DETERMINATION OF SCICINIB, A PROMISING THIOSEMICARBAZONE ANTICANCER CANDIDATE IN RAT PLASMA BY LC-MS/MS AND ITS APPLICATION TO A PRECLINICAL PHARMACOKINETICS STUDY

A highly selective and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of scicinib, a novel thiosemicarbazone analogue and anticancer agent in rat plasma. Protein precipitation with saturated EDTA solution and methanol was selected for sample preparation, and brodimoprim was employed as the internal standard (IS). The analytes were separated on a Symmetry C18 column (200 x 4.6 mm i.d., 5 mu m) by isocratic elution with a mobile phase consisting of methanol and 0.2 mM EDTA (75:25, v/v) at a flow rate of 0.4 mL/min. After electrospray ionization, the analyte and IS were recorded under selected reaction monitoring (SRM) mode. The chosen transition was m/z 313.0 ? 267.9 for scicinib and m/z 339.0 ? 280.9 for IS, respectively. The validated linearity range is 55000 ng/mL, with the lower limit of quantitation of 5 ng/mL. The developed method was successfully applied to a pharmacokinetic study of scicinib in rats after a single intravenous administration of 5 mg/kg.