Presence Of Hydrochlorothiazide Research Articles

Electrocatalytic oxidation and selective voltammetric detection of methyldopa in the presence of hydrochlorothiazide in real samples

The combination of methyldopa and hydrocholorothiazide are used to treat high blood pressure.The present research dealt with the synthesis and utilization of the hexagonal-shaped of ZnO nanoparticles (NPs) to develop a new, sensitive, and exclusive electrochemical sensor for detection of methyldopa. Thus, we did our examination on the methyldopa detection via cyclic voltammetry (CV) method, differential pulse voltammetry (DPV) technique, and chronoamperometry (CH) at molybdenum (VI) complex-ionic liquid–ZnO NP modified carbon paste electrode (MCILZNMCPE) in 0.1 M PBS (pH of 7.0) solution. The use of DPV showed linear dependence of methyldopa peak current at pH of 7.0 solution on their concentration ranging between 0.05 and 300.0 µM. Then, limit of detection (LOD) has been determined to be 20.0 nM for methyldopa. Ultimately, the modified electrode has been utilized for detecting methyldopa in the presence of hydrochlorothiazide by DPV.

Kinetics and Characterization of Degradation Products of Dihydralazine and Hydrochlorothiazide in Binary Mixture by HPLC-UV, LC-DAD and LC\u2013MS Methods

Dihydralazine and hydrochlorothiazide were stored at high temperature and humidity, under UV/Vis light and different pH, as individual drugs and the mixture. Then, a sensitive and selective HPLC-UV method was developed for simultaneous determination of dihydralazine and hydrochlorothiazide in presence of their degradation products. Finally, the degradation products were characterized through LC-DAD and LC–MS methods. Dihydralazine was sensitive to high temperature and humidity, UV/Vis light and pH ≥ 7. At the same time, it was resistant to acidic conditions. Hydrochlorothiazide was sensitive to high temperature and humidity, UV/Vis light and changes in pH. Its highest level of degradation was observed in 1 M HCl. Degradation of the drugs was higher when they were stressed in the mixture. In the case of dihydralazine, the percentage degradation was 5–15 times higher. What is more, dihydralazine became sensitive to acidic conditions. Hydrochlorothiazide was shown to be more sensitive to UV/Vis light and pH > 4. Degradation of dihydralazine and hydrochlorothiazide followed first-order kinetics. The quickest degradation of dihydralazine was found to be in 1 M NaOH while of hydrochlorothiazide was in 1 M HCl (individual hydrochlorothiazide) or at pH 7–10 (hydrochlorothiazide in the mixture). A number of new degradation products were detected and some of them were identified by our LC-DAD and LC–MS methods. In the stressed individual samples, (phenylmethyl)hydrazine and 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide were observed for the first time. Interactions between dihydralazine and hydrochlorothiazide in the mixture were confirmed by additional degradation products, e.g., 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1,4-trioxide.

Gallic acid, a phenolic compound isolated from Mimosa bimucronata (DC.) Kuntze leaves, induces diuresis and saluresis in rats.

Although present in the leaves of Mimosa bimucronata (DC.) and many other medicinal plants commonly used to augment urinary volume excretion, the effects of gallic acid as a diuretic agent remain to be studied. Wistar rats were orally treated with vehicle, hydrochlorothiazide, or gallic acid. The effects of gallic acid in the presence of hydrochlorothiazide, furosemide, amiloride, L-NAME, atropine, and indomethacin were also investigated. Diuretic index, pH, conductivity, and electrolyte excretion were evaluated at the end of the experiment (after 8 or 24h). Gallic acid induced diuretic and saluretic (Na+ and Cl-) effects, without interfering with K+ excretion, when orally given to female and male rats at a dose of 3mg/kg. These effects were associated with increased creatinine and conductivity values while pH was unaffected by any of the treatments. Plasma Na+, K+, and Cl- levels were not affected by any of the acute treatments. The combination with hydrochlorothiazide or furosemide was unable to intensify the effects of gallic acid when compared with the response obtained with each drug alone. On the other hand, the treatment with amiloride plus gallic acid amplified both diuresis and saluresis, besides to a marked potassium-sparing effect. Its diuretic action was significantly prevented in the presence of indomethacin, a cyclooxygenase inhibitor, but not with the pretreatments with L-NAME or atropine. Although several biological activities have already been described for gallic acid, this is the first study demonstrating its potential as a diuretic agent.

A Capillary Zone Electrophoresis Method with Multiresponse Chemometric Optimization for the Simultaneous Determination of Zofenopril Calcium and Hydrochlorothiazide in Presence of Hydrochlorothiazide Major Impurities.

In the present decade, great importance has been focused on the development of green analytical methods (GAM) as eco-friendly techniques. Minimizing the wastes, analysis time, hazardous reagents, sample size and energy are the main important principles for development of GAM. This manuscript describes a green, novel, rapid, accurate and reliable capillary zone electrophoresis method (CZE) for the simultaneous separation and determination of zofenopril calcium (ZOF) and hydrochlorothiazide (HCT) in presence of two major impurities of HCT, namely; chlorothiazide (CT) and salamide (DSA). Uncoated fused-silica capillary (50 μm i.d. × 48.5 cm and 40 cm effective length) was used. The main factors affecting the separation were the buffer concentration, pH of the buffer and applied voltage. Optimization of the experimental conditions was performed by applying response surface methodology (RSM). The experiments were designed using central composite face-centered design (CCD). The model obtained from the design described the linear, non-linear and interaction effects of factors on the responses. The optimum conditions given by the design were running buffer of sodium borate (pH 9.15; 10 mM) and 17 kV as positive mode applied voltage. Upon applying these conditions, baseline separation for the four compounds with short analysis time of 5.0 min was achieved. UV detection was performed at 225.0 nm and the capillary temperature was maintained at 25°C. The method was validated and applied for quantitative determination of the studied drugs according to the International Conference on Harmonization (ICH) guidelines. Good linearity was obtained in the range of 10.0-100.0 μg/mL for both ZOF and HCT. As for CT and DSA (HCT impurities), linearity range was 5.0-100.0 μg/mL. The proposed method was successfully applied for the analysis of these drugs in their synthetic mixtures and in their co-formulated pharmaceutical formulations.

An innovative validated spectrofluorimetric method for determination of Lisinopril in presence of hydrochlorothiazide; application to content uniformity testing

A new sensitive and discriminating spectrofluorimetric method has been developed and validated for determination of Lisinopril, one of the angiotensin converting enzyme inhibitors, in its pure bulk form and pharmaceutical tablets. The reaction of Lisinopril with ethylacetoacetate and formaldehyde in acidic buffered medium (pH3.8) has yielded a pale yellow product that exhibited a high fluorescence measured at 438nm after excitation at 350nm. All the experimental parameters affecting the formation and stability of the produced fluorophore were carefully investigated and optimized to give the maximum sensitivity. The fluorescence intensity was directly proportional to the drug concentration in the range of 0.5–4.5μg/mL with a limit of detection equal to 0.16μg/mL. The method was successfully applied in the analysis of the commercially available pharmaceutical tablets containing the single drug or its binary mixtures with Hydrochlorothiazide. Furthermore, the developed procedure was adapted for studying the content uniformity test of some dosage forms containing the cited drug.

Selective spectrofluorimetric method for determination of Lisinopril in pharmaceutical preparations and in presence of hydrochlorothiazide: Application to content uniformity testing.

A novel sensitive and cost-effective spectrofluorimetric method has been developed and validated for determination of lisinopril (an angiotensin converting enzyme inhibitor) in its pure form and pharmaceutical preparations. The method is based on the reaction of the drug with ninhydrin and phenylacetaldehyde in buffered medium (pH7.0) to form a highly fluorescent product measured at 460nm after excitation at 390nm. Different experimental parameters were optimized and calibration curve was constructed. The fluorescence-concentration relationship was linear in the range of 0.15-4.0μg mL-1 . The calculated Limit of detection (LOD) and Limit of quantitation (LOQ) were 0.04 and 0.12μg mL-1 , respectively. The method was successfully applied for the analysis of pharmaceutical preparations containing the studied drug either alone or co-formulated with hydrochlorothiazide. The obtained results were in agreement with those of the reported method in respect to accuracy and precession. Moreover, the method was applied content uniformity testing according to United States Pharmacopeia (USP) guidelines.

Complete Evaluation of Recent Smart Spectrophotometric Methods for Determination of Highly Overlapped Combinations Through Their Zero Order Profiles

In recent years, several smart spectrophotometric methods were developed for determination of highly overlapped binary mixtures by obtaining the zero order spectrum for each analyte. The validity of selected three spectrophotometric methods were tested for determination of anti-hypertensive combinations containing Hydrochlorothiazide (HCTZ). The first combination was Benazepril (BENZ) and Hydrochlorothiazide (I), the second combination was Olmesartan (OLM) and Hydrochlorothiazide (II), while the third combination was Irbesartan (IRB) and Hydrochlorothiazide (III). The first method tested was the ratio difference spectrophotometric method for determination of (I) and (II). The second method was the constant center method for determination of (I) and (II). The third method was the absorption factor (AF) for zero order and amplitude factor (P-F) for first order spectrum for determination of (III). Also, a fourth stability indicating spectrophotometric method was developed for determination of BENZ and HCTZ in presence of Benazeprilate (BENZT) which is the main degradation product of BENZ. ICH guidelines were followed for validation of the methods. The methods were compared to reported methods where no significant differences were found.

An effective and sensitive stability-indicating chromatographic approach based on HPLC for silodosin assay

A stability-indicating reversed-phase high-performance liquid chromatography (HPLC) method with a high sensitivity was developed for the determination of silodosin (SIL) in the presence of hydrochlorothiazide (HCT) as an internal standard. Chromatographic separation of SIL and IS were successfully achieved on an Agilent ZORBAX CN column with an isocratic mobile phase composed of a mixture of methanol:acetonitrile:ammonium acetate (pH 4.0; 0.015 M) (40:30:30, v/v/v) at a flow rate of 1.3 mL min−1. The drugs were quantified using a photodiode array detector set at a wavelength of 270 nm. The reversed-phase HPLC method has been validated as per International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines to determine SIL in pharmaceutical dosage form. The proposed method showed a good linearity in the concentration range of 4.0–600.0 μM with a lower detection limit of 85.0 nM under optimized conditions. The statistical performance of the fully validated HPLC method was compared to our developed sensitive spectrofluorimetric method, and the performance results of the proposed HPLC method were considerably satisfactory. The validated method was successfully applied to quantify the SIL in capsules, and the corresponding recovery value was found to be 99.5 %. The validated HPLC method may be a promising alternative analytical tool for routine analysis of SIL in pharmaceutical samples.

Quantitative Estimation of Four Sartans in Presence of Hydrochlorothiazide in Pharmaceutical Preparations by High Performance Liquid Chromatography

A simple, reliable, reproducible, economical and rapid isocratic RP-HPLC method was developed for the simultaneously separated and quantification of four angiotensin II-receptor antagonists namely Telmisartan (TELM), Losartan (LOSA), Olmesartan (OLME) and Valsartan (VALS) along with thiazide diuretic mostly Hydrochlorothiazide (HCTZ). All the above said drugs were separated by using Welchrom C18 column having internal diameter of 4.6 X 250 mm with 5 µm particle size as stationary phase with mobile phase consisting a mixture of acetonitrile and phosphate buffer (pH-3.3, 50:50 v/v). The mobile phase was pumped at a flow rate of 1 ml/min. The wave length of the UV detection was done at 238 nm. All the sartans were separated within 6 minutes. The calibration curves were linear (r2 = 0.9998) in all cases. The relative standard deviation was less than 2% and average recovery was above 99.95%. All four sartans were routinely assayed without interference. This method was statistically validated in different parameters like linearity, precision, specificity, accuracy, robustness and ruggedness. The optimized method proved to be accurate, specific and robust for the quality control of four angiotensin-II receptor blockers alone or in combination with HCTZ in bulk drug and tablet dosage forms.

Application of capillary electrophoresis-frontal analysis for comparative evaluation of the binding interaction of captopril with human serum albumin in the absence and presence of hydrochlorothiazide

The application of capillary electrophoresis-frontal analysis for comparative evaluation of the binding interaction between antihypertensive drug captopril and human serum albumin in the absence and presence of diuretic drug hydrochlorothiazide was presented in this work. At near-physiological conditions (67mM phosphate buffer, pH 7.4, I=0.17, 37°C), the individual solution of 100μM captopril and the co-binding solution with 60μM hydrochlorothiazide added were pre-equilibrated with series concentrations of HSA (10–475μM) respectively, introducing hydrodynamically into an uncoated fused silica capillary (35cm×50μm I.D. with 26.5cm effective length). The values of number of binding sites, the binding constant for captopril and hydrochlorothiazide binding to HSA were obtained, respectively. It can be found that both drugs exhibit moderate binding properties towards HSA and there does not exist significant competitive binding effects between them.

Determination of losartan potassium in the presence of hydrochlorothiazide via a combination of magnetic solid phase extraction and fluorometry techniques in urine samples

A sensitive and highly efficient method for the determination of losartan potassium (LOS) in the presence of hydrochlorothiazide (HCTZ) via a combination of magnetic solid phase extraction (MSPE) and fluorometry techniques is suggested.

Proconvulsive effect of hydrochlorothiazide in an in vitro rat seizure model.

Protective effects of diuretics, particularly of hydrochlorothiazide (HCT), for the development of epilepsy have been described in vivo. However, its mechanism of action is unknown. Extracellular field potentials were recorded from the CA1- and CA3-subfields of the hippocampus of rats. Epileptiform discharges were induced by omission of Mg2+ from the artificial cerebrospinal fluid (ACSF). HCT was added to the ACSF at a concentration of 2 mmol/l, 0.2 mmol/l or 0.02 mmol/l. Frequency, amplitude and duration of the epileptiform discharges were evaluated. Long-term potentiation (LTP) was induced with and without the presence of HCT (n=6; 2 mmol/l). In addition, rats were injected with HCT (n=4) or saline (n=2), and the brain tissue was analyzed using HPLC. Application of 0.02, 0.2, and 2 mmol/l HCT accelerated the frequency of discharges by 50%, 91%, and 100%, respectively. The amplitude of burst discharges also increased by 9%, 54%, and 300%, and the duration of epileptiform discharges increased by 10%, 30% and 120%. All parameters returned close to the basal levels after 60min washout of the substance. HCT increased the electrical evoked potentials but did not affect the LTP in hippocampal tissues. There was no evidence of HCT in the rat brain after intraperitoneal injection. Exposure of hippocampal slices to HCT enhanced epileptiform activity in a dose-dependent manner. In addition, HCT does not seem to cross the blood brain barrier in rats. Thus, the anticonvulsive effect of HCT most likely is not through direct neuronal effect.

Modern Spectrophotometric methods for quantitative determination of binary mixture of hydrochlorothiazide and amiloride hydrochloride without prior separation

Simple, accurate, sensitive and precise UV spectrophotometric methods were developed and validated for quantitative determination of binary mixture of hydrochlorothiazide (HCZ) and amiloride hydrochloride (AM) in their bulk powder and pharmaceutical dosage forms. AM was determined in presence of HCZ by direct spectrophtometry at λmax 361 nm. Three spectrophotometric methods, namely; isoabsorptive point (I), ratio subtraction (II) and ratio difference (III) were developed for the spectral resolution of HCZ when present in mixture with AM without preliminary separation. In method (I), the isoabsorptive point (Aiso) at 277.2 nm was chosen for determination of HCZ while in method (II), HCZ was determined at λmax 270.4 nm after subtraction of interference exerted by AM. In method (III), absorption spectra of HCZ were recorded, divided by suitable divisor of AM then measuring the absorption difference at 267.6 and 290.2 nm to obtain the corresponding concentrations of HCZ. The developed methods were validated according to ICH guidelines demonstrating good accuracy and precision. The results were statistically compared with those obtained by reported ratio spectra derivative spectroscopic method indicting no significant difference and ability of methods to be used for routine analysis of proposed drugs.

QUANTITATIVE DETERMINATION OF FOUR ANGIOTENSIN-II-RECEPTOR ANTAGONISTS IN PRESENCE OF HYDROCHLOROTHIAZIDE BY A GRADIENT TECHNIQUE HPLC IN THEIR PHARMACEUTICAL PREPARATIONS

Losartan potassium, Valsartan, Telmisartan, and Irbesartan are angiotensin-II-receptor antagonists (ARA II) group, which used in treatment of hypertension alone or in combination with other drugs mainly Hydrochlorothiazide. A gradient HPLC method was developed for the assay of several ARAII in presence of Hydrochlorothiazide. The method was performed by reversed phase high performance liquid chromatography using a mobile phase 0.025 M potassium dihydrogen phosphate (pH 6.0): acetonitrile = 80:20% with detection at 220 nm on an ACE C18 column (250 mm × 4.6 mm, 5 µm) at flow rate 1.5 mL/min in a gradient manner. The proposed method was validated in terms of linearity, accuracy, precision, and limits of detection and quantitation.

Computational study and multivariate optimization of hydrochlorothiazide analysis using molecularly imprinted polymer electrochemical sensor based on carbon nanotube/polypyrrole film

An electrochemical sensor was developed by modifying multi-walled carbon nanotubes-molecularly imprinted polymer onto a pencil graphite electrode (PGE). A computational approach was used to screening functional monomers and polymerization solvent for rational design of molecularly imprinted polymer (MIP). Based on computational results, pyrrole and ethanol were selected as functional monomer and polymerization solvent, respectively. The MIP film was fabricated by electropolymerization of pyrrole in the presence of hydrochlorothiazide (HCT) as template molecule after electrodepositing of carboxyl functionalized multi-walled carbon nanotubes onto the surface of pencil graphite electrode. A Plackett–Burman experimental design was used to evaluate the influence of several variables on the analytical response (current). Then, the significant parameters were optimized using a central composite design, simultaneously. Under the optimized conditions, the detection limit (3sb, n=7) was found to be 1.0×10−10M. The calibration curve showed two dynamic linear ranges including 9×10−10 to 1×10−5M and 1×10−5 to 1×10−2M with correlation coefficients (r2) of 0.9986 and 0.9921, respectively. The prepared sensor showed a suitable reproducibility (RSD % of 3.36, n=3) and regeneration capacity. The sensor showed good results for determination of HCT in serum and pharmaceutical samples.

Hydrochlorothiazide Enhances UVA‐Induced DNA Damage

The UVA is currently thought to be carcinogenic because, similar to UVB, it induces the formation of cyclobutane pyrimidine dimers (CPDs). Various drugs have been reported to cause photosensitive drug eruptions as an adverse effect. Although the precise mechanism of photosensitive drug eruption remains to be elucidated, it is generally accepted that free radicals and other reactive molecules generated via UV-irradiated drugs play important roles in the pathogenesis of photosensitive drug eruptions. The waveband of concern for photo-reactive drugs is UVA-visible light, but some extend into the UVB region. We tested whether photosensitive drugs could enhance CPD formation after UVA exposure by using isolated DNA in the presence of several reported photosensitive drugs using high-performance liquid chromatography. We found that the diuretic agent hydrochlorothiazide (HCT) significantly enhanced the production of TT dimers over a wide range of UVA. Furthermore, we investigated whether UVA plus HCT could enhance CPD production in xeroderma pigmentosum model mice defective in nucleotide excision repair. Immunofluorescence studies showed that CPD formation in the skin significantly increased after 365 nm narrow-band UVA irradiation in the presence of HCT, compared with that in wild-type mice. HCT could be used with caution because of its enhancement of UVA-induced DNA damage.

Quantitative Determination of three Angiotensin-II-receptor Antagonists in Presence of Hydrochlorothiazide by RP-HPLC in their Tablet Preparations.

Losartan potassium, Valsartan , Telmisartan and Irbesartan are angiotensin-II-receptor antagonists (ARA II) group which used in treatment of hypertension alone or in combination with other drugs mainly Hydrochlorothiazide. RP- HPLC method was developed for the assay of three angiotensin-II-receptor antagonists (ARA-IIs) in presence of Hydrochlorothiazide. The method was performed by reversed phase high performance liquid chromatography using a mobile phase which is consisted of 0.025 M potassium dihydrogen phosphate (pH 6.0): acetonitrile = 65:35% with detection at 220 nm on an ACE C18 column (250 mm × 4.6 mm, 5 μm) at flow rate 1.5 mL/min in an isocratic manner. The proposed method was validated according to ICH guidline in terms of linearity, accuracy, precision , robustness, limit of detection and limit of quantitation.

Quantitative Determination of Four Angiotensin-II-Receptor Antagonistsin Presence of Hydrochlorothiazide by a Gradient Technique HPLC in their Pharmaceutical Preparations

Losartan potassium, Valsartan , Telmisartan and Irbesartan are angiotensin-II-receptor antagonists (ARA II) group which used in treatment of hypertension alone or in combination with other drugs mainly Hydrochlorothiazide. A gradient HPLC method was developed for the assay of several ARAII in presence of Hydrochlorothiazide. The method was performed by reversed phase high performance liquid chromatography using a mobile phase 0.025 M potassium dihydrogen phosphate (pH 6.0): acetonitrile =80:20% with detection at 220 nm on an ACE C18 column (250 mm × 4.6 mm, 5 μm) at flow rate 1.5 ml/min in a gradient manner. The proposed method was validated in terms of linearity, accuracy, precision and limits of detection and quantitation.

Determination of irbesartan in the presence of hydrochlorothiazide by derivative spectrophotometry

A first-derivative spectrophotometric method for the determination of irbesartan (IRB) alone and in the presence of hydrochlorothiazide (HCT) is described. Measurements are made at the zero-crossing wavelength at 263.0 nm for IRB. The calibration graph was linear over the range 1.0–12.0 mg l −1 of IRB, detection limit was 0.15 mg l −1. HCT, in the presence of IRB was determined by direct spectrophotometric method at 317 nm. The calibration graph was linear over the range 2.0–50.0 mg l −1 of HCT, detection limit was 0.25 mg l −1. The proposed methods were successfully applied to the determinations of IRB and HCT in combined tablets.

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.