Till date, no analytical method published to detect Cisplatin has been validated according to the U.S. Food and Drug Administration (FDA) guidance using liquid chromatography mass spectrometry (LC-MS/MS). We report, a validated LC-MS/MS method for quantitative determination of cisplatin in rat plasma and urine according to FDA guidlines. Cisplatin is a platinum containing compound used for the treatment of different types of cancers. Quantitative determination of cisplatin has been carried out using atomic absorption spectroscopy, high pressure liquid chromatography with phosphorescence, ultra-violet detection, or with inductively coupled plasma mass spectrometry. Few LC-MS/MS methods have been reported for the analysis of cisplatin either for direct quantification or indirect by derivatizing with organic compounds but none of the reported methods have validated the method. The developed and validated assay presented here is a highly sensitive LC-MS/MS method developed and validated for the quantitative determination of cisplatin following derivatization with diethyldithiocarbamate (DDTC) in order to detect platinum (Pt) of cisplatin, suitable for pharmacokinetic studies in rats and to further use it to study human toxicology. Chromatographic separation was achieved using a Poroshell 120 EC-C18 column (3×50mm, 2.7μm) with a binary gradient mobile phase. Quantification was performed on a triple quadruple with electrospray ionization and detection was performed using multiple reaction monitoring. The method has a limit of detection of 1ng/mL, and the quantifiable range was 3-3000ng/mL in rat plasma and urine. The method was accurate and precise with an accuracy and precision for intra-day and inter-day of ±20% for lower limit of quantitation and of ±15% for low, mid and high quality control samples. This method was successfully applied to study the pharmacokinetic profile of cisplatin in rat plasma and urine given a range of doses from 0.5 to 3.5mg/kg.
Keywords: Cisplatin; Cisplatin derivatization with DDTC; Cisplatin rat pharmacokinetics; FDA method validation; LC–MS/MS; Non-compartmental analysis of cisplatin.
Published by Elsevier B.V.