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

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 96; pp. 31 - 36
• Main Authors: Zhu, Rong-Hua, Li, Huan-De, Cai, Hua-Lin, Jiang, Zhi-Ping, Xu, Ping, Dai, Li-Bo, Peng, Wen-Xing
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05.08.2014
• Subjects: Adult; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - therapeutic use; Calibration; Chromatography, High Pressure Liquid - methods; Female; Hematologic Neoplasms - drug therapy; HILIC; Humans; Limit of Detection; Male; Middle Aged; MS/MS; Pharmacokinetics; Reference Standards; Reproducibility of Results; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization - methods; Tandem Mass Spectrometry - methods; Vinblastine - analogs & derivatives; Vinblastine - chemistry; Vindesine; Vindesine - pharmacokinetics; Vindesine - therapeutic use; Vinorelbine; Young Adult; MS/MS; Pharmacokinetics; HILIC; Vindesine; Vinorelbine
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2014.03.017

Mean plasma concentration–time profiles of intravenous injection of 3mg Vindesine Sulfate for Injection to 100 unrelated Chinese Han subjects with hematological malignant disorders. •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 15mM 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 0.3–28ng/ml and the lower limit of quantification for VDS was 0.3ng/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® (3mg of Vindesine Sulfate for Injection) to Chinese Han subjects with hematological malignant disorders.