Identification of oxidation products of 5-aminosalicylic acid in faeces and the study of their formation in vitro.
The formation of three oxidant-derived products of 5-aminosalicylic acid (5-ASA) in vivo was demonstrated in patients with active ulcerative colitis as well as in healthy subjects. The products were isolated from faeces by preparative HPLC and their chemical structures were found to be oxidation products of 5-ASA using 1H-NMR spectroscopy and mass spectrometry. Reactions carried out in vitro between 5-ASA and oxidants suggested to be present in the inflamed bowel verified that the hypochlorite-mediated oxidation of 5-ASA as well as the haemoglobin-catalysed H2O2-dependent oxidation of 5-ASA resulted in the formation of a single oxidation product of 5-ASA. This product was similar to, but not identical to any of the products identified in faeces from patients receiving 5-ASA. Oxygen radical-mediated oxidation of 5-ASA gave several products, different from the products isolated. Finally, it was verified that the products formed in vivo are not formed as a result of autooxidation of 5-ASA either in faeces extract or in pharmaceuticals.
Jensen
J
J
Department of Organic Chemistry, Royal Danish School of Pharmacy, Denmark.
Cornett
C
C
Olsen
C E
CE
Bondesen
S
S
Christensen
J
J
Christensen
L A
LA
Tjørnelund
J
J
Hansen
S H
SH
D000636:Aminosalicylic Acids / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism; D005243:Feces / Q000737:chemistry*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D006997:Hypochlorous Acid; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019804:Mesalamine; D010084:Oxidation-Reduction; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000636:Aminosalicylic Acids; D006454:Hemoglobins; D006878:Hydroxides; D019804:Mesalamine; D006997:Hypochlorous Acid; C031356:hydroxide ion; D006861:Hydrogen Peroxide