title: 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.
abstract: 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.
authors.affiliation: Pharmaceutical Analysis Laboratory, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou, 510006, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Mengping
authors.initials: M
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Liao
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Wang
authors.forename: Huajuan
authors.initials: H
authors.lastname: Du
authors.forename: Jiefeng
authors.initials: J
authors.lastname: Chen
authors.forename: Meicun
authors.initials: M
authors.lastname: Yao
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D011758:Pyrroles / Q000097:blood* / Q000493:pharmacokinetics; D000077210:Sunitinib; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D007211:Indoles; D011758:Pyrroles; C544393:SU 12662; D000077210:Sunitinib
keywords: UPLC-MS/MS; distribution; mouse; pharmacokinetics; sunitinib