A study of the differential pulse polarographic and stripping voltammetric behavior of the H⁺/K⁺ ATPase inhibitor SK&F 95601 and its degradation products

Abstract

The differential pulse polarographic (DPP) behavior of SK&F 95601 (I) has been studied in the pH range 0 to 14. At pH I 2 , (I) rapidly degrades into the sulfenamide (D:) and sulfide (DS), which are both reduced by 2e-processes, the former being subject to strong reactant adsorption. SK&F 95601 itself is reduced in a 4e process up to pH10, and either pK2 or pK, values, determined spectrophotometrically, are manifested polarographically at neutral pH A pK, value of 9.0 corresponding to the benzimidazole N-H group deprotonation is manifested polarographicallp with a pK5 value of ca. 11. SK&F 95601 and its degradation products D;, degraded D:, and DS can all be determined by adsorptive stripping voltammetry (AdSV) with limit of detections (LODs) of lo-' mol dm-3, except for the latter molecule with an LOD of lo--mol dm-3. These LODs are superior to those determined by DPP. Mixtures of these molecules can also be resolved with similar LODs. Cd" can be determined by ASV with a superior LOD in the presence of (I), i.e., 0.08 ppb as compared to 0.57 ppb in its absence, due to chelation phenomena. KEY WORDS: ATPase inhibitor, Stripping voltammetry, Pulse voltammetry lATRODUCTIONThe H+'/K+ ATPase inhibitor such as SK&F 95601 (I) is effective in stomach ulcer treatment due to its acid-catalyzed rearrangement to form the sulfenamide (D:), which then irreversibly inhibits the H+/K+ AWase enzyme, part of the "proton pump" located in the parietal cell of the stomach wall, by reaction with a thiol residue [ 1-31. Earlier articles in this series [4,5] have primarily shown the utilization of W spectrophotometry, high-performance liquid chromatography and differential pulse polarography to monitor the degradation of (I) and the structurally related omeprazole in acidic solutions pH2 and also the reactions of these benzimidazole sulfoxides with 2-mercaptoethanol in acidic solutions pH2 as a mimic of their believed reactions in vivo. This article concentrates on the differential pulse polarographic (DPP) and stripping voltammetric behavior of (I) and its degradation products such as D: and D: , which results in methods for their determination at nanomolar concentration levels. The interaction of heavy metal ions such as Cd2+ with (I) has also been investigated, which has resulted

A study of the stripping voltammetric behavior of selected metal chelates and its application to automated analysis of river waters

“…To date, no detailed investigation has been carried out on the metal complexes of 11 and 111. In the presence of I1 the response for Cd is increased by some five times as compared with that achieved in the absence of the drug [31]. The mechanism is believed to be similar to that which occurs for Zn in the presence of DMTD.…”

“…I1 and 111, their degradation reactions a t p H 2 and the subsequent reactions of these products with thiol have been studied by pulse polarography, stripping voltammetry and other n Scheme 2 Scheme 3 analytical techniques [31,33,341. To date, no detailed investigation has been carried out on the metal complexes of 11 and 111.…”