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

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2015-09, Vol.1001, p.22-26
• Main Authors: Ding, Li-kun, Yang, Lin, Chen, Su-ning, Li, Jian-Kang, Wen, Ai-dong
• Format: Article
• Language: English
• Subjects: Active metabolite; Adolescent; Adult; Antineoplastic Agents - blood; Antineoplastic Agents - pharmacokinetics; Area Under Curve; Chromatography, Liquid - methods; Half-Life; Healthy Volunteers; Humans; Indoles - blood; Indoles - pharmacokinetics; LC–MS/MS; Limit of Detection; Pharmacokinetics; Pyrroles - blood; Pyrroles - pharmacokinetics; Reproducibility of Results; Subutinib; Tandem Mass Spectrometry - methods; Young Adult
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2015.07.015

•LC–MS/MS method was developed for determination of subutinib in human plasma.•It is successfully applied to pharmacokinetic study of subutinib.•This is first time to report the pharmacokinetic of subutinib maleate capsules. 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 C18 (150mm×2.1mm, 3.5μm), with methanol–0.2% formic acid solution (73:27, v/v) as mobile phase at flow rate of 0.2ml/min. The linear range was 0.25–100ng/mL for subutinib and 0.125–50.0ng/mL for its active metabolite, with lower limit of quantitation of 0.25ng/mL and 0.125ng/mL, respectively. Intra- and inter-run precision were within 7.0 and 13.1%, and the accuracies (relative errors) were