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Validated HILIC-MS/MS assay for determination of vindesine in human plasma: Application to a population
Rong-Hua Zhu1, Huan-De Li2, Hua-Lin Cai2
1Clinical Pharmacy and Pharmacology Research Institute, the Second Xiang-Ya Hospital, Central-South University, Changsha, Hunan Province 410011, People's Republic of China; School of Pharmacy, Central-South University, Changsha 410005, People's Republic of China.
Abstract:
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.
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