A highly sensitive and specific method is proposed for the determination of vigabatrin (I) and gabapentin (II) in their dosage forms and spiked human plasma. The method is based on coupling the drugs with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole in borate buffer at pH 7.1 and measuring the resulting fluorescence at 532 nm after excitation at 465 nm. The fluorescence intensity was a linear function of the concentration of the drugs over the ranges of 1.3-6.5 and 1.7-8.5 microg/mL for I and II, respectively. Minimum detectability values were 0.54 microg/mL (4.2 x 10(-6)M) and 0.97 microg/mL (5.7 x 10(-6)M) for I and II, respectively, under the described conditions. The proposed method was successfully applied to the determination of the 2 drugs in their dosage forms, and the percent recoveries +/- standard deviation (SD) were 104.53 +/- 1.2 and 100.00 +/- 1.32 of the label claim for I and II, respectively. The method was further applied to the determination of vigabatrin in spiked plasma samples. The percent recovery +/- SD was 101.58 +/- 2.68. Interference from endogenous alpha-amino acids was overcome through selective complexation with freshly prepared Cu(OH)2. The interference likely to be encountered from co-administered drugs, such as carbamazepine, cimetidine, clonazepam, clopazam, phenobarbital, valproic acid, and lamotrigine, was also studied. A reaction pathway is suggested.