INVITRO METABOLISM OF THE ANTIMALARIAL AGENT PRIMAQUINE BY MOUSE-LIVER ENZYMES AND IDENTIFICATION OF A METHEMOGLOBIN-FORMING METABOLITE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (1) , 35-44
Abstract
From a mouse liver microsomal system, methemoglobin-forming metabolite of primaquine (PQ) was isolated and identified. Both O-dealkylation and hydroxylation of PQ evidently formed a metabolite, 5,6-dihydroxy-8-(4-amino-1-methylbutylamino)quinoline, which is highly active in forming methemoglobin in both normal and glucose-6-phosphate dehydrogenase-deficient erythrocytes. It also actively decreases glutathione levels in glucose-6-phosphate dehydrogenase-deficient erythrocytes. The inhibitor SKF525-A [proadifen hydrochloride] prevented metabolite formation while iproniazid and CO did not inhibit metabolism completely but may have resulted in formation of a different unidentified metabolite. Mass spectrometry, HPLC [high-performance liquid chromatography], NMR, and other more indirect methods were used to help identify the metabolite. It was identified indirectly via a blue compound which results from extracting the actual metabolite from the incubation mixture with organic solvents under alkaline conditions in the presence of light. The blue compound was identified as a quinonimine in which the 8-amino side chain of PQ cyclizes to produce a 3rd ring system.