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

Vincristine sulfate liposome injection (VSLI) is a liposomal formula-tion 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 excre-tion of VCR after intravenous administration of VSLI. The analyte was extracted from urine samples using liquid – liquid extraction after ad-dition of vinblastine (VBL, used as internal standard) and chromato-graphed 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 quantifica-tion 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 27.7 to 3.6%, respectively. No significant matrix effect was observed for VCR. The method was suc-cessfully applied for pharmacokinetic study of VSLI to investigate the route and extent of VCR urinary excretion in Chinese subjects with lymphoma