Identification of oxidation products of 5-aminosalicylic acid in faeces and the study of their formation in vitro

J. Jensen; Claus Cornett; C. E. Olsen; S. Bondesen; J. Christensen; L. A. Christensen; J. Tjornelund; S. H. Hansen

Identification of oxidation products of 5-aminosalicylic acid in faeces and the study of their formation in vitro

J. Jensen, Claus Cornett, C. E. Olsen, S. Bondesen, J. Christensen, L. A. Christensen, J. Tjornelund, S. H. Hansen

12 Citations (Scopus)

Abstract

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 is 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 H-1-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.

Original language	Undefined/Unknown
Journal	Biochemical Pharmacology
Volume	45
Issue number	6
Pages (from-to)	1201-1209
Number of pages	9
ISSN	0006-2952
Publication status	Published - 1993

Cite this

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title = "Identification of oxidation products of 5-aminosalicylic acid in faeces and the study of their formation in vitro",

abstract = "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 is 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 H-1-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.",

keywords = "metabolites sulfasalazine olsalazine hemoglobin mechanism damage",

author = "J. Jensen and Claus Cornett and Olsen, {C. E.} and S. Bondesen and J. Christensen and Christensen, {L. A.} and J. Tjornelund and Hansen, {S. H.}",

year = "1993",

language = "Udefineret/Ukendt",

volume = "45",

pages = "1201--1209",

journal = "Biochemical Pharmacology",

issn = "0006-2952",

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number = "6",

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TY - JOUR

T1 - Identification of oxidation products of 5-aminosalicylic acid in faeces and the study of their formation in vitro

AU - Jensen, J.

AU - Cornett, Claus

AU - Olsen, C. E.

AU - Bondesen, S.

AU - Christensen, J.

AU - Christensen, L. A.

AU - Tjornelund, J.

AU - Hansen, S. H.

PY - 1993

Y1 - 1993

N2 - 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 is 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 H-1-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.

AB - 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 is 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 H-1-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.

KW - metabolites sulfasalazine olsalazine hemoglobin mechanism damage

M3 - Tidsskriftartikel

SN - 0006-2952

VL - 45

SP - 1201

EP - 1209

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

IS - 6

ER -