Validated HILIC-MS/MS assay for determination of vindesine in human plasma: Application to a population pharmacokinetic study.
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.
Clinical 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. Electronic address: ubillow@yeah.net.
Rong-Hua
RH
Zhu
Clinical Pharmacy and Pharmacology Research Institute, the Second Xiang-Ya Hospital, Central-South University, Changsha, Hunan Province 410011, People's Republic of China.
Huan-De
HD
Li
Clinical Pharmacy and Pharmacology Research Institute, the Second Xiang-Ya Hospital, Central-South University, Changsha, Hunan Province 410011, People's Republic of China.
Hua-Lin
HL
Cai
Laboratory of Clinical Pharmacology, Department of Hematology, Xiang-Ya Hospital, Central-South University, Changsha 410008, People's Republic of China.
Zhi-Ping
ZP
Jiang
Clinical Pharmacy and Pharmacology Research Institute, the Second Xiang-Ya Hospital, Central-South University, Changsha, Hunan Province 410011, People's Republic of China.
Ping
P
Xu
Clinical 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.
Li-Bo
LB
Dai
Clinical Pharmacy and Pharmacology Research Institute, the Second Xiang-Ya Hospital, Central-South University, Changsha, Hunan Province 410011, People's Republic of China.
Wen-Xing
WX
Peng
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014747:Vinblastine / Q000031:analogs & derivatives / Q000737:chemistry; D014751:Vindesine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077235:Vinorelbine; D055815:Young Adult
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine; D014751:Vindesine
HILIC; MS/MS; Pharmacokinetics; Vindesine; Vinorelbine