title: High sensitivity determination of valproic acid in mouse plasma using semi-automated sample preparation and liquid chromatography with tandem mass spectrometric detection.
abstract: A high-throughput liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) assay using automated sample preparation has been developed for the determination of valproic acid (VPA) in mouse plasma. A liquid-handling system was programmed to prepare calibration standard solutions in plasma, as well as quality controls and clinical samples. Plasma protein precipitation was performed on a 96-well plate, and the collected supernatant was directly injected into a reversed-phase LC/ESI-MS/MS system in the negative ionization mode. The calibration curve for VPA was linear over a dynamic range of 0.15-100 microg/mL. The limit of detection was 75 ng/mL and the lower limit of quantitation was 150 ng/mL. Intra- and inter-day validation assays of the semi-automated plasma analysis showed satisfactory accuracy and precision.
authors.affiliation: Istituto di Ricerche di Biologia Molecolare P. Angeletti, Merck Sharp and Dohme Research Laboratories, Via Pontina km 30.600, 00040 Pomezia, Roma, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pucci
authors.forename: Edith
authors.initials: E
authors.lastname: Monteagudo
authors.forename: Fabio
authors.initials: F
authors.lastname: Bonelli
mesh_terms: D000818:Animals; D001331:Automation; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D012680:Sensitivity and Specificity; D014635:Valproic Acid / Q000097:blood*
chemical_list: D014635:Valproic Acid