title: An automated method for the bioanalysis of vincristine suitable for therapeutic drug monitoring and pharmacokinetic studies in young children.
abstract: Pharmacokinetic studies in young children require very sensitive methods using low plasma volumes. Although vincristine has been used as an antineoplastic drug for almost 40 years, data on vincristine pharmacokinetics and pharmacodynamics are scarce, especially in young children. One of the reasons for this is the lack of a specific and sensitive assay suitable for small plasma volumes. Therefore the authors aimed to improve an existing high-performance liquid chromatography (HPLC) assay by changing the solid-phase extraction material and by using a more sensitive and controlled electrochemical detector. An on-line solid-phase extraction was used with a preconcentration column of 10 * 3 mm ID containing octadecyl silane (ODS) reversed-phase material and an analytical microsphere C18 column. The mobile phase was unchanged and consisted of 35% phosphate buffer 0.02 mol (pH 7.00 +/- 0.10), 50% methanol, and 15% acetonitrile. Detection was performed with a new electrochemical detector. This detector comprised a highly stable Faraday-shielded oven compartment that accommodated a column and flowcell. The flowcell had a spacer thickness of 0.25 microm set at 830 mV. It also had an excellent signal-to-noise ratio, which resulted in very sensitive electrochemical analysis. These improvements resulted in a lower required sample volume of only 0.3 mL instead of 1.2 mL plasma with a very low limit of quantitation of 0.483 microg/L according to good laboratory practice (GLP) rules. The intraday coefficients of variation were 6.2% (0.483 microg/L) and 4.2% (18.4 microg/L). The interday coefficients of variation were 10.3% (0.483 microg/L) and 8.5% (18.4 microg/L).
authors.affiliation: Laboratory for Drug Analysis and Toxicology, Department of Pharmacy, Children's Cancer Center, Beatrix Children's Hospital, University Hospital Groningen, The Netherlands. d.r.a.uges@apoth.azg.nl
authors.forename: P
authors.initials: P
authors.lastname: Koopmans
authors.forename: C E
authors.initials: CE
authors.lastname: Gidding
authors.forename: S S
authors.initials: SS
authors.lastname: de Graaf
authors.forename: D R
authors.initials: DR
authors.lastname: Uges
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis* / Q000493:pharmacokinetics*; D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D004563:Electrochemistry; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014750:Vincristine / Q000032:analysis* / Q000493:pharmacokinetics*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine