title: Rapid and sensitive determination of vinorelbine in human plasma by liquid chromatography-tandem mass spectrometry and its pharmacokinetic application.
abstract: Vinorelbine is a semi-synthetic vinca alkaloid with demonstrated high activities against various types of advanced cancer. To support a clinical pharmacokinetic study, a simple, rapid and sensitive method to determine vinorelbine in human plasma was developed using reversed phase liquid chromatography (LC) coupled with electrospray ionization mass spectrometry/mass spectrometry (ESI-MS/MS). Vinorelbine and vinblastine (the internal standard) were extracted from human plasma by one-step liquid-liquid extraction (LLE) with methyl-t-butyl ether. The chromatographic separation was achieved on a Spursil polar-modified C(18) column (50 mm×2.1 mm, 3 μm, Dikma Technologies) with an isocratic mobile phase of a 75:25 (v/v) acetonitrile-4 mmol/L ammonium formate (pH 3.0) mixture at a flow-rate of 0.4 mL/min. The MS/MS detection was performed in the positive ion multiple reaction monitoring (MRM) mode by monitoring the precursor→product ion transitions at m/z 779.4→122.0 and m/z 811.3→224.2 for vinorelbine and the internal standard, respectively. The assay was validated in the range 0.1-200 ng/mL (r>0.997), the lowest level of this range being the lower limit of quantification (LLOQ) based on 50 μL of plasma. The intra- and inter-day precisions were within 6.0%, while the accuracy was within ±4.7% of nominal values. Detection and quantification of both analytes within 2 min make this method suitable for high-throughput analyses. The method was successfully applied to evaluate the systemic pharmacokinetics of vinorelbine after a 20-min intravenous infusion of 25 mg/m(2) of vinorelbine to patients with metastatic breast cancer.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jialei
authors.initials: J
authors.lastname: Wang
authors.forename: Xichun
authors.initials: X
authors.lastname: Hu
mesh_terms: D000097:Acetonitriles; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D005591:Chemical Fractionation; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D004355:Drug Stability; D005260:Female; D005561:Formates; D006801:Humans; D016018:Least-Squares Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000077235:Vinorelbine
chemical_list: D000097:Acetonitriles; D000972:Antineoplastic Agents, Phytogenic; D005561:Formates; C030544:formic acid; D014747:Vinblastine; D000077235:Vinorelbine; C032159:acetonitrile