Simultaneous determination of subutinib and its active metabolite in human plasma by LC-MS/MS: Application to pharmacokinetic study

被引:1
作者
Ding Li-kun [1 ]
Yang Lin [1 ]
Chen Su-ning [1 ]
Li Jian-kang [1 ]
Wen Ai-dong [1 ]
机构
[1] Fourth Mil Med Univ, Xijing Hosp, Dept Pharm, Xian 710032, Shaanxi, Peoples R China
来源
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2015年 / 1001卷
关键词
Subutinib; Active metabolite; LC-MS/MS; Pharmacokinetics;
D O I
10.1016/j.jchromb.2015.07.015
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A selective liquid chromatographic-mass spectrometric method (LC-MS/MS) has been established and validated for simultaneous determination of subutinib and its active metabolite in human plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Wondasil C-18 (150 mm x 2.1 mm, 3.5 mu m), with methanol-0.2% formic acid solution (73:27, v/v) as mobile phase at flow rate of 0.2 ml/min. The linear range was 0.25-100 ng/mL for subutinib and 0.125-50.0 ng/mL for its active metabolite, with lower limit of quantitation of 0.25 ng/mL and 0.125 ng/mL, respectively. Intra- and inter-run precision were within 7.0 and 13.1%, and the accuracies (relative errors) were <7.0 and 8.0%, with the extraction recoveries 97.0-101.2% and 93.0-98.1% for the two analytes, respectively. The validated method was successfully applied to a pharmacokinetic study of subutinib and its active metabolite in human after oral administration of subutinib maleate capsules. (C) 2015 Published by Elsevier B.V.
引用
收藏
页码:22 / 26
页数:5
相关论文
共 5 条
[1]  
Chen X., 2014, BIOMED CHROMATOGR
[2]  
Chinese State Food and Drug Administration, 2005, GUID BIOAV BIOEQ STU
[3]  
EMEA/CPMP, 2001, CPMPEWP140198 EUR AG
[4]  
[FDA CDER], 2003, GUID IND BIOAV BIOEQ
[5]  
FDA CDER, 2018, GUID IND BIOAN METH