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Simultaneous determination of capecitabine and its three nucleoside metabolites in human plasma by high performance liquid chromatography-tandem mass spectrometry

文献类型：期刊论文

作者Deng, Pan2; Ji, Cheng1,2; Dai, Xiaojian2; Zhong, Dafang2; Ding, Li1; Chen, Xiaoyan2
刊名JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
出版日期2015-05-01
卷号989页码:71-79
关键词Capecitabine 5-Fluorouracil Nucleoside metabolites LC-MS/MS
ISSN号1570-0232
DOI10.1016/j.jchromb.2015.03.002
文献子类Article
英文摘要Capecitabine (Cape) is a prodrug that is metabolized into 5'-deoxy-5-fluorocytidine (DFCR), 5'-deoxy-5-fluorouridine (DFUR), and 5-fluorouracil (5-FU) after oral administration. A liquid chromatography-tandem mass spectrometry method for the simultaneous determination of capecitabine and its three metabolites in human plasma was developed and validated. The ex vivo conversion of DFCR to DFUR in human blood was investigated and an appropriate blood sample handling condition was recommended. Capecitabine and its metabolites were extracted from 100 mu L of plasma by protein precipitation. Adequate chromatographic retention and efficient separation were achieved on an Atlantis dC(18) column under gradient elution. Interferences from endogenous matrix and the naturally occurring heavy isotopic species were avoided. Detection was performed in electrospray ionization mode using a polarity-switching strategy. The method was linear in the range of 10.0-5000 ng/mL for Cape, DFCR, and DFUR, and 2.00-200 ng/mL for 5-FU. The LLOQ was established at 10.0 ng/mL for Cape, DFCR, and DFUR, and 2.00 ng/mL for 5-FU. The inter- and intra-day precisions were less than 13.5%, 11.1%, 9.7%, and 11.4%, and the accuracy was in the range of -13.2% to 1.6%, -2.4% to 2.5%, -7.1% to 8.2%, and -2.0% to 3.8% for Cape, DFCR, DFUR, and 5-FU, respectively. The matrix effect was negligible under the current conditions. The mean extraction recoveries were within 105-115%, 92.6-101%, 94.0-100%, and 85.1-99.9% for Cape, DFCR, DFUR, and 5-FU, respectively. Stability testing showed that the four analytes remained stable under all relevant analytical conditions. This method has been applied to a clinical bioequivalence study. (C) 2015 Elsevier B.V. All rights reserved.
WOS关键词ANTICANCER AGENT CAPECITABINE ; CANCER-PATIENTS ; MS/MS METHOD ; PHARMACOKINETICS ; 5'-DEOXY-5-FLUOROCYTIDINE ; 5-FLUOROURACIL ; HPLC
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000353081400009
出版者ELSEVIER SCIENCE BV
源URL[http://119.78.100.183/handle/2S10ELR8/276560]  
专题上海药物代谢研究中心
通讯作者Chen, Xiaoyan
作者单位1.China Pharmaceut Univ, Dept Pharmaceut Anal, Nanjing 210009, Jiangsu, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Deng, Pan,Ji, Cheng,Dai, Xiaojian,et al. Simultaneous determination of capecitabine and its three nucleoside metabolites in human plasma by high performance liquid chromatography-tandem mass spectrometry[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2015,989:71-79.
APA Deng, Pan,Ji, Cheng,Dai, Xiaojian,Zhong, Dafang,Ding, Li,&Chen, Xiaoyan.(2015).Simultaneous determination of capecitabine and its three nucleoside metabolites in human plasma by high performance liquid chromatography-tandem mass spectrometry.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,989,71-79.
MLA Deng, Pan,et al."Simultaneous determination of capecitabine and its three nucleoside metabolites in human plasma by high performance liquid chromatography-tandem mass spectrometry".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 989(2015):71-79.

入库方式： OAI收割

来源：上海药物研究所

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