Determination of sunitinib and its active metabolite, N‐desethyl sunitinib in mouse plasma and tissues by UPLC‐MS/MS: assay development and application to pharmacokinetic and tissue distribution studies. (8th October 2014)

• Record Type: Journal Article
• Authors: Chen, Xiao; Wang, Zhong; Liu, Mengping; Liao, Min; Wang, Xinfeng; Du, Huajuan; Chen, Jiefeng; Yao, Meicun; Li, Qing
• Is Part Of: Biomedical chromatography. Volume 29:Number 5(2015:May)
• Page Start: 679
• Page End: 688
• Publication Date: 2014-10-08
• Subjects: Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.3331
• Languages: English
• ISSNs: 0269-3879

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>A simple, sensitive and specific method using ultraperformance liquid chromatography/tandem mass spectrometry (UPLC‐MS/MS) was developed to determine sunitinib and <italic>N</italic>‐desethyl sunitinib in mouse plasma and tissues. The analytes were separated by an isocratic mobile phase consisting of acetonitrile and buffer solution (water with 0.1% formic acid and 5 m <sc>m</sc> ammonium acetate; 40: 60, v/v) running at a flow rate of 0.35 mL/min for 2 min. Quantification was performed using a mass spectrometer by multiple reaction monitoring in positive electrospray ionization mode. The transition was monitored at <italic>m</italic>/<italic>z</italic> 399 → 283, <italic>m</italic>/<italic>z</italic> 371 → 283 and <italic>m</italic>/<italic>z</italic> 327 → 270 for sunitinib, <italic>N</italic>‐desethyl sunitinib and internal standard, respectively. Calibration curves were linear over concentration ranges of 2–500, 0.5–50 and 1–250 ng/mL for plasma, heart and other biosamples. The method was successfully applied to animal experiments. The pharmacokinetic study indicated that sunitinib was eliminated quickly in mice with a half‐life of 1.2 h; tissue distribution data showed more sunitinib and its metabolite in liver, spleen and lung, which provided reference for further study. Copyright © 2014 John Wiley &amp; Sons, Ltd.</p> </abstract>