Gradient Elution LC-MS Determination of Dasatinib in Rat Plasma and Its Pharmacokinetic Study

A sensitive and simple liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method for determination of dasatinib in rat plasma using one-step protein precipitation was developed. After addition of carbamazepine as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on an SB-C18 (2.1 mm x 150 mm, 5 mu m) column with methanol-0.1% formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; selective ion monitoring (SIM) mode was used to quantification using target fragment ions m/z 488.2 for dasatinib and m/z 338.7 for the IS. Calibration plots were linear over the range of 10-1000 ng mL(-1) for dasatinib in rat plasma. Lower limit of quantification (LLOQ) for dasatinib was 10 ng mL(-1). Mean recovery of dasatinib from plasma was in the range 82.2%-93.6%. Relative standard deviation (RSD) of intra-day and inter-day precision were both less than 8%. This developed method is successfully used in pharmacokinetic study of dasatinib in rats.