Determination of metabolically derived nitroprocainamide in the urine of procainamide-dosed humans and rats by liquid chromatography with electrochemical detection.
The N-oxidized metabolites of the antiarrhythmic procainamide have previously been implicated as inciting agents in the autoimmune condition drug-related lupus. Although much data have been collected with respect to the in vitro behavior of these metabolites, relatively little has been accomplished in vivo because of their extreme reactivity. The determination of nitroprocainamide (NPA), a stable decomposition product of the reactive hydroxylamine and nitroso species, in the urine of rats dosed with procainamide is reported here using the sensitive and selective method of HPLC with electrochemical detection. For orally and i.v.-dosed animals, up to microgram amounts of NPA were excreted over 24 hr from an initial dose of 66-100 mg procainamide/kg body weight. Also, the apparent elimination of microgram quantities of NPA in the urine specimens of 9 of 11 patients undergoing treatment with procainamide was observed. This suggests that N-oxidation of the aromatic ring of procainamide is occurring at sufficient levels to result in the formation of significant amounts of the reactive hydroxylamine and nitroso metabolites in vivo, and may have direct implications in the diverse and widespread symptomatology associated with procainamide-induced drug-related lupus.
Department of Chemistry, University of Cincinnati, OH.
J F
JF
Wheeler
L E
LE
Adams
A B
AB
Mongey
S M
SM
Roberts
W R
WR
Heineman
E V
EV
Hess
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000276:immunology / Q000378:metabolism; D004563:Electrochemistry; D006801:Humans; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D008297:Male; D011342:Procainamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000652:urine; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
D007202:Indicators and Reagents; C070890:4-nitroprocainamide; D004247:DNA; D011342:Procainamide