ICH guidance in practice: Validated stability-indicating HPLC method for simultaneous determination of Olmesartan medoximil and Hydrochlorothiazide in combination drug products

Abstract

Olmesartan and hydrochlorothiazide were degraded together under different stress test conditions
prescribed by International Conference on Harmonization. The samples so generated were used to
develop a stability-indicating high performance liquid chromatographic (HPLC) method for the two
drugs. The drugs were well separated from degradation products using a reversed-phase (C-18)
column and a mobile phase comprising of acetonitrile: phosphate buffer (pH 3.0), which was delivered
initially in the ratio of 15:85 (v/v) for 6 min, then changed to 30:70 (v/v) for next 20 min, and finally
equilibrated back to 15:85 (v/v) from 20 to 25 min. Other HPLC parameters were: flow rate, 1 mL
min-1; detection wavelengths, 258 nm for olmesartan and 224 nm for hydrochlorothiazide and
injection volume, 20 μL. The method was validated for selectivity, linearity, precision, accuracy, and
specificity. Results were obtained, indicating that the proposed single method allowed selective
analysis of both olmesartan and hydrochlorothiazide, in the presence of their degradation products
formed under a variety of stress conditions. The developed procedure was also applicable to the
determination of instability of the drugs in commercial products.