New metabolites of the drug 5-aminosalicylic acid. II. N-Formyl-5-aminosalicylic acid

Abstract

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-β-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.