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.
al-Zehouri
J
J
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
al-Madi
S
S
Belal
F
F
D000085:Acetates / Q000032:analysis* / Q000097:blood / Q000652:urine; D000588:Amines; D000927:Anticonvulsants / Q000032:analysis* / Q000097:blood / Q000652:urine; D003509:Cyclohexanecarboxylic Acids; D005456:Fluorescent Dyes; D000077206:Gabapentin; D006801:Humans; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets; D020888:Vigabatrin / Q000032:analysis* / Q000097:blood / Q000652:urine; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005456:Fluorescent Dyes; D013607:Tablets; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin