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 vigaba trin enantiomers in human serum by highperformance liquid chromatograp hy. Serum is deproteinized with trichloroacetic acid and aliquots of t he supernatant are precolumn derivatized with o-phthaldialdehyde and N -acetyl-L-cysteine, resulting in the formation of diastereomeric isoin doles. Separation was achieved on a Spherisorb 3ODS2 column using a gr adient solvent program and the column eluent is monitored using fluore scence detection. L-Homoarginine was used as an internal standard. Wit hin-day precisions (C.V.; n=8) were 2.8 and 1.1%, respectively, for th e (R)-(-)- and (S)-(+)-enantiomer in serum containing 15.4 mg/l (RS)vi gabatrin. The method was linear in the 0-45 mg/l range for both enanti omers and the minimum quantitation Limit was 0.20 mg/l for (R)-(-)-vig abatrin and 0.14 mg/l for (S)-(+)-vigabatrin. No interferences were fo und from commonly coadministered antiepileptic drugs and from endogeno us amino acids. The method is suitable for routine therapeutic drug mo nitoring and for pharmacokinetic studies. (C) 1998 Elsevier Science B. V. All rights reserved.