Reversed‐Phase Analytical Method for Enantioselective Analysis of Ormeloxifene Hydrochloride: Application to Bulk Drug and Quality Control Analysis

Abstract

ABSTRACTThe article reports simple, rapid, and novel enantioselective reversed‐phase high‐performance liquid chromatography (RP‐HPLC) for separation of (−)‐(3R, 4R)‐ormeloxifene hydrochloride (d‐ORM) and (+)‐(3S, 4S)‐ormeloxifene hydrochloride (l‐ORM) (ORM, centchroman) using chiral stationary phase (Chiral‐AGP, Chiracel OJ‐RH, and ChiraDEX HR). The best enantiomeric separation was obtained on the ChiraDEX HR (α = 0.89, Rs = 1.9) column with a gradient mode elution using a combination of ammonium acetate (10 mM, pH 4.0) and methanol as a mobile phase. The flow rate and column oven temperature were 0.7 mL/min and 30°C, respectively. The detection limits (λmax 280 nm) for d‐ORM and l‐ORM were 0.170 and 0.169 µg/mL, whereas quantification limits were 0.516 and 0.512 µg/mL. The method was validated according to the International Council on Harmonization (ICH) regulatory Guidelines Q2 (R1) in terms of its accuracy, precision, sensitivity, linearity, specificity, robustness, and solution stability. The designed analytical method could be extended as a quality control tool for pharmaceutical quality assessments as well as isomeric quantification of ORM in industrial bulk manufacturing.