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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
Author(s) -
Chen Xiao,
Wang Zhong,
Liu Mengping,
Liao Min,
Wang Xinfeng,
Du Huajuan,
Chen Jiefeng,
Yao Meicun,
Li Qing
Publication year - 2015
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3331
Subject(s) - chemistry , sunitinib , chromatography , selected reaction monitoring , pharmacokinetics , formic acid , metabolite , protein precipitation , bioanalysis , electrospray ionization , ammonium acetate , mass spectrometry , active metabolite , high performance liquid chromatography , tandem mass spectrometry , pharmacology , biochemistry , medicine , renal cell carcinoma , oncology
A simple, sensitive and specific method using ultraperformance liquid chromatography/tandem mass spectrometry (UPLC‐MS/MS) was developed to determine sunitinib and N ‐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 m 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 m / z 399 → 283, m / z 371 → 283 and m / z 327 → 270 for sunitinib, N ‐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 & Sons, Ltd.