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.

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.