Validated HILIC–MS/MS assay for determination of vindesine in human plasma: Application to a population pharmacokinetic study

•HILIC separation mode coupled to ESI-MS/MS was used for quantitative analysis.•The analytes of interest were well separated with sharp and symmetrical peak shapes.•The method is simple, sensitive, good specificity, robust and time efficient.•Successfully applied to a population pharmacokinetic study in Chinese Han subjects with hematological malignant disorders.

The first HILIC–tandem mass spectrometry (MS/MS) method for determination of vindesine (VDS) in human plasma using vinorelbine as an internal standard (IS) has been developed and validated. Plasma samples clean-up consisted of solid phase extraction with a strata™-X column. The compounds were separated on a HILIC column with an isocratic mobile phase consisting of acetonitrile and 15 mM ammonium acetate buffer containing 0.15% formic acid (80:20, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer via electrospray positive ionization (ESI+). The ion transitions recorded in multiple reaction monitoring mode were m/z 754.6 → 123.8 for VDS and 779.4 → 323.3 for IS, respectively. Linear calibration curves were obtained in the concentration range of 0.3–28 ng/ml and the lower limit of quantification for VDS was 0.3 ng/ml. The coefficient of variation of the assay precision was less than 13%, and the accuracy exceeded 96%. The developed assay method was successfully applied for the evaluation of population pharmacokinetics of VDS after intravenous infusion of Xi Ai Ke Vial® (3 mg of Vindesine Sulfate for Injection) to Chinese Han subjects with hematological malignant disorders.

Graphical abstractMean plasma concentration–time profiles of intravenous injection of 3 mg Vindesine Sulfate for Injection to 100 unrelated Chinese Han subjects with hematological malignant disorders.Figure optionsDownload full-size imageDownload as PowerPoint slide