Identification of 5-ethyl-5-(2-methylbutyl)barbituric acid as an impurity of manufacture in amobarbital.
Amobarbital [5-ethyl-5-(3-methylbutyl)barbituric acid], USP, was found to contain an impurity that was not associated with hydrolysis and decomposition of the barbiturate ring. The impurity was isolated by semipreparative HPLC and was identified as 5-ethyl-5-(2-methylbutyl)barbituric acid (1) by MS (electron impact and chemical ionization) and 1H NMR. The substitution pattern on the alkyl side chain was verified by using the achiral NMR shift reagent tris(6,6,7,7,8,8,8-heptafluoro-2,2- dimethyl-3,5-octanedionato)europium(III). Older samples of amobarbital, USP, contained greater than 6% of 1, whereas recent samples of amobarbital, USP, contained less than 1% of 1. Because the pharmacological profiles of 1 and amobarbital in rodents are comparable, the impurity probably does not constitute a clinically significant problem for humans.
Soine
W H
WH
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0581.
Graham
R M
RM
Soine
P J
PJ
D000654:Amobarbital / Q000032:analysis* / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
C076128:5-ethyl-5-(2-methylbutyl)barbituric acid; D000654:Amobarbital