High-performance liquid chromatographic studies of reaction of hydralazine with biogenic aldehydes and ketones.

To understand hydrazone formation in hydralazine metabolism, the reaction of hydralazine with various biogenic aldehydes and ketones (acetone, pyruvic acid, acetoacetic acid, formaldehyde, and acetaldehyde) in pH 7.4 buffer was studied for potential alterations in hydralazine pharmacokinetics secondary to alcoholism and diabetes. The corresponding hydrazones were isolated, and their structures were characterized. High-performance liquid chromatography was used to monitor the reactions. An aqueous solvent reversed-phase liquid chromatographic system was used to separate hydralazine and its derivatives. Reaction of hydralazine with formaldehyde or acetaldehyde produced the corresponding hydrazones. Formation of an s-triazolo ring system yielded the known s-triazolo[3,4-alpha]phthalazine and 3-methyl-s-triazolo[3,4-alpha]phthalazine metabolites, which also were isolated and characterized and suggested nonenzymatic metabolism.