Identification of amiodarone metabolites in human bile by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. Drug Metabolism and Disposition, 2011, 39: 1058-1069
  4. Gao CY, Chen XY, Zhong DF*. Absorption and disposition of scutellarin in rats: a pharmacokinetic explanation for the high exposure of its isomeric metabolite. Drug Metabolism and Disposition, 2011, 39: 2034-2044
  5. Zhong DF. Bioanalysis in China. Bioanalysis, 2010, 2: 153-156
  6. Gong Aishen, Chen XY, Deng P, Zhong DF*. Metabolism of flumatinib, a novel antineoplastic tyrosine kinase inhibitor, in chronic myelogenous leukemia patients. Drug Metabolism and Disposition, 2010, 38: 1328-1340
  7. Tan B, Zhang YF, Chen XY, Zhao XH, Li GX, Zhong DF*. The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects. European Journal of Clinical Pharmacology, 2010, 66: 145-151
  8. Liu J, Chen XY, Hu YH, Cheng G, Zhong DF*. Quantification of the major metabolites of bromhexine in human plasma using RRLC-MS/MS and its application to pharmacokinetics.Journal of Pharmaceutical and Biochemical Analysis, 2010, 51: 1134-1141
  9. Deng P, Chen XY, Zhang GD, Zhong DF*. Bioanalysis of an oligonucleotide and its metabolites by liquid chromatography-tandem mass spectrometry. Journal of Pharmaceutical and Biochemical Analysis, 2010, 52: 571-579
  10. Deng P, Chen XY, Zhong DF*. Quantification of polar drugs in human plasma with LC-MS/MS. Bioanalysis, 2009, 1: 187-203
  11. Liu J, Duan XT, Chen XY, Zhong DF*. Determination of eptifibatide concentration in human plasma utilizing the liquid chromatography–tandem mass spectrometry method. Journal of Chromatography B, 2009, 877: 527-532
  12. Zhan Y, Chen XY, Zhao XH, Zhong DF*. Rapid and sensitive liquid chromatography-tandem mass spectrometry method for the determination of leuprolide in human serum. Journal of Chromatography B, 2009, 877: 3194-3200
  13. Meng J, Zhao LZ, Hu YH, Chen XY, Zhong DF*. Synthesis of [3-3H]20(S)-protopanaxadiol. Journal of Labelled Compounds and Radiopharmaceuticals, 2009, 52: 482-484
  14. Wang YY, Chen XY, Li Q, Zhong DF*. Metabolite identification of arbidol in human urine by the study of CID fragmentation pathways using HPLC coupled with ion trap mass spectrometry. Journal of Mass Spectrometry, 2008, 43: 1099-1109
  15. Wang YY, Chen XY, Li Q, Zhong DF*. Characterization of metabolites of a novel histamine H2-receptor antagonist, lafutidine, in human liver microsomes by liquid chromatography coupled with ion trap mass spectrometry. Rapid Communications in Mass Spectrometry, 2008, 22: 1843-1852
  16. Guan ZM, Chen XY, Wang YX, Zhong DF*. Metabolite identification of a new antitumor agent icotinib in rats using liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry, 2008, 22: 2176-2184
  17. Zhang YF, Si DY, Chen XY, Lin N, Guo YJ, Zhou H, Zhong DF*. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects. British Journal of Clinical Pharmacology, 2007, 64: 67-74
  18. Li XY, Chen XY, Zhong DF*. Validated method for rapid inhibition screening of six cytochrome P450 enzymes by liquid chromatography-tandem mass spectrometry. Journal of Chromatography B, 2007, 852:  128-137
  19. Duan XT, Chen XY, Yang YM, Zhong DF*. Precolumn derivatization of cysteine residues for quantitative analysis of five major cytochrome P450 isoenzymes by liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry, 2007, 21: 3234-3244
  20. Huang HH, Yang XW, Li Qiang, Sun L, Zhong DF*. Biotransformation of tolbutamide to 4’-tolbutamide by the fungus Cunninghamella blakesleeana. Applied Microbiology and Biotechnology, 2006, 72: 486-491.

  

  LC-MS/MS仪器3台,UPLC-Q/TOF MS仪器1台,细胞生物学实验室开展药物代谢酶、转运体、Caco-2细胞通透性实验和微生物代谢转化实验相关设备。

   

 

 
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