Enantiomeric Determination of Omeprazole and Esomeprazole by a Developed and Validated Chiral HPLC Method and Stability Studies by Microthermal Analysis

Abstract

A rapid, accurate, precise, stability indicating and enantioselective chiral HPLC method was
developed and validated for the quantitative (S)- and (R)- omeprazole in omeprazole formulations along with
determination of enantiomeric purity of (S)- omeprazole in esomeprazole formulations according to the guidelines of
the United States of Pharmacopeia (USP) and International Conference on Harmonization (ICH). The
chromatographic separation was achieved with n-hexane/ 2-propanol/ acetic acid/ triethylamine (100 : 20 : 0.2 : 0.1,
v/v) at a flow rate of 1.2 ml/min on Chiralcel OD-H and detected at 300 nm. The method showed good linearity,
high sensitivity with detection limit (LOD) of 0.71 and 1.16 μg/ml and quantitation limit (LOQ) of 2.16 and 3.51
μg/ml for (S)- and (R)- omeprazole, respectively. The average percentage of recovery was found to be 100.85% to
101.36% for (S)- and 99.81% to 101.62% for (R)- omeprazole. The average percentage of relative standard deviation
(% RSD) for intra- and inter- day precision were found to be 0.05% and 0.19% for (S)- and 0.03% and 0.13% for
(R)- omeprazole, respectively. Stability study was performed under stress conditions. Microthermal analysis of
omeprazole was also performed by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and
scanning electron microscopy (SEM) to assess the physical and chemical behavior of the drug. The method was
successfully applied to the quantitation of (S)- and (R)- omeprazole for omeprazole and as well as determination of
(S)- omeprazole purity for esomeprazole formulations.