Validated LC-MS/MS method for cisplatin quantification in plasma, whole blood, and cervical cancer tissue via diethyldithiocarbamate derivatization: Clinical application in cervical cancer
The objective of this research was to establish an LC-MS/MS method with high sensitivity and selectivity for the quantification of cisplatin in human plasma, whole blood, and cervical cancer tissue samples. This approach employed diethyldithiocarbamate (DDTC) as a derivatizing agent for cisplatin, and analyte detection was conducted using the multiple reaction monitoring (MRM) mode. The method demonstrated lower limits of quantification (LLOQ) of 1 ng/mL for both plasma and tissue, while for whole blood, the LLOQ was determined to be 5 ng/mL. This method demonstrated remarkable linearity (R² >0.98), precision (coefficient of variation <15 %), accuracy (85 %-115 %), and minor matrix effects in all matrices. Stability assessments confirmed the robustness of the method under various conditions, including freeze-thaw cycles, short-term storage, and reinjection. Clinical samples from cervical cancer patients treated with intravenous 40 mg/m² cisplatin over 1 h revealed concentrations from below the LLOQ to 4250 ng/mL in plasma, 55-1673 ng/mL in whole blood, and 197-1613 ng/mL in tissue. The successful application of this method enables precise pharmacokinetic and tissue distribution studies of cisplatin, facilitating personalized dosing strategies to improve treatment outcomes for cervical cancer patients.