Two specific, sensitive, and precise stability indicating chromatographic methods have been developed, optimized, and validated for Hydrochlorothiazide (HCT) and Spironolactone (SPR) determination in their mixtures and in presence of their impurities and degradation products. The first method was based on thin layer chromatographic (TLC) combined with densitometric determination of the separated spots. The separation was achieved using silica gel 60 F(254) TLC plates and ethyl acetate-chloroform-formic acid-triethyl amine (7:3:0.1:0.1, by volume) as a developing system. Good correlations were obtained between the integrated peak area of the studied drugs and their corresponding concentrations in different ranges. The second method was based on the high-performance liquid chromatography with ultraviolet detection, by which the proposed components were separated on a reversed phase C(18) analytical column using gradient elution system with deionized water-acetonitrile (97:3, v/v) for 8 min. Then acetonitrile was successively increased to 35% in the next 2 min, and kept constant in the following 10 min, finally 3% acetonitrile was regained again to stabilize the chromatographic system. The flow rate was maintained at 2 mL/min and the detection wavelength was at 230 nm. Linear regressions were obtained in the range of 4.0-50 μg/mL and 5.0-50 μg/mL for both HCT and SPR, respectively. Different parameters affecting the suggested methods were optimized for maximum separation of the cited components. System suitability parameters of the two developed methods were also tested. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of HCT and SPR in their commercial tablets. Both methods were also statistically compared to each other and to the reported method with no significant difference in performance.

No abstract

No abstract

Hydrochlorothiazide (HCT) and spironolactone (SPR) are mostly co-formulated in antihypertensive formulations. Several methods have been developed and validated for their determination; these methods include spectrophotometric and chemometric-assisted spectrophotometric methods. The developed spectrophotometric methods were isosbestic point (ISO) and ratio subtraction (RS) methods. The absorbance values at 232.4 (lambda(iso1)) and 257.6 nm (lambda(iso2)) were used for determination of the total mixture concentration, while HCT could be directly determined at 317.2 nm (lambda(max)) and by subtraction SPR concentration could be obtained. Also SPR concentration could be calculated by RS method using the absorbance at 243.8 nm (lambda(max)). A wavelength selection method based on genetic algorithm (GAs) was developed and compared to the conventional partial least squares method (PLS). In this method, several parameters were adjusted and the optimum parameter settings were determined using experimental design. The developed chemometric methods were successfully applied for the determination of the HCT and SPR, as well as for determination of their impurities and degradation products. The proposed methods were successfully applied for determination of HCT and SPR in commercial tablets and they were statistically compared to each other and to the reported method. No significant difference was found, providing their accuracy and precision.

Three polyvinylchloride (PVC) membrane sensors for the determination of moexipril hydrochloride were prepared and characterized. The sensors are based on the use of the ion association complexes of moexipril cation with either ammonium reineckate (sensor 1) or tetraphenyl borate (sensor 2) or phosphotungistic acid (sensor 3) counter anions as ion exchange sites in the PVC matrix. The performance characteristics of these sensors were evaluated according to IUPAC recommendations, which reveal a fast, stable and linear response for moexipril over the concentration range of 10 -6 to 10 -2 M for the three sensors with cationic slopes of 29.1, 30.1 and 30.2 mV per concentration decade for the three sensors, respectively. The direct potentiometric determination of moexipril hydrochloride using the proposed sensors gave recoveries % of 99.64 ± 0.34, 99.34 ± 0.56 and 99.68 ± 0.42 for the three sensors, respectively. The sensors were used for determination of moexipril hydrochloride in pharmaceutical formulations and in plasma. Validation of the method shows suitability of the proposed sensors for use in quality control assessment of moexipril hydrochloride. The obtained results were in a good agreement with those obtained using the reported spectrophotometric method.