High-performance liquid chromatographic analysis of vigabatrin enantiomers in human serum by precolumn derivatization with o-phthaldialdehyde-N-acetyl-L-cysteine and fluorescence detection

A rapid and simple method is presented for the determination of vigabatrin enantiomers in human serum by highperformance liquid chromatography. Serum is deproteinized with trichloroacetic acid and aliquots of the supernatant are precolumn derivatized with o-phthaldialdehyde and N-acetyl-L-cysteine, resulting in the formation of diastereomeric isoindoles. Separation was achieved on a Spherisorb 3ODS2 column using a gradient solvent program and the column eluent is monitored using fluorescence detection. L-Homoarginine was used as an internal standard. Within-day precisions (C.V.; n=8) were 2.8 and 1.1%, respectively, for the (R)-(-)- and (S)-(+)-enantiomer in serum containing 15.4 mg/l (RS)vigabatrin. The method was linear in the 0-45 mg/l range for both enantiomers and the minimum quantitation Limit was 0.20 mg/l for (R)-(-)-vigabatrin and 0.14 mg/l for (S)-(+)-vigabatrin. No interferences were found from commonly coadministered antiepileptic drugs and from endogenous amino acids. The method is suitable for routine therapeutic drug monitoring and for pharmacokinetic studies. (C) 1998 Elsevier Science B.V. All rights reserved.