Method For Determination Of Hydrochlorothiazide Research Articles

The use of liquid chromatography method for quantitative determination of active substances in Enalapril-H tablets

The aim. Combination therapy is used to treat hypertension. Strengthening the action of the ACE inhibitor enalapril is carried out in combination with the thiazide diuretic hydrochlorothiazide. On the pharmaceutical market, such combined preparations are presented by different manufacturers in various concentrations of the active ingredients of enalapril maleate and hydrochlorothiazide. Development of methods for the quantitative determination of active substances in combined drugs by liquid chromatography is topical.
 Materials and methods. Shimadzu Nexera X2 LC-30AD liquid chromatograph equipped with DAD SPD-M20A diode array detector, SIL-30AC autosampler and CTO-20AC column thermostat; analytical balance - UniBloc AUW120D; pH meter - Knick type 911pH; chromatographic column ACE C18, size 250 mm × 4.6 mm, packed with octadecylsilyl silica gel for chromatography with a particle size of 5 μm.
 Results. Based on the results of the work, a method for the quantitative determination of enalapril and hydrochlorothiazide in the presence of HPLC was proposed. The obtained validation characteristics indicate that the method for the quantitative determination of hydrochlorothiazide in Enalapril-H tablets corresponds to the following parameters: correctness, precision, linearity ( =0.70 ≤ max =1.60, d=0.22 ≤ maxd = 0.51, a=0.71 max a=2.60, r = 0.9997 min r=0.9981). In the quantitative determination of enalapril maleate in combined tablets, it was found that correctness, precision, linearity are performed ( =1.21 ≤ max =1.60, d=0.24 ≤ max d=0.51, a=1.35 max a=2.60, r = 0.9991 min r= 0.9981).
 Conclusions. The method of quantitative chromatographic determination of enalapril maleate and hydrochlorothiazide in an antihypertensive combination drug has been improved. The proposed parameters of the chromatographic separation of the mixture in comparison with the initial ones contribute to a decrease in the costs of monitoring, a decrease in the volume of harmful emissions and cause an extension of the life of the chromatographic column

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

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.

Development and Validation of RP-HPLC Method for Determination of Hydrochlorothiazide, Amiloride Hydrochloride and Related Impurities in Bulk and Pharmaceutical Dosage Forms

Hydrochlorothiazide (HCZ) and Amiloride hydrochloride (AMH) are generally co-formulated in antihypertensive formulations. Different analytical methods have been developed for their simultaneous determination in their binary mixtures but none of them analyzed both drugs in the presence of related impurities of HCZ; Salamide (DSA) and Chlorothiazide (CTZ). Accordingly; a simple, sensitive and highly selective RP-HPLC method was developed for their simultaneous determination in pure form and pharmaceutical formulations. Chromatographic separation was carried out within 10 min using an ODS-C18 column (250×4.6 mm, 5 µm) using 0.05 MKH2PO4 : acetonitrile: triethylamine (90: 10: 0.3 by volume, pH 3.6) as mobile phase, flow rate 1.5 mL min−1 with UV detection at 260 nm.Calibration curves were builtin the range of 1-50, 1-20, 1-12 and 1-20 µg mL-1 for HCZ, AMH, DSA and CTZ, respectively. HCZ and AMH were successfully analyzed in their pure and pharmaceutical form. The results obtained were statistically compared to those obtained by the reported method with no significant difference, therefore the proposed method can be applied in routine quality control analysis of the drug products.

Biomimetic Sensor for Detection of Hydrochlorothiazide Employing Amperometric Detection and Chemometrics for Application in Doping in Sports

This work describes a simple and cost-effective method for quantitative determination of hydrochlorothiazide using biomimetic sensor based on a carbon paste modified with hemin (biomimetic catalyst of the P450 enzyme). The sensor was evaluated using cyclic voltammetry and amperometry for its electrochemical characterization and quantification, respectively. Amperometric analyses were carried out at 800 mV vs. Ag/AgCl (KClsat), using a 0.1 mol L−1 phosphate buffer solution at pH 8.5 as the support electrolyte. Optimization of the experimental parameters was performed using a multivariate methodology. The proposed method was successfully applied to the analysis of hydrochlorothiazide in spiked urine and pharmaceutical formulations, demonstrating that it is a reliable, feasible and efficient alternative method for the detection of hydrochlorothiazide in doping and can also be used for the quality control method.

Phosphorescence detection of hydrochlorothiazide using Mn-doped ZnS quantum dots

The room temperature phosphorescence (RTP) of quantum dots (QDs) offers many advantages compared with fluorescence, such as a longer emission lifetime, wider gap between excitation and emission spectra and minimal interference. Hence, the RTP properties of QDs and their potential for phosphorescence detection have drawn more and more attention. In this paper, N-acetyl-L-cysteine (NAC)-capped Mn-doped ZnS QDs were synthesized by a hydrothermal method. The QDs displayed a strong phosphorescence emission peak at 590 nm upon excitation at 315 nm. Because their RTP was efficiently quenched by hydrochlorothiazide (HCT), a novel RTP method for determination of HCT was developed. The results showed that under the optimized conditions, the changes of RTP intensity showed a good linear relationship with the concentration of HCT in the range of 2.5 to 95 μM, with a limit of detection of 1.25 μM and relative standard deviation of 0.44%. The related theories preliminarily demonstrated the dynamic quenching mechanism. In addition, this method was successfully applied to the analysis of practical samples. The recovery of spiked solutions ranged from 94–104%.

Validated Chromatographic Methods for Determination of Hydrochlorothiazide and Spironolactone in Pharmaceutical Formulation in Presence of Impurities and Degradants

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.

Application of h-point standard addition method for simultaneous spectrophotometric determination of hydrochlorothiazide and propranolol

The applicability of H-point standard addition method (HPSAM) to resolving overlapping spectra corresponding to the hydrochlorothiazide and propranolol was verified. The results show that the HPSAM is suitable for the simultaneous determination of hydrochlorothiazide and propranolol in aqueous media. The results of applying the HPSAM showed that the two drugs could be determined simultaneously with the concentration ratios hydrochlorothiazide:propranolol varying from 1:20 to 10:1 in a mixed sample. The proposed method has been successfully applied to the simultaneous determination of hydrochlorothiazide in the presence of propranolol in some synthetic samples. Moreover, the applicability of the method was demonstrated by their determination in some biological fluids.

Determination of hydrochlorothiazide in human plasma by liquid chromatography/tandem mass spectrometry

In this study, a fast and sensitive liquid chromatography/tandem mass spectrometry method for determination of hydrochlorothiazide in human plasma was developed and validated. The analyte and irbesartan, used as the internal standard, were precipitated and extracted from plasma using methanol. Analysis was performed on a Phenomenex Kromasil C 8 column with water and methanol (27:73, v/v) as the mobile phase. Linearity was assessed from 0.78 to 200 ng/mL in plasma. The analytical method proved to be applicable in a pharmacokinetic study after oral administration of 12 mg hydrochlorothiazide tablets to 20 healthy volunteers.

PLS and first derivative of ratio spectra methods for determination of hydrochlorothiazide and propranolol hydrochloride in tablets

Two new analytical methods have been developed as convenient and useful alternatives for simultaneous determination of hydrochlorothiazide (HCT) and propranolol hydrochloride (PRO) in pharmaceutical formulations. The methods are based on the first derivative of ratio spectra (DRS) and on partial least squares (PLS) analysis of the ultraviolet absorption spectra of the samples in the 250-350-nm region. The methods were calibrated between 8.7 and 16.0 mg L(-1) for HCT and between 14.0 and 51.5 mg L(-1) for PRO. An asymmetric full-factorial design and wavelength selection (277-294 nm for HCT and 297-319 for PRO) were used for the PLS method and signal intensities at 276 and 322 nm were used in the DRS method for HCT and PRO, respectively. Performance characteristics of the analytical methods were evaluated by use of validation samples and both methods showed to be accurate and precise, furnishing near quantitative analyte recoveries (100.4 and 99.3% for HCT and PRO by use of PLS) and relative standard deviations below 2%. For PLS the lower limits of quantification were 0.37 and 0.66 mg L(-1) for HCT and PRO, respectively, whereas for DRS they were 1.15 and 3.05 mg L(-1) for HCT and PRO, respectively. The methods were used for quantification of HCT and PRO in synthetic mixtures and in two commercial tablet preparations containing different proportions of the analytes. The results of the drug content assay and the tablet dissolution test were in statistical agreement (p < 0.05) with those furnished by the official procedures of the USP 29. Preparation of dissolution profiles of the combined tablet formulations was also performed with the aid of the proposed methods. The methods are easy to apply, use relatively simple equipment, require minimum sample pre-treatment, enable high sample throughput, and generate less solvent waste than other procedures.

Anti-beer Evaluation of Hydrochlorothiazide and Losartan by UV Derivative Spectrophotometry

An UV derivative method for the simultaneous determination of Hydrochlorothiazide (HCT) and Losartan (LST) in the commercial forms was developed. The fourth derivative spectrum from the alcoholic solution was used. HCT can be determined by a specific signal at 330–340 nm, while LST uses the signal around 280–290 nm, common to both products. Into the concentration range of HCT (10.8–500)10−3 mg mL−1 and of LST (20–2400)10−3 mg mL−1, for their mixture in the ratio 1:4, two intervals were identified, one for lower values, for which the absorbance grows with concentration, and one for higher values, in which the absorbance of the solution diminishes as concentration increases. The second behaviour seems to be due to intramolecular reactions of the drugs. For both the intervals, linear regressions were obtained by correlating the spectra signals with the drug concentrations. The best results were obtained by employing the regression equations from the downward section.

Simple method for determination of hydrochlorothiazide in human urine by high performance liquid chromatography utilizing narrowbore chromatography

A simple high performance liquid chromatographic (HPLC) method utilizing narrowbore chromatography was developed for the determination of hydrochlorothiazide in human urine. A mobile phase of 0.1% aqueous acetic acid—acetonitrile (93:7, v/v) pH 3 was used with a C18 analytical column and ultraviolet detection (UV). The method demonstrated linearity from 2 to 50 μg ml −1 using 50 μl of urine with a detection limit of 1 μg ml −1. The method was utilized in a study evaluating if racial differences are present in the pharmacokinetic and pharmacodynamic effects of hydrochlorothiazide.