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《Chinese Journal of New Drugs and Clinical Remedies》 2012-07
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Simultaneous determination of vorinostat and its metabolite 4-anilino-4-oxobutanoic acid in human serum and urine by liquid chromatography-tandem mass spectrometry

DU Xiao-lang~1,ZHU He~1,DING Li~1,MA Peng-cheng~2,WANG Xun-qiang~3,LI Wen-bo~1,LUO Xue-mei~1,WANG Jing~1 (1.Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing JIANGSU 210009, China;2.Dermatology Hospital Affiliated to Chinese Academy of Medical Sciences,Nanjing JIANGSU 210042, China;3.Chia-Tai Tianqing Pharmaceutical Co.Ltd,Nanjing JIANGSU 210038,China)  
AIM To establish a LC-MS/MS method for the simultaneous determination of vorinostat and its metabolite 4-anilino-4-oxobutanoic acid(M2) in human serum and urine.METHODS Serum samples were deproteinized using 3:1 methanol/serum,and analyzed by HPLC on a Amethyst C_(18)-P column(150 mm×2.1 mm,5μm) with a mobile phase of methanol-5 mmol·L~(-1) ammonium acetate buffer solution containing 2% formic acid(45:55,V/V).Urine samples were diluted and analyzed by HPLC on a Hedera ODS-2 C_(18) column (150 mm×2.1 mm,5μm) with a mobile phase of methanol-30 mmol·L~(-1) ammonium acetate buffer solution containing 2%formic acid(45:55,V/V).An electrospray ionization source was applied and performed in positive ion mode.The ion transitions recorded in multiple reaction monitoring mode were m/z 265.2→232.2 for vorinostat,m/z 194.1→176.1 for M2 and m/z 180.1→110.1 for the internal standard(IS),respectively. RESULTS The calibration curves were linear over the range of 2.004 - 1 503μg·L~(-1) for vorinostat and 5.015 - 5 015μg·L~(-1) for M2,respectively,in serum.The average recoveries of vorinostat and M2 in serum were more than 98.3%and 96.8%,respectively.The calibration curves were linear over the range of 0.030 06 - 20.04 mg·L~(-1) for vorinostat and 1.003-300.9 mg·L~(-1) for M2,respectively,in urine.The average recoveries of vorinostat and M2 in urine were more than 96.8%and 96.5%,respectively.The interference due to decomposition of vorinostat glucuronide in the ionization source of the mass spectrometer was avoided by carrying out the chromatographic separation.CONCLUSION The developed methods can be applied to the pharmacokinetic study and therapeutic drug monitoring of vorinostat and its metabolite.
【CateGory Index】: R969.1
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【Citations】
Chinese Journal Full-text Database 2 Hits
1 JIANG Shao-hong MA Xu-dong Zhangzhou Affiliated Hospital of Fujian Medical University,Zhangzhou FUJIAN 363000,China XU Yun-lu School of Pharmacy,Fujian Medical University,Fuzhou FUJIAN 350004,China;Update of histone deacetylase inhibitors[J];Chinese Journal of New Drugs and Clinical Remedies;2008-08
2 YU Yong1,SUN Lu-ning1,DU Xiao-lang1,RAO Ya-kun1, DING Wen1,DING Li1,XIAO Hui-feng2,CHEN Yi-zhi3 (1.Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009,China;2.Guangzhou Boji New Drug Clinical Research Center Co.,Ltd.,Guangzhou 510000,China;3.Hainan Huanglong Pharmaceutical Co.,Ltd.,Haikou 571127,China);Determination of p-Acetaminobenzoic Acid and N,N-Dimethylamino-2-propanol in Human Urine by LC-MS and Study on Their Urinary Excretion Profiles[J];Progress in Pharmaceutical Sciences;2011-09
【Co-citations】
Chinese Journal Full-text Database 2 Hits
1 WANG Feng-qin,CHEN Xue-juan,ZHANG Xiang-ning.Department of Obstetrics and Gynecology,Qilu Hospital,Shandong University, Ji’nan 250014, China;VPA increase the Sensitivity of Human Ovarian Cancer Cell Line COC1/DDP to Cisplatin in Vitro[J];Medicine & Philosophy(Clinical Decision Making Forum Edition);2010-04
2 LIU Rui-juan1,ZHU He1,DING Li 1,SHAKYA Shailendra1,YANG Zhong-lin2,CHENG Lu1(1.Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009,China; 2.College of Traditional Chinese Medicine,China Pharmaceutical University,Nanjing 210009,China);Study on pharmacokinetics of asperosaponin Ⅵ and its active metabolite in rats[J];China Journal of Chinese Materia Medica;2013-14
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Chinese Journal Full-text Database 3 Hits
1 YANG Jing,DING Li & LIU WenYing Key Laboratory of Drug Quality Control and Pharmacovigilance,Ministry of Education;Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009,China;LC-MS in biomedical analysis:Common issues and counterplan[J];Scientia Sinica(Chimica);2010-06
2 Xie Ai-Hua Li Bo-Yu Liao Chen-Zhong Li Zhi-Bin Lu Xian-Ping Shi Le-Ming Zhou Jia-Ju (Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080; Chipscreen Biosciences, Limited, Shenzhen 518057);Docking Study of HDAC Implication for Benzamide Inhibitors Binding Mode[J];Acta Physico-chimica Sinica;2004-06
3 DAI Qing,LIU Song-qing,XIA Pei-yuan,CHEN Yong-chuan,TANG Min,XIANG Rong-feng(Department of Pharmacy,Southwest Hospital,Third Military Medicine University,Base of Clinical Trial,Chongqing 400038,China);Determination of mizoribine in human plasma by high performance liquid chromatography and its pharmacokinetics study[J];Chinese Journal of Hospital Pharmacy;2009-20
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