Studies on metabolism of drugs. 8. On the glucuronide of sulfaphenazole in human.

Abstract

The metabolism of sulfaphenazole (SP), i.e. N1-(1-phenylpyrazole-5-yl) sulfanilamide in the human body was investigated. The main metabolite was isolated and confirmed to be the N-glucuronide of SP. In order to determine the structure of this glucuronide, SP-N1-[methyl (tri-O-acetyl-β-D-glucopyranosid) uronate] (III) was synthesized from potassium salt of SP and methyl (2, 3, 4-tri-O-acetyl-1-bromo-1-deoxy-α-D-glucopyranosid) uronate. Hydrolysis of III with NH4OH gave both N1-glucuronide and ring N-glucuronide of SP in the ratio of about 2 to 1. Furthermore, N1-methyl and ring N-methyl derivatives of SP were prepared with CH2N2, and their infrared and ultraviolet spectra were compared with those of the conjugate to confirm the substituted position of the glucuronic acid. These evidences indicated that the extracted compound is an imido-type conjugate, carrying the glucuronic acid attached to the nitrogen in the pyrazole ring while SP itself takes the amido form. Therefore, the main metabolite of SP is a sodium 1-deoxy-[1-phenyl-5-(sulfanilimino)-3-pyrazolin-2-yl]-D-glucopyranosiduronate containing 1 mole of water of crystallization.