Hydrochlorothiazide In Pharmaceutical Dosage Form Research Articles

Resolution of overlapping spectra using chemometric manipulations of UV-spectrophotometric data for the determination of Atenolol, Losartan, and Hydrochlorothiazide in pharmaceutical dosage form

Simultaneous determination of atenolol (ATN), losartan potassium (LOS), and hydrochlorothiazide (HCZ) in presence of HCZ impurity B was conducted by chemometric approaches and radial basis function network (RBFN) using UV-spectrophotometry without preliminary separation. Three chemometric models namely, classical least-squares (CLS), principal component regression (PCR), and partial least-squares (PLS) along with RBFN were utilized using the ternary mixtures of the three drugs. The multivariate calibrations were obtained by measuring the zero-order absorbance of the mixtures from 250 to 270 nm at the interval of 0.2 nm. The models were built covering the concentration range of (4.0 to 20.0), (3.8 to 20.2), and (0.9 to 50.1) μg mL−1 for ATN, LOS, and HCZ, respectively. The regression coefficient was calculated between the actual and predicted concentrations of the 3 drugs using CLS, PCR, PLS and RBFN. The accuracy of the developed models was evaluated using the root mean square error of prediction (RMSEP) giving satisfactory results. The proposed methods were simple, accurate, precise and were applied efficiently for the quantitation of the three components in laboratory-prepared mixtures, and in dosage form showing good recovery values. In addition, the obtained results were compared statistically with each other using ANOVA test showing non-significant difference between them.

Development and Validation of Chemometric Assisted FTIR Spectroscopic Method for Simultaneous Estimation of Valsartan and Hydrochlorothiazide in Pure and Pharmaceutical Dosage Forms

Objectives: To develop a new Chemometric assisted Fourier transform infrared (FTIR) spectroscopic method for the simultaneous estimation of valsartan and hydrochlorothiazide in pharmaceutical dosage forms. Methods: The method involves the preparation of solid pellets of valsartan and hydrochlorothiazide using KBr and direct measurement using reduced path length cell. The wave numbers for quantitative estimation were selected with aid of chemometrics software and the spectra were measured in absorbance mode. Results: The infrared spectra showed different peaks with baseline correction, among which intense, clear and proportionate peaks were selected at 1600 cm-1 and 3361 cm-1 corresponding to amide (C=O) and amine (N-H) functional groups for valsartan and hydrochlorothiazide respectively for quantitative estimation were assessed using Chemometrics. Beer Lambert’s law was obeyed over the concentration range of 5-25μg/mg for valsartan and 10-50 μg/mg for hydrochlorothiazide. The method was validated according to ICH guidelines. Conclusion: The developed method was cost effective and fulfilled most validation requirements in a range of concentrations suitable for quality control of both in pure and solid dosage form. This method can be used as an alternative method for HPLC, UV or pharmacopoeial methods as quality control check in pure and marketed formulations. Key words: Chemometrics, FTIR, Hydrochlorothiazide, ICH guidelines, Method validation Valsartan.

Development of Validated Q-absorbance Ratio, Derivative Spectrophotometric and Stability indicating RP-HPLC methods for the simultaneous estimation of Losartan Potassium & Hydrochlorothiazide in Pharmaceutical Dosage Form and comparison of the results by ANOVA

Hypertension is estimated to cause 7.5 million deaths, leading to 12.8 % of the total of all deaths worldwide. In the recent years, the combination of Losartan Potassium and Hydrochlorothiazide has attained significant popularity in reducing the risk of heart diseases particularly in the patients with hypertension and ventricular hypertrophy. The literature survey revealed that there were several chromatographic and spectroscopic methods for the simultaneous estimation of the selected drugs but it was noted that there were no reported comparative studies of the developed methods. Hence the authors attempted to develop new validated Q- absorbance ratio, Derivative spectrophotometric and Stability indicating RP-HPLC methods for the simultaneous estimation of Losartan Potassium and Hydrochlorothiazide in pharmaceutical dosage form. The authors also propose to compare the results obtained by ANOVA. The two Spectrophotometric methods were carried out using an Agilent Cary 60 UV-Visible double beam Spectrophotometer. In Q-absorbance ratio method, samples were measured at two wavelengths, 230 nm (isoabsorptive point) and 225.5 nm (?max of Hydrochlorothiazide). In Derivative spectroscopy, analysis was performed by derivatizing the zero order spectrum to the corresponding second order spectrum. Stability indicating RP-HPLC method was performed using Eclipse XDB C18 column where the samples were analyzed using a mixture of Acetonitrile and Water in the ratio of 70:30 % v/v as mobile phase at a flow rate of 1 ml/min. The drugs were monitored at 230 nm. The retention times for Losartan Potassium and Hydrochlorothiazide were found to be 1.010 minutes and 1.387 minutes respectively. The proposed methods were validated as per ICH guidelines. The results obtained from the three developed methods were then compared by ANOVA which indicated that the proposed methods can successfully be used for the analysis of Losartan Potassium and Hydrochlorothiazide in bulk or in combined dosage forms.

Differential pulse voltammetric method for the individual and simultaneous determination of antihypertensive drug metoprolol and its association with hydrochlorothiazide in pharmaceutical dosage forms

The present study describes a convenient method for the individual determination of antihypertensive drug metoprolol (MTP) and its association with hydrochlorothiazide (HCTZ) using a cathodically pretreated boron-doped diamond (BDD) electrode and differential pulse voltammetry (DPV). Two very well-resolved and reproducible oxidative processes of HCTZ and MTP were found at 1.11V and 1.32V (vs Ag/AgCl (3.0molL−1 KCl)), respectively, in lactate buffer solution (pH 4.0). Under the optimum analytical experimental conditions, the voltammetric method exhibited linear response for individual determination of MTP in the concentration range 0.38–22μmolL−1, with detection limit of 0.034μmolL−1, while for a simultaneous determination of HCTZ and MTP, the concentrations range were 0.51–18.7 and 1.23–22.8μmolL−1, with detection limit of 0.376 and 0.077μmolL−1 for HCTZ and MTP, respectively. The individual and simultaneous methods were successfully applied in the determination of HCTZ and MTP content in several pharmaceutical formulations, whose accuracy was attested by good agreement of the results (paired t-test at a 95% confidence level) with those obtained using high performance liquid chromatography. In order to indicate that the method is of potential application in biological fluids adequate recovery results were obtained for the determination of HCTZ and MTP in urine samples.

Simultaneous Determination of Carvedilol and Hydrochlorothiazide in Pharmaceutical Dosage Form by Second Order Derivative UV Spectrophotometry

Derivative spectrophotometry offers a useful approach for the analysis of drugs in multi-component formulation. In this study a second order derivative spectrophotometric method is applied for the simultaneous determination of Carvedilol and Hydrochlorothiazide in tablet dosage form. The measurements were carried out at wavelengths of 292 and 272 nm for Carvedilol and Hydrochlorothiazide respectively. The method was found to be linear (r2=0.999) in the range of 5–25 μg/ml for Carvedilol in the presence of 20 μg/ml of Hydrochlorothiazide at 292 nm. The linear correlation (r2=0.999) was obtained in the range of 5–25 μg/ml for Hydrochlorothiazide in the presence of 20 μg/ml of Carvedilol at 272 nm. The method was successfully used for simultaneous determination of Carvedilol and Hydrochlorothiazide in tablet dosage form without any interference from excipients and prior separation.

Validated HPTLC technique for simultaneous estimation of candesertan celexitil and hydrochlorothiazide in pharmaceutical dosage form

Aim: Analytical HPTLC technique was developed for the simultaneous estimation of candesertan celexitil (CAN) and hydrochlorothiazide (HYD) in 2 totally different strengths of pharmaceutical dosage form. Materials and Methods: Chromatography was performed on 60F 254 TLC pre-coated aluminum plates with mobile phase of toluene: ethyl acetate: formic acid (85%) in the ratio of 6:4:1 v/v. The mean Rf values with standard deviation were found to be 0.39 ± 0.01 and 0.73 ± 0.01 for CAN and HYD, respectively. Results: The linear regression data has shown a good linear relationship over a concentration range of 200-1200 ng/spot for each drug with a correlation coefficient of 0.9999. Limit of quantification and the limit of detection establish the sensitivity of the developed technique. The stability study indicates that drugs were stable up to 72 hours. The technique was precise and relative standard deviations were found to be less than 0.05%. System suitability tests are used to verify that the resolution and repeatability of the system is adequate for the analysis. The technique was specific and selective since there is no additional peak beside with main peak. The Robustness study, recovery study and percentage of assay of the formulation were within the limit as per ICH guidelines. Conclusion: A simple, rapid, cost-effective, eco-friendly, specific, precise, sensitive and efficient analytical HPTLC technique was developed for the simultaneous estimation of candesertan celexitil (CAN) and hydrochlorothiazide (HYD) completely in 2 totally different strength of pharmaceutical marketed formulations.

HPLC and UPLC Methods for the Simultaneous Determination of Enalapril and Hydrochlorothiazide in Pharmaceutical Dosage Forms

High efficiency and less elution are the basic requirements of high-speed chromatographic separation. In this study, a new gradient reverse phase chromatographic methods were developed using HPLC and UPLC systems for simultaneous determination of enalapril maleate (ENL) and hydrochlorothiazide (HCZ) in pharmaceutical dosage forms. The chromatographic separations of ENL and HCZ were achieved on a Waters μ-Bondapak C 18, (300 × 3.9 mm, 10 μm) and Waters Acquity BEH C18 (100 × 2.1 mm, 1.7 μm) columns for HPLC within 5.30 min and UPLC within a short retention time of 1.95 min, respectively. A linear response was observed over the concentration range 0.270–399 μg mL−1 of ENL, 0.260–399 μg mL−1 of HCZ for HPLC system and 0.270–399 μg mL−1 of ENL and 0.065–249 μg mL−1 of HCZ for UPLC system. Also, limit of detection for ENL was 1.848 ng mL−1 and 31.477 ng mL−1 for HCZ, 2.804 ng mL−1 for ENL and 2.943 ng mL−1 for HCZ using HPLC and UPLC, respectively. The proposed methods were validated according to ICH guideline with respect to precision, accuracy, and linearity. Forced degradation studies were also performed for both compounds in bulk drug samples to demonstrate the specificity and stability indicating power of the HPLC method. Comparison of system performance with conventional HPLC was made with respect to analysis time, efficiency, and resolution.

Stability Indicating HPLC Method for the Determination of Hydrochlorothiazide in Pharmaceutical Dosage form

A stability indicating analytical method has been developed and validated. In this study Hydrochlorothiazide was degraded under different stress test conditions as per International Conference on Harmonization. The degraded samples were used to develop a stability-indicating high performance liquid chromatographic (HPLC) method for the Hydrochlorothiazide. The Hydrochlorothiazide was well separated from degradation products using a reversed-phase (C-18) column and a mobile phase comprising of Methanol: Buffer pH- 3.2 (60:40 v/v) and other HPLC parameters were flow rate 1 mL/min, detection wavelength 270 nm and injection volume 20 µl. The method was validated for linearity, precision, accuracy, ruggedness and robustness. Results obtained after validation study indicating that the proposed single method allowed analysis of 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 stability of the Hydrochlorothiazide in commercial pharmaceutical dosage form.

Fast gradient high performance liquid chromatography method with UV detection for simultaneous determination of seven angiotensin converting enzyme inhibitors together with hydrochlorothiazide in pharmaceutical dosage forms and spiked human plasma and urine

The development of a reversed phase liquid chromatographic method for the simultaneous determination of seven angiotensin converting enzyme (ACE) inhibitors; five drugs namely benazepril HCl (BZL), enalapril maleate (ENL), fosinopril sodium (FSP), lisinopril (LSP) and ramipril (RMP) and two metabolites captopril disulfide (CPD) and enalaprilat (ENT) together with hydrochlorothiazide (HCT) is described. The method can serve as a substitute for many published papers for the analysis of the targeted compounds with or without hydrochloothiazide in pharmaceutical formulations as well as in spiked human plasma and urine samples. The method utilizes a simple gradient procedure for the separation in a 11min run time using acetonitrile aqueous ammonia buffer (pH 9) solution and an Extend RP-C18 (25μm particle size, 4.6mm×250mm, Agilent) HPLC column. The effluent was monitored on a UV detector at 215nm. The effect of pH, solvent strength and analysis time on the peak shape and quantification were carefully studied in order to optimize the method. Adopting the proposed procedure, the analytes produce well-shaped peaks with good linear relationship over the investigated concentration ranges. The limits of detection (LOD) and limits of quantification (LOQ) from standard drug solutions lie in the range of 17–64 and 56–212ngmL−1, respectively. Correlation coefficient values (r) higher than 0.997 were obtained for all the studied drugs in spiked human plasma and urine samples. The intra-day and inter-day precision of the method was evaluated with relative standard deviation values being satisfactory for their purposed analysis. The method was validated with respect to specificity, recovery, accuracy, precision and linearity.

Development and Validation of Stability-Indicating HPTLC Method for Analysis of Amlodipine Besilate, Losartan Potassium and Hydrochlorothiazide in Pharmaceutical Dosage Form

The present work describes a stability-indicating HPTLC method for simultaneous analysis of Amlodipine besilate (AMLO), Losartan Potassium (LOS) and Hydrochlorothiazide (HCTZ) in bulk and pharmaceutical dosage form. Aluminium plate precoated with silica gel 60 F 254 was used as stationary phase. The separation was carried out using chloroform: ethyl acetate: methanol: ammonia (4: 4: 2:0.2 v/v/v/v) as mobile phase. The densitometric scanning was carried out at 232 nm. The linearity was obtained in the range 100-800 ng per band for amlodipine besilate (Correlation coefficient: 0.9954), 400-2400 ng per band for hydrochlorothiazide (Correlation coefficient: 0.9952) and 1000-8000 ng per band for losartan potassium (Correlation coefficient: 0.9947). The method was validated as per ICH guidelines. The combined dose tablet formulation was subjected to forced degradation by acid, alkali, oxidation, dry heat and exposure to ultraviolet radiations at 254 nm. The degradation products were well resolved from the pure drug with significantly different R f values.

RP-HPLC method for simultaneous estimation of bisoprolol fumarate and hydrochlorothiazide in tablet formulation

A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous determination of bisoprolol fumarate and hydrochlorothiazide in pharmaceutical dosage form. The method involves the use of easily available inexpensive laboratory reagents. The separation was achieved on an Inertsil ODS 3V (25 cm × 4.6 mm) 5 μm column with isocratic flow. The mobile phase at a flow rate of 1.0 mL min −1, consisted of 0.1 M potassium dihydrogen phosphate buffer and acetonitrile (70:30, v/v). The UV detection was carried out at 228 nm. A linear response was observed over the concentration range 2.5–50 μg mL −1 of bisoprolol fumarate and the concentration range 6.25–125 μg mL −1 of hydrochlorothiazide. Limit of detection and limit of quantitation for bisoprolol fumarate were 0.01 and 0.03 μg mL −1, respectively and for hydrochlorothiazide were 0.01 and 0.05 μg mL −1, respectively. The method was successfully validated in accordance to ICH guidelines acceptance criteria for specificity, linearity, accuracy, precision, robustness, ruggedness and system suitability. Individual drugs (bisoprolol fumarate and hydrochlorothiazide), their combinations and the tablets were exposed to thermal, photolytic, hydrolytic and oxidative stress conditions. The resultant stressed samples were analyzed by the proposed method. The method gave high resolution among the degradation products and the analytes. The peak purity of analyte peaks in the stressed samples was confirmed by photodiode array detector. The method was used for accelerated stability study on marketed and in-house formulations. The analysis concluded that the method was selective for simultaneous estimation of bisoprolol fumarate and hydrochlorothiazide and was stability-indicating.

A new RP-HPLC method for simultaneous estimation of nebivolol hydrochloride and hydrochlorthiazide in dosage forms

A new RP-HPLC method has been developed for the simultaneous estimation of nebivolol hydrochloride and hydrochlorothiazide in pharmaceutical dosage forms, using ultra violet (UV) detector. Elution was carried out using a mobile phase consisting of acetonitrile and potassium dihydrogen phosphate buffer (pH 3.2 ± 0.1) in the ratio of 50:50 v/v and s ow rate was set on 1.2 ml/min at 282 nm. The retention time for hydrochlorothiazide and nebivolol hydrochloride was found 3.57 and 6.66 mins, respectively. The method was found to be linear in the range of 8–32 μg/ml and 20–80 μg/ml for nebivolol hydrochloride and hydrochlorothiazide, respectively. In the linearity study, regression equation and coefÞ cient of correlation for nebivolol hydrochloride and hydrochlorothiazide were found to be: y = 284761x + 215452, r = 0.9995; and y = 698395+105272, r = 0.9998, respectively. Key words: HPLC, Hydrochlorthiazide, method validation, nebivolol hydrochloride.

Application of first-derivative, ratio derivative spectrophotometry, TLC-densitometry and spectrofluorimetry for the simultaneous determination of telmisartan and hydrochlorothiazide in pharmaceutical dosage forms and plasma

Four sensitive methods are described for the direct determination of telmisartan (TELM) and hydrochlorothiazide (HCT) in combined dosage forms without prior separation. The first method is a first derivative spectophotometry ( 1D) using a zero- crossing technique of measurement at 241.6 and 227.6 nm for TELM and HCT, respectively. The second method is the first derivative of ratio spectrophotometry ( 1DD) where the amplitudes were measured at 242.7 nm for TELM and 274.9 nm for HCT. The third method is based on TLC separation of the two drugs followed by the densitometric measurements of their spots at 295 and 225 nm for TELM and HCT, respectively. The separation was carried out on silica gel 60 F 254 using butanol: ammonia 25% (8:2 v/v) as mobile phase. The fourth method is spectrofluorimetric determination of TELM, depending on measuring the native fluorescence of the drug in 1 M sodium hydroxide at λ excitation 230 nm and emission at 365 nm. The proposed methods were applied successfully for the determination of the two drugs in bulk powder and in pharmaceutical formulations. The spectrofluorimetric method was utilized for the analysis of TELM in human plasma.

SPECTROPHOTOMETRIC ANALYSIS OF VALSARTAN AND HYDROCHLOROTHIAZIDE

ABSTRACT Two new methods for the simultaneous determination of valsartan and hydrochlorothiazide in pharmaceutical dosage forms have been developed. The first method, based on compensation technique is presented for the derivative spectrophotometric determination of binary mixtures with overlapping spectra. By using ratios of the derivative maxima or the derivative minimum, the exact compensation of either component in the mixture can be achieved, followed by its determination. The second method, differential derivative spectrophotometry, comprised of measurement of the difference absorptivities derivatized in the first order (ΔD 1) of a tablet extract in 0.1 N NaOH relative to that of an equimolar solution in methanol at wavelengths of 227.8 and 276.5 nm, respectively. Neither sample pre-treatment nor separation were required. These methods showed good linearity, precision, and reproducibility. The results obtained were compared with the results of reversed phase HPLC. It was found that the difference was not statistically important between these methods. The proposed methods were accurate, sensitive, precise, reproducible and could be applied directly and easily to the pharmaceutical preparations.

Simultaneous determination of benazepril hydrochloride and hydrochlorothiazide by micro-bore liquid chromatography

A micro-bore liquid chromatographic method was developed for the simultaneous determination of benazepril hydrochloride and hydrochlorothiazide in pharmaceutical dosage forms. The use of a BDS C-18 micro-bore analytical column, results in substantial reduction in solvent consumption and increased sensitivity. The mobile phase consisted of a mixture of 0.025 M sodium dihydrogen phosphate (pH 4.8) and acetonitrile (55:45, v/v), pumped at a flow rate of 0.40 ml min −1. Detection was set at 250 nm using an ultraviolet detector. Calibration graphs are linear ( r better than 0.9991, n=5), in concentration range 5.0–20.0 μg ml −1 for benazepril hydrochloride and 6.2–25.0 μg ml −1 for hydrochlorothiazide. The intra- and interday R.S.D. values were <1.25% ( n=5), while the relative percentage error ( E r) was <0.9% ( n=5). The detection limits attained according to IUPAC definition were 0.88 and 0.58 μg ml −1 for benazepril hydrochloride and hydrochlorothiazide, respectively. The method was applied in the quality control of commercial tablets and content uniformity test and proved to be suitable for rapid and reliable quality control.

Simultaneous determination of benazepril hydrochloride and hydrochlorothiazide in tablets by second-order derivative spectrophotometry

A second-order derivative spectrophotometric method for the simultaneous determination of benazepril hydrochloride and hydrochlorothiazide in pharmaceutical dosage forms is described. The determination of benazepril hydrochloride in the presence of hydrochlorothiazide was achieved by measuring the second-order derivative signals at 253.6 and 282.6 nm, while the second-order derivative signal at 282.6 nm was measured for the determination of hydrochlorothiazide. The linear dynamic ranges were 14.80–33.80 μg ml −1 for benazepril hydrochloride and 18.50–42.20 μg ml −1 for hydrochlorothiazide, the correlation coefficient for the calibration graphs were better than 0.9998, n=5, the precision (%RSD) was better than 1.43% and the accuracy was satisfactory ( E r<0.99%). The detection limits were found to be 2.46 and 1.57 μg ml −1 for benazepril hydrochloride and hydrochlorothiazide, respectively. The method was applied in the quality control of commercial tablets and proved to be suitable for rapid and reliable quality control.