Establishment of a liquid chromatographic tandem mass spectrometry method for quantification of carboplatin in rat plasma and its application to a pharmacokinetic study

Aim Carboplatin is a platinum analogue that is used in a number of chemotherapeutic regimens for solid tumors, such as lung and ovarian carcinomas. This study is to establish a LC/MS/MS method using positive electrospray ionization (ESI+) for the selective and specific determination of carboplatin in rat plasma. Methods A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC/MS/MS) for the determination of carboplatin in rat plasma has been developed, fully validated and successfully applied to the pharmacokinetic study in Wistar rats after a single intravenous administration. Carboplatin and catalpol (internal standard) were well separated by a Dikma C18 column (150 mm × 4.6 mm I.D., 5 µm) using methanol–water containing 1% formic acid (10:90, v/v) as mobile phase, with a flow rate of 0.4 mL/min. Detection was performed on a triple quadrupole mass spectrometer in selective reaction monitoring (SRM) mode. Results The ionization was optimized using ESI (+) and selectivity was achieved using MS/MS analysis, m/z 372.0→294.0 and m/z 380.2→180.1 for carboplatin and I.S., respectively. The present method exhibited good linearity over the concentration range of 25–50,000 ng·mL -1 for carboplatin in rat plasma with a lower limit of quantification of 25 ng·mL -1 . The intraand inter-day precisions were 4.94–7.58% and 8.00–13.53%, and the accuracy was ranged from −0.47 to 2.55%. No endogenous components were found to interfere with the analysis, and carboplatin was stable during the whole assay period. Conclusion The method was successfully applied to a pharmacokinetic study after an intravenous administration of carboplatin to Wistar rats with a single dose of 14.4 mg/kg. The results confirm that the assay is suitable for the pharmacokinetic study of carboplatin.