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学科主题: 药学
题名:
Analysis of cyclosporine A and its metabolites in rat urine and feces by liquid chromatography-tandem mass spectrometry
作者: 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
发表日期: 2010-05-01
DOI: 10.1016/j.jchromb.2010.03.032
卷: 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
所属项目编号: 2006BA109800 ; 07C26223201333 ; JHB05-46 ; H200630
项目资助者: 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
WOS记录号: WOS:000277672000017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57543
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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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

Recommended Citation:
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.
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