Isolation, identification, and synthesis of the major sulpiride metabolite in primates

The major metabolite of sulpiride, N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-sulfamoyl-2-anisamide (I), in the monkey is N-[(1-ethyl-5-oxo-2-pyrrolidinyl)methyl]-5-sulfamoyl-2-anisamide (II). It is also a metabolite in other laboratory animal species and possibly at very low levels in humans. Treatment of the urine from a monkey dosed orally with 14C-I by dry column chromatography and high-pressure liquid chromatography (HPLC) produced the major metabolite in pure form. Characterization of the purified 14C-radiolabeled metabolite by proton NMR, TLC, HPLC, and chemical ionization mass spectroscopy, along with subsequent comparison of a synthetically prepared sample, gave unequivocal structural confirmation.