Chiral Separation of Tenatoprazole and Several Related Benzimidazoles by Normal Phase LC Using Amylose-Based Stationary Phase

Abstract

Simple and efficient analytical LC methods using amylose-based stationary phase Chiralpak AS-H were developed for direct enantioseparation of tenatoprazole and several related benzimidazoles. The chromatographic experiments were performed in the normal phase mode with n-hexane–ethanol–triethylamine (TEA) as mobile phase. The effects of the mobile phase additive, concentration of organic modifiers and column temperature were studied for the enantioseparation. The thermodynamic parameters were also calculated from the van’t Hoff plots. It was found that the enantioseparations were all enthalpy driven. The enantiomers of all compounds were resolved (R s > 3.3) within 14 min using n-hexane–ethanol–TEA (20:80:0.1%, v/v/v) as mobile phase with a flow rate of 0.4 mL min−1 at 40 °C. The optimized method was validated for determination of the enantiomers of tenatoprazole in terms of linearity, precision and accuracy according to ICH guidelines and applied to the assay of tenantoprazole bulk drugs. The proposed method was shown to be accurate and suitable for the quantitative determination of tenatoprazole enantiomers.