title: Validation of an electrospray ionization LC/MS/MS method for quantitative analysis of vincristine in human plasma samples.
abstract: Vincristine is a natural vinca alkaloid widely used in paediatric cancer treatment. Vincristine pharmacokinetics has been already studied, but few data are available in paediatric populations. A sensitive and specific liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for the quantification of vincristine in plasma in order to investigate pharmacokinetics in a paediatric population. Two hundred microliters of plasma was added to vinblastine, used as internal standard. Chromatographic separation was achieved on a C8 HPLC column (Phenomenex Luna 50 mm x 2.0 mm, 3.0 microm) with a mobile phase gradient at a flow rate of 0.2 ml/min. Quantification was performed using the transition of 825.4-->765.4 (m/z) for vincristine and 811.4-->751.4 (m/z) for vinblastine. Chromatographic separation was achieved in 8 min. The limit of quantification was 0.25 ng/ml with a precision of 10.2% and an accuracy of 99.6%. The calibration curve was linear up to 50.0 ng/ml. Intra-day precision and accuracy ranged from 6.3% to 10% and from 91.9% to 100.8%, respectively. Inter-assay precision and accuracy ranged from 3.8% to 9.7% and from 93.5% to 100.5%, respectively. No significant matrix effect was observed for vincristine. A rapid, specific and sensitive LC/MS/MS method for quantification of vincristine in human plasma was developed and is now successfully applied for pharmacokinetic studies in paediatric patients.
authors.affiliation: Laboratoire de Pharmacocinétique et Toxicologie, Hôpital de la Timone, 264 rue Saint Pierre, 13385 Marseille Cedex 5, France. romain.guilhaumou@ap-hm.fr
authors.forename: Romain
authors.initials: R
authors.lastname: Guilhaumou
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
authors.forename: Angelique
authors.initials: A
authors.lastname: Rome
authors.forename: Madeleine
authors.initials: M
authors.lastname: Giocanti
authors.forename: Nicolas
authors.initials: N
authors.lastname: Andre
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
mesh_terms: D000293:Adolescent; D002648:Child; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D007275:Injections, Intravenous; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013997:Time Factors; D014747:Vinblastine / Q000097:blood / Q000737:chemistry; D014750:Vincristine / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D014750:Vincristine; D014747:Vinblastine