760 (2001) 207–212 Journal of Chromatography B, www.elsevier.com / locate / chromb Determination of vigabatrin in human plasma and urine by high-performance liquid chromatography with fluorescence detection * Sidika Erturk, Esra S. Aktas, Sedef Atmaca University of Istanbul, Faculty of Pharmacy, Department of Analytical Chemistry, Beyazit, 34452 Istanbul, Turkey Received 7 December 2000; received in revised form 27 April 2001; accepted 22 May 2001 Abstract A sensitive and specific HPLC method has been developed for the assay of vigabatrin in human plasma and urine. The assay involves derivatization with 4-chloro-7-nitrobenzofurazan, solid-phase extraction on a silica column and isocratic reversed-phase chromatography with fluorescence detection. Aspartam was used as an internal standard. The assay was linear over the concentration range of 0.2–20.0 mg/ml for plasma and 1.0–15.0 mg/ml for urine with a lower limit of detection of 0.1 mg / ml using 0.1 ml of starting volume of the sample. Both the within-day and day-to-day reproducibilities and accuracies were less than 5.46% and 1.6%, respectively. After a single oral dose of 500 mg of vigabatrin, the plasma concentration and the cumulative urinary excretion of the drug were determined.  2001 Elsevier Science B.V. All rights reserved. Keywords: Vigabatrin; 4-chloro-7-nitrobenzofurazan 1. Introduction sion. The absorption characteristics of the enantio- mers are similar to those of the racemate. Vigabatrin A new antiepileptic drug vigabatrin ( g-vinyl-g- is rapidly absorbed from the gastrointestinal tract amino butyric acid) is a structural analogue of the reaching peak plasma concentrations within 1 to 2 h inhibitory neurotransmitter g-amino butyric acid after oral administration. It has a favourable phar- (GABA). Its action is attributed to the irreversible macokinetic profile since it has little protein-binding, inhibition of GABA-transaminase, an enzyme re- is mainly excreted by the kidney and has a long sponsible for the degradation of GABA [1]. By effective elimination half-life (5–7 h) allowing once increasing brain concentrations of GABA, vigabatrin or twice daily dosing [3]. appears to decrease propagation of abnormal hyper- Measurement of plasma vigabatrin concentrations synchronous discharges, thereby reducing seizure is useful in assessing compliance and evaluating activity [2]. risks of toxicity [3,4]. Several methods for the assay The commercially available drug is a racemic of vigabatrin in biological fluids have been reported. mixture, but only the S( 1)-enantiomer is pharmaco- Grove et al. [5] described the analysis of vigabatrin logically active and does not undergo chiral inver- using an amino acid analyser with microcolumns and fluorimetric detection. This is a time consuming method requiring regeneration of the column after *Corresponding author. Fax: 190-212-5190-812. E-mail address: satmaca@superonline.com (S. Atmaca). each analysis. Two gas chromatographic methods 0378-4347 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved. PII: S0378-4347(01)00268-7