@article {Budinsky37, author = {R A Budinsky and S M Roberts and E A Coats and L Adams and E V Hess}, title = {The formation of procainamide hydroxylamine by rat and human liver microsomes.}, volume = {15}, number = {1}, pages = {37--43}, year = {1987}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {A method is described, using HPLC and electrochemical detection, which permits the direct quantitation of procainamide hydroxylamine. Procainamide hydroxylamine was formed from procainamide by hepatic microsomes from both rat and human, with rat microsomes showing higher apparent formation rates. The apparent Km for formation of procainamide hydroxylamine was 0.044 mM for rat liver microsomes, with an apparent Vmax of 2.81 nmol/min/mg of protein. Estimates of Km from three human microsomal samples were 6.29, 2.89, and 6.88 mM. Vmax estimates were 0.31, 0.74, and 0.74 nmol/min/mg of protein, respectively, roughly an order of magnitude less than that observed for the rat. Microsomal formation in both species was inhibited by boiling the microsomes, eliminating NADPH from the incubation system, by preincubation with SKF 525A, cimetidine, or n-octylamine, or by gassing the microsomal incubation mixture with carbon monoxide. These observations suggest that procainamide hydroxylamine formation is cytochrome P-450 mediated. Procainamide hydroxylamine could not be detected in the blood of rats treated with a single dose of procainamide, 100 mg/kg, po. One potential reason for the inability to detect this metabolite in blood is indicated by the rapid disappearance in vitro of procainamide hydroxylamine added to whole blood. Most of this disappearance appears to be due to an interaction with hemoglobin.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/15/1/37}, eprint = {https://dmd.aspetjournals.org/content/15/1/37.full.pdf}, journal = {Drug Metabolism and Disposition} }