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

摘要

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 ) or Neb (mixture ) 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 at 215nm using acetonitrile:0.1% triethylamine pH=2 (12:88 v/v) as mobile phase at flow rate 1.0mL/min using Promosil C-18 (150mmx4.6mm i.d.; 5 mu m) column. While mixture separation was performed at 220nm using BDS Hypersil C-18 (250mmx4.6mm i.d.; 5 mu m) column with mobile phase of acetonitrile:phosphate buffer pH=3 (15:85 v/v) at flow rate 1.0mL/min. The responses were linear over concentration ranges 2.0-100 mu g/mL (r=0.9997) and 1.0-100 mu g/mL (r=0.9998) with mean recoveries 100.16% and 100.43% of Lab and HCTZ, respectively meanwhile 5.0-100 mu g/mL (r=0.9997) and 2.0-100 mu g/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.