HPLC analysis of microsomal metabolism of K-48

SUMMARY K-27 and K-48, bisquaternary pyridinium aldoximes differing only in the number of methyl units in the alkyl bridges between the two quaternary nitrogen atoms, are promising candidates for use as potent and effective antidotes to organophosphate intoxication. K-27 and K-48 were treated with rat hepatic microsomal preparations from healthy (control) and diabetic animals. Microsomal metabolism was measured at different times up to 45 min. This treatment resulted in a decrease of approximately 30% in the concentration of K-48 whereas that of K-27 was unchanged. There was no significant difference between the effects of microsomal preparations from control and diabetic rat liver. K-27 and K-48 in a variety of media were analysed by reversedphase HPLC with both ultraviolet and electrochemical detection. The method was validated by the usual procedures.