Stability-indicating methods for determination of hydrochlorothiazide in combination with some antihypertensive drugs in the presence of its main impurities

Abstract

Hydrochlorothiazide (HCTZ) is potent diuretic that used alone or in combination with other antihypertensive drugs such as labetalol hydrochloride (Lab) or nebivolol hydrochloride (Neb) to control moderate to severe hypertension. As there is no published method for simultaneous determination of HCTZ and Lab (mixture Ι) or Neb (mixture ΙΙ) in pharmaceutical formulations in presence of HCTZ-related impurities, it was important to develop validated stability-indicating HPLC methods for analysis of these mixtures in quality control laboratories. These methods based on gradient RP-HPLC separation of mixture Ι at 215 nm using acetonitrile:0.1% triethylamine pH = 2 (12:88 v/v) as mobile phase at flow rate 1.0 mL/min using Promosil C18 (150 mm × 4.6 mm i.d.; 5 µm) column. While mixture ΙΙ separation was performed at 220 nm using BDS Hypersil C18 (250 mm × 4.6 mm i.d.; 5 µm) column with mobile phase of acetonitrile:phosphate buffer pH = 3 (15:85 v/v) at flow rate 1.0 mL/min. The responses were linear over concentration ranges 2.0–100 µg/mL (r = 0.9997) and 1.0–100 µg/mL (r = 0.9998) with mean recoveries 100.16% and 100.43% of Lab and HCTZ, respectively meanwhile 5.0–100 µg/mL (r = 0.9997) and 2.0–100 µg/mL (r = 0.9996) with mean recoveries 99.99% and 100.63% of Neb and HCTZ, respectively. Methods were validated according to ICH guidelines; the results were statistically compared with the company methods and there was no significant difference. The proposed methods have the advantages of being stability-indicating and time saving with low solvent consumption which favors their usage in quality control routine analysis of selected mixtures in their pharmaceutical formulations.