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Kinetics of omeprazole degradation in the presence of 2‐mercaptoethanol
Author(s) -
AlMatar Ali Kh.,
ElEswed Bassam,
Tutunji Maha F.
Publication year - 2008
Publication title -
international journal of chemical kinetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.341
H-Index - 68
eISSN - 1097-4601
pISSN - 0538-8066
DOI - 10.1002/kin.20307
Subject(s) - sulfenic acid , chemistry , thiol , cysteine , 2 mercaptoethanol , kinetics , nucleophile , omeprazole , inorganic chemistry , medicinal chemistry , catalysis , organic chemistry , enzyme , physics , quantum mechanics , medicine
The reactions of omeprazole, a potent proton pump inhibitor, were investigated in the presence of 2‐mercapotoethanol. Reactions were monitored in solutions buffered to pH values ranging from 2.0 to 5.0 using differential pulse polarography at the static mercury drop electrode. First‐order reaction network was proposed for all conversions. It is demonstrated that acid degradation predominates at pH values ∼2–3, whereas the reaction of sulfenic acid with the more nucleophilic thiol becomes prominent at pH values around 4–5. The acidic medium is necessary for the formation of sulfenic acid, the key intermediate believed to be the active inhibitor, but acid also converts this sulfenic acid into other degradation products that are unreactive toward thiol. The present work suggests that acid inhibition may occur at pH values higher than those previously thought. Thus, “highly acidic medium is required to achieve both accumulation and activation of omeprazole in the parietal cell, but less acidic medium is necessary for the reaction of sulfenic acid intermediate with the sulfhydryl groups of cysteine residues of H + /K + ‐ATPase proton pump in vivo.” © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 352–358, 2008