title: Vigabatrin in dried plasma spots: validation of a novel LC-MS/MS method and application to clinical practice.
abstract: This paper presents a LC-MS/MS method for the determination of antiepileptic drug vigabatrin in dried plasma spots (DPS). Due to its zwitterionic chemical structure, a pre-column derivatization procedure was performed, aiming to yield enhanced ionization efficiency and improved chromatographic behaviour. Propyl chloroformate, in the presence of propanol, was selected as the best derivatization reagent, providing a strong signal along with reasonable run time. A relatively novel sample collection technique, DPS, was utilized, offering easy sample handling and analysis, using a sample in micro amount (∼5μL). Derivatized vigabatrin and its internal standard, 4-aminocyclohexanecarboxylic acid, were extracted by liquid-liquid extraction (LLE) and determined in positive ion mode by applying two SRM transitions per analyte. A Zorbax Eclipse XDB-C8 column (150×4.6mm, 5μm particle size) maintained at 30°C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550μL/min and total run time 4.5min. The assay exhibited excellent linearity over the concentration range of 0.500-50.0μg/mL, which is suitable for the determination of vigabatrin level after per os administration in children and youths with epilepsy, who were on vigabatrin therapy, with or without co-medication. Specificity, accuracy, precision, recovery, matrix-effect and stability were also estimated and assessed within acceptance criteria.
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, Belgrade, Serbia.
authors.forename: Nađa
authors.initials: N
authors.lastname: Kostić
authors.affiliation: University of Athens, School of Pharmacy, Department of Pharmaceutical Chemistry, Panepistimioupoli Zografou, Athens, Greece.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Dotsikas
authors.affiliation: University of Belgrade, Faculty of Medicine, Clinic of Neurology and Psychiatry for Children and Youth, Dr Subotića 6a, Belgrade, Serbia.
authors.forename: Nebojša
authors.initials: N
authors.lastname: Jović
authors.affiliation: University of Belgrade, Faculty of Medicine, Clinic of Neurology and Psychiatry for Children and Youth, Dr Subotića 6a, Belgrade, Serbia.
authors.forename: Galina
authors.initials: G
authors.lastname: Stevanović
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Drug Analysis, Vojvode Stepe 450, Belgrade, Serbia. Electronic address: andja@pharmacy.bg.ac.rs.
authors.forename: Anđelija
authors.initials: A
authors.lastname: Malenović
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Physical Chemistry and Instrumental Methods, Vojvode Stepe 450, Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Medenica
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000097:blood*; D002138:Calibration; D002648:Child; D002853:Chromatography, Liquid / Q000379:methods; D059788:Dried Blood Spot Testing / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D053719:Tandem Mass Spectrometry / Q000379:methods*; D020888:Vigabatrin / Q000097:blood*
chemical_list: D000927:Anticonvulsants; D020888:Vigabatrin
keywords: Chloroformates; Dried plasma spots; Mass spectrometry; Vigabatrin