Quantification of sunitinib in human plasma by high-performance liquid chromatography–tandem mass spectrometry

A rapid, sensitive and specific method was developed and validated using LC/MS/MS for determination of sunitinib in human plasma. Sample preparation involved a liquid–liquid extraction by the addition of 0.2 mL of plasma with 4.0 mL tert-butyl-methyl-ether extraction solution containing 25 ng/mL of the internal standard clozapine. Separation of compounds was achieved on a C18 (50 mm × 2.1 mm i.d., 3.5 μm) analytical column using a mobile phase consisting of acetonitrile/H20 (65:35, v/v) containing 0.1% formic acid and isocratic flow at 0.150 mL/min for 3 min. The analytes were monitored by tandem-mass spectrometry with electrospray positive ionization. Linear calibration curves in human plasma were generated over the range of 0.2–500 ng/mL with values for the coefficient of determination of >0.9950. Within- and between day precision and accuracy were ≤10%. The method was applied to the quantitation of sunitinib in plasma samples from a patient receiving daily oral therapy with sunitinib.