Abstract:
:The reactions of omeprazole, a potent proton pump inhibitor (PPI), were investigated in the absence of a nucleophile. Reactions were monitored, using differential pulse polarography (DPP) at the static mercury drop electrode (SMDE), in solutions buffered to pH values ranging from 2.0 to 8.0. The fast, sensitive, and selective electrochemical technique facilitated to repeat recordings of successive voltammograms [peak current (nA) vs. peak potential (volts vs. Ag/AgCl saturated with 3.0 M KCl)]. The DPP signals of omeprazole and its degradation products, believed to be due to sulfur functional group (the principal site of electrode reaction), gave advantages over the previously employed UV detection technique. The latter primarily relied on pyridine and benzimidazole analytical signals, which are common reaction products of PPI in aqueous acidic solutions. After peak identification, the resulting current (nA)-time (s) profiles, demonstrated that omeprazole undergoes degradation to form two main stable compounds, the first is the cyclic sulfenamide (D(+)), previously believed to be the active inhibitor of the H(+), K(+)-ATPase, the second is omeprazole dimer. This degradation is highly dependant on pH. Unlike previous studies which reported that the lifetime of D(+) is few seconds, the cyclic sulfenamide (D(+)) was found to be stable for up to 5-20 min. The results further indicated that omeprazole converts into the cyclic sulfenamide in an irreversible reaction, consequently, D(+) and sulfenic acid (an intermediate which rapidly converts into D(+)) were not interconvertable. The present work suggested that the sulfenic acid is the active inhibitor in vivo. In addition, the omeprazole reactions, in the absence of the thiol, were not as complicated as were previously reported.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Qaisi AM,Tutunji MF,Tutunji LFdoi
10.1002/jps.20546subject
Has Abstractpub_date
2006-02-01 00:00:00pages
384-91issue
2eissn
0022-3549issn
1520-6017pii
S0022-3549(16)31955-4journal_volume
95pub_type
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