Method Development and Validation for the Determination of Potential Impurities Present in Olmesartan Medoxomil and Hydrochlorothiazide in Fixed Dose Combination Drug Product by Using Reverse Phase – Ultra-Performance Liquid Chromatography Coupled with Diode-Array Detector

Abstract

A simple, sensitive, and reproducible ultra-performance liquid chromatography (UPLC) method for the determination of nine known potential impurities present in Olmesartan medoxomil and Hydrochlorothiazide tablets in fixed dose combination drug product was developed. Chromatographic separation was achieved between impurities at satisfactory level using Acquity UPLC HSS T3, 100 mm length × 2.1 mm id with 1.8 µm particle size column. Gradient elution mode was kept using mobile phase A as 0.1% orthophosphoric acid buffer adjusted the pH 2.5 and acetonitrile as mobile phase B. Flow rate was kept at 0.5 mL min⁻¹ with a monitoring wavelength of 225 nm. The method is fast and uses less consumption of solvents with shorter run time of 9 min. This can enable the separation of all known potential impurities of two active compounds in a rapid, precise, sensitive, cost, and time effective manner. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, solution stability, and robustness. The method is fast and is suitable for high-throughput analysis of the drug facilitating the processing of large-number batch samples.

Keywords:

• forced degradation
• hydrochlorothiazide
• Olmesartan medoxomil
• RP-UPLC
• stability indicating