Spectrofluorimetric determination of vigabatrin and gabapentin in urine and dosage forms through derivatization with fluorescamine.

A stability-indicating, sensitive, simple and selective spectrofluorimetric method was developed for the determination of vigabatrin (VG) and gabapentin (GB). The method is based on the reaction between the two drugs and fluorescamine in borate buffer of pH 8.2 to give highly fluorescent derivatives that are measured at 472 nm using an excitation wavelength of 390 nm for both drugs. The optimum conditions were ascertained and the method was applied for the determination of VG and GB over the concentration range of 0.20-4.00 and 0.1-1.0 microg/ml, respectively with detection limits of 0.05 microg/ml (2.9 x 10(-7) M) and 0.06 microg/ml (2.3 x 10(-7) M) for VG and GB, respectively. The suggested method was applied, without any interference from the excipients, to the determination of the two drugs in their pharmaceutical formulations. Furthermore, the method was extended to the in-vitro determination of both drugs in spiked human urine. Interference from endogenous amino acids could be eliminated through selective complexation with copper acetate, the % recovery (n=4) is 98.0 +/- 7.05. Co-administered drugs such as lamotrigine, phenobarbitone, valproic acid, clopazam, carbamazepine, clonazepam and cimitidine did not interfere with the assay. The method is also stability-indicating; as the degradation product of vigabatrin: 5-vinylpyrrolidin-2-one, produced no interference with its analysis.

Determination of vigabatrin in human plasma and urine by high-performance liquid chromatography with fluorescence detection.

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 microg/ml for plasma and 1.0-15.0 microg/ml for urine with a lower limit of detection of 0.1 microg/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.

Determination of the antiepileptics vigabatrin and gabapentin in dosage forms and biological fluids using Hantzsch reaction.

A selective and sensitive method was developed for the determination of the anticonvulsants vigabatrin (I) (CAS 60643-86-9) and gabapentin (II) (CAS 60142-96-3). The method is based on the condensation of the drugs through their amino groups with acetylacetone and formaldehyde according to Hantzsch reaction yeilding the highly fluorescent dihydropyridine derivatives. The yellowish-orange color was also measured spectrophotometrically at 410 nm and 415 nm for I and II, respectively. The absorbance-concentration plots were rectilinear over the ranges 10-70 micrograms/ml and 20-140 micrograms/ml for I and II, respectively. As for the fluorescence-concentration plots, they were linear over the ranges 0.5-10 micrograms/ml and 2.5-20 micrograms/ml with minimum detection limits (S/N = 2) of 0.05 microgram/ml (approximately 2.1 x 10(-8) mol/l) and 0.1 microgram/ml (approximately 5.8 x 10(-7) mol/l) for I and II, respectively. The spectrophotometric method was applied to the determination of I and II in their tablets. The percentage recoveries +/- SD (n = 6) were 99.45 +/- 0.13 and 98.05 +/- 0.53, respectively. The spectrofluorimetric method was successfully applied to the determination of I and II in spiked human urine and plasma. The % recoveries +/- SD (n = 5) were 98.77 +/- 0.29 and 98.39 +/- 0.53 for urine and 99.32 +/- 0.74 and 98.90 +/- 0.96 for plasma, for I and II, respectively. No interference was encountered with the co-administered drugs: valproic acid (CAS 99-66-1), diphenylhydantoin (CAS 57-41-0), phenobarbital (CAS 50-06-6), carbamazepine (CAS 298-46-4), clonazepam (CAS 1622-61-3), clobazam (CAS 22316-47-8) or cimetidine (CAS 51481-61-9). A proposal of the reaction pathway is suggested. The advantages of the proposed methods over existing method are discussed.