Determination of Mitomycin C in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry and its Application for Determining Pharmacokinetics in Rat

To develop the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring mitomycin C in rat plasma, samples were processed using solid-phase extraction, with the internal standard being carbamazepine. A reversed phased C18 column was utilized for the LC-MS/MS study, and mobile phases consisting of 0.1% formic acid in acetonitrile and water were injected into it at a rate of 0.3 mL/min. Multiple reaction monitoring in positive-ion mode with precursor-product ion pairs 335.3 → 242.3 (mitomycin C) and 237.1 → 194.1 (carbamazepine) was employed to quantify the compounds. The linear range in plasma was found to be 10 to 4000 ng/mL (r2=0.992). The inter-batch and intra-batch precision were <14.3% (LLOQ: 14.7%) and 13.4% (LLOQ: 16.1%), respectively. The recovery and the matrix effect of mitomycin C in plasma were 113% and 111%, respectively. Mitomycin C was stable under the conditions of this assay method. In the end, this approach proved effective in a pharmacokinetic investigation with the intravenous and oral administration of mitomycin C to rats.