Chiral separation in the class of proton pump inhibitors by chromatographic and electromigration techniques: An overview

Abstract

Chiral separation in the class of proton pump inhibitors by chromatographic and electromigration techniques: An overviewProton pump inhibitors (PPIs) are benzimidazole-derivative chiral sulfoxides, frequently used in the treatment of gastric hyperacidity-related disorders. Due to their stereoselective metabolism, the eutomeric forms of PPIs can present a more advantageous pharmacokinetic profile by comparison with the distomers or racemates. Moreover, two representatives of the class are used in therapy both as racemates and as pure enantiomers (esomeprazole, dexlansoprazole). A relatively large number of enantioseparation methods employed for the stereoselective determination of PPIs from pharmaceutical, biological, and environmental matrices were published in the past three decades. The purpose of the current overview is to provide a systematic survey of the available chiral separation methods published since the introduction of PPIs in the therapy up to the present. Analytical and bioanalytical methods using different chromatographic and electromigration techniques reported for the enantioseparation of omeprazole, lansoprazole, pantoprazole, rabeprazole, ilaprazole, and tenatoprazole are included. The analytical conditions of the presented methods are summarized in three comprehensive tables, while a critical discussion of the applied techniques, possible mechanism of enantiorecognition, and future perspectives on the topic are also presented.

Formulation of Dosage Forms with Proton Pump Inhibitors: State of the Art, Challenges and Future Perspectives

“…Another aspect of the PPIs analysis is the chiral separation of a particular enantiomer. This issue has already been briefly described in the literature [ 67 , 68 ]. One example is the application of liquid chromatography and mass spectrometry (LC-MS/MS) for the simultaneous determination of omeprazole, pantoprazole, lansoprazole, rabeprazole, and ilaprazole enantiomers.…”

Enantioseparation of chiral (benzylsulfinyl)benzamide sulfoxides by capillary electrophoresis using cyclodextrins as chiral selectors

“…Analyte resolution (R S value) was calculated according to (1) where t 1 and t 2 are the migration times of the first and second migrating enantiomers and W 1 and W 2 are the peak width or the respective peaks.…”

“…However, other atoms such as sulfur or phosphor in the appropriate oxidation status such as sulfonate and sulfoxide and phosphine or phosphonate, respectively, can also be stereogenic centers. Many pharmacologically active substances are chiral sulfoxides including pharmaceuticals such as proton pump inhibitors [1] or cyclooxygenase inhibitors [2] or plant secondary metabolites [3]. Furthermore, sulfoxides originate from the oxidation of sulfide groups of compounds.…”

“…Because the pharmacological activity is often attributed to one of the sulfoxide enantiomers, their separation has been of great interest. This is especially true for proton pump inhibitors which have been analyzed by HPLC, sub/supercritical fluid chromatography (SFC) or capillary electrophoresis (CE) as recently summarized [1].…”

“…Consequently, CE has been used for the separation of the enantiomers of many compounds in various analytical fields including pharmaceuticals [21][22][23][24], bioanalysis [25] food [26,27] or environmental analysis [28]. However, while the CE enantioseparations of chiral sulfoxide drugs such as proton pump inhibitors have been frequently explored [1], the resolution of the enantiomers of model sulfoxide compounds as described for HPLC above has been scarcely studied by CE. The enantioseparation of "simple" aliphatic/aromatic sulfoxides is generally challenging because these structures cannot be ionized and do not contain many groups that can interact with cyclodextrins, which are the most often applied chiral selectors in CE [29][30][31].…”