New metabolites of the drug 5-aminosalicylic acid. II. N-formyl-5-aminosalicylic acid.
1. A new metabolite of the drug 5-aminosalicylic acid (5-ASA) has been found in urine from pigs and in plasma of humans. The metabolite has been isolated from pig urine using an XAD-2 column and purified using preparative h.p.l.c. 2. The metabolite has been identified as N-formyl-5-ASA (5-formamidosalicylic acid) using 1H- and 13C-n.m.r. spectrometry and mass spectroscopy and the structure was confirmed by chemical synthesis. 3. N-Formyl-5-ASA is stable in human plasma and in potassium phosphate buffers between pH 3.0 and 9.0. It is hydrolysed below pH 3.0. 4. N-Formyl-5-ASA was readily formed in rat liver homogenate when 5-ASA and N-formyl-L-kynurenine were added. Thus N-formyl-5-ASA might be formed by the actions of formamidase in vivo. 5. N-Formyl-5-ASA has been found in human plasma from healthy volunteers dosed i.v. with 5-ASA (250 mg). N-beta-D-glucopyranosyl-5-ASA, N-acetyl-5-ASA and N-formyl-5-ASA were quantified in human plasma using a h.p.l.c. assay.
Tjørnelund
J
J
Royal Danish School of Pharmacy, Department of Organic Chemistry, Copenhagen.
Hansen
S H
SH
Cornett
C
C
D000636:Aminosalicylic Acids / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019804:Mesalamine; D012459:Salicylates / Q000302:isolation & purification*; D013552:Swine
D000636:Aminosalicylic Acids; D012459:Salicylates; C070963:N-formamidosalicylic acid; D019804:Mesalamine