Validation of an UPLC-MS-MS Method for Quantitative Analysis of Vincristine in Human Urine After Intravenous Administration of Vincristine Sulfate Liposome Injection

摘要

Vincristine sulfate liposome injection (VSLI) is a liposomal formulation of vincristine (VCR) sulfate, being developed for the systemic treatment of cancer. In this paper, we have developed and validated a method to quantify VCR in human urine to obtain the urinary excretion of VCR after intravenous administration of VSLI. The analyte was extracted from urine samples using liquid-liquid extraction after addition of vinblastine (VBL, used as internal standard) and chromatographed on an Acquity UPLC HSS T3 column with a gradient mobile phase at a flow rate of 0.4 mL/min. The multiple reactions monitoring transitions of m/z 413.2 -> 353.2 and m/z 406.2 -> 271.6 were used to quantify VCR and VBL, respectively. The lower limit of quantification was 0.5 ng/mL with a precision (RSD%) of 5.7% and an accuracy (RE%) of 6.7%. The calibration curve was linear up to 100.0 ng/mL. Intraday precision and accuracy ranged from 0.8 to 11.0% and from -212.4 to 11.3%, respectively. Interassay precision and accuracy ranged from 8.0 to 10.1% and from -7.7 to 3.6%, respectively. No significant matrix effect was observed for VCR. The method was successfully applied for pharmacokinetic study of VSLI to investigate the route and extent of VCR urinary excretion in Chinese subjects with lymphoma.