title: Simultaneous determination of subutinib and its active metabolite in human plasma by LC-MS/MS: Application to pharmacokinetic study.
abstract: 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<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.
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi 710032, China.
authors.forename: Li-kun
authors.initials: LK
authors.lastname: Ding
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi 710032, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi 710032, China.
authors.forename: Su-ning
authors.initials: SN
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi 710032, China.
authors.forename: Jian-kang
authors.initials: JK
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi 710032, China. Electronic address: adwen-2004@hotmail.com.
authors.forename: Ai-dong
authors.initials: AD
authors.lastname: Wen
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D057230:Limit of Detection; D011758:Pyrroles / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C000607733:subutinib
keywords: Active metabolite; LC–MS/MS; Pharmacokinetics; Subutinib