Characterization of the urinary metabolites of primaquine in rats.

Following the synthesis of reference standards of the primaquine metabolites, a high-performance liquid chromatographic (HPLC) analytical method for carboxyprimaquine, its glycine conjugate, and its glucuronide conjugate in urine samples was developed. After the administration of primaquine, only trace quantities of primaquine and carboxyprimaquine (each less than 1% of dose) and no significant quantity of the two conjugates of carboxyprimaquine were excreted in the urine. When carboxyprimaquine was administered, only 0.3% of the dose was excreted in the urine. When carboxyprimaquine glycinate was administered, the compound was found in the 700- to 1300-µg/ml concentration range in the urine within the first few hours. Using (14)C-labeled primaquine, six new metabolites were found in the urine and partially characterized. The purported metabolites of primaquine (8-amino-6-methoxyquinoline, 5-hydroxyprimaquine, and 6-desmethyl-5-hydroxyprimaquine) were not found in the urine. A field screening test for the quantitation of primaquine metabolites in urine was also investigated. The inexpensive, but sensitive assay was found to give results that closely paralleled the more complex HPLC method and it was moderately well correlated with the total radioactivity in the urine samples.