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Analysis of cyclosporine A and its metabolites in rat urine and feces by liquid chromatography-tandem mass spectrometry
Fang, Zhi-gang1; You, Ben-gang1; Chen, Ya-gen1; Zhang, Jian-kang1; Liu, Yue-qing1; Zhang, Xue-nong1; Zhang, Qiang2
关键词Cyclosporine a Metabolites Lc Ms/ms
刊名JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
2010-05-01
DOI10.1016/j.jchromb.2010.03.032
878期:15-16页:1153-1162
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemical Research Methods ; Chemistry, Analytical
研究领域[WOS]Biochemistry & Molecular Biology ; Chemistry
关键词[WOS]PH-SENSITIVE NANOPARTICLES ; T-CELL PROLIFERATION ; WHOLE-BLOOD ; TRANSPLANT PATIENTS ; CONCANAVALIN-A ; QUANTIFICATION ; LYMPHOCYTES ; ASSAY
英文摘要

A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of cyclosporine A (CyA) and the identification of its metabolites in rat urine and feces. The analytes were extracted from waste samples via liquid-liquid extraction. A Turboionspray source was used as a detector. It was operated in a positive ion mode with transitions of m/z 1225 m/z 1112 for CyA and in a selected multiple reactions monitoring (MRM) mode with transitions of m/z 1239 m/z 1099 for the internal standard (cyclosporine D, CyD). Linear calibration curves were obtained for CyA concentration ranges of 12.5-250 ng mL(-1) in urine and 2.5-375 ng mg(-1) in feces. The intra- and inter-day precision values (relative standard deviation) obtained were less than 8%, and the accuracy was within +/-15% for each of the analytes. Extraction recoveries of CyA and CyD were both over 80%. The identification of the metabolites and elucidation of their structure were performed on the basis of their retention times and mass spectrometry fragmentation behaviors. A total of seven metabolites in rat feces were identified as dimethyl CyA, hydroxy CyA, and dihydroxy CyA after the oral administration of cyclosporine A-Eudragit (R) S100 nanoparticles (CyA-NP). Six of these metabolites were also detected in rat urine. A possible metabolic pathway was also proposed. The newly developed method was proven to be sensitive, simple, reproducible, and suitable for the rapid determination of CyA. It was successfully employed to study the excretion of CyA in rats and could be used to better understand the in vivo metabolism of CyA-NP, a potentially effective nanoparticle system. (C) 2010 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000277672000017
项目编号2006BA109800 ; 07C26223201333 ; JHB05-46 ; H200630
资助机构National Key Technology R&amp ; D Program of the 11th Five-year Plan of China ; National Science and Technology Ministry ; Department of Education of Jiangsu Province ; Health Department of Jiangsu Province
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57543
专题北京大学药学院_药剂学系
作者单位1.Soochow Univ, Coll Pharm, Suzhou 215123, Jiang Su Prov, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100083, Peoples R China
推荐引用方式
GB/T 7714
Fang, Zhi-gang,You, Ben-gang,Chen, Ya-gen,et al. Analysis of cyclosporine A and its metabolites in rat urine and feces by liquid chromatography-tandem mass spectrometry[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2010,878(15-16):1153-1162.
APA Fang, Zhi-gang.,You, Ben-gang.,Chen, Ya-gen.,Zhang, Jian-kang.,Liu, Yue-qing.,...&Zhang, Qiang.(2010).Analysis of cyclosporine A and its metabolites in rat urine and feces by liquid chromatography-tandem mass spectrometry.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,878(15-16),1153-1162.
MLA Fang, Zhi-gang,et al."Analysis of cyclosporine A and its metabolites in rat urine and feces by liquid chromatography-tandem mass spectrometry".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 878.15-16(2010):1153-1162.
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