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In this work, enantiomeric separation of a drug combination of two chiral drugs, namely, atenolol and chlorthalidone, is described. Prior investigation of the effect of different variables on the resolution of the enantiomers' peaks and the total run time represented by the retention time of the last eluted peak was conducted using face-centered composite design. Twenty-two experiments were carried out by varying the chiral stationary phase type as a categorical factor and mobile phase composition including the percentage of ethanol and percentage of diethylamine as continuous factors. According to the optimization process, a mobile phase consisting of hexane:ethanol:DEA:TFA (60:40:0.2:0.1%, v/v/v/v) pumped at flow rate 1 ml min -1 onto Lux-Cellulose 2 stationary phase was applied for the chiral separation and quantification of the drug combination at 230 nm. Application of the developed method to the pharmaceutical formulation of this combination was successfully performed, and satisfactory percentage of recoveries was obtained. The method was also fully validated following International Conference on Harmonization (ICH) guidelines. This method could be of high value and relevance for application in quality control laboratories., (© 2021 Wiley Periodicals LLC.)

Capillary zone electrophoresis methods for the simultaneous determination of the beta-blocker drugs, atenolol, chlorthalidone and amiloride, in pharmaceutical formulations have been developed. The influences of several factors (buffer pH, concentration, applied voltage, capillary temperature and injection time) were studied. Using phenobarbital as internal standard, the analytes were all separated in less than 4 min. The separation was carried out in normal polarity mode at 25 degrees C, 25 kV and using hydrodynamic injection (10 s). The separation was effected in an uncoated fused-silica capillary (75 mum i.d. x 52 cm) and a background electrolyte of 25 mm H(3)PO(4) adjusted with 1 m NaOH solution (pH 9.0) and detection at 198 nm. The method was validated with respect to linearity, limit of detection and quantification, accuracy, precision and selectivity. Calibration curves were linear over the range 1-250 microg/mL for atenolol and chlorthalidone and from 2.5-250 microg/mL for amiloride. The relative standard deviations of intra- and inter-day migration times and corrected peak areas were less than 6.0%. The method showed good precision and accuracy and was successfully applied to the simultaneous determination of atenolol, chlorthalidone and amiloride in various pharmaceutical tablets formulations., (2010 John Wiley & Sons, Ltd.)

A high-performance liquid chromatographic method was developed for the simultaneous determination of 2 ternary mixtures containing amiloride hydrochloride, atenolol, hydrochlorothiazide, and chlorthalidone used in hypertension therapy. The use of cyanopropyl column results in satisfactory separation of both mixtures. The mobile phase consisted of 10 mM KH2PO4 buffer (pH 4.5) and methanol in a ratio of (75 + 25% v/v), at a flow rate of 1 mL/min. UV detector was operated at 275 nm. Calibration graphs were linear in the concentration ranges of 2-10, 20-200, 10-100, and 5-50 microg/mL for amiloride hydrochloride, atenolol, hydrochlorothiazide, and chlorthalidone, respectively. Intraday and interday precision values (relative standard deviation) were <1.13 for mixture I (amiloride hydrochloride, atenolol, chlorthalidone), and <0.93 for mixture II (amiloride hydrochloride, atenolol, hydrochlorothiazide). The method was successfully applied for the determination of the 2 combinations in laboratory-prepared mixtures and commercial pharmaceutical formulation with high accuracy and precision. Statistical comparison of the results with those of the published methods showed excellent agreement and indicates no significant difference between them.

A high-performance liquid chromatographic method was optimized and validated for the determination of atenolol and chlorthalidone (CT) in human breast milk. The milk samples were extracted and purified using ACN and phosphoric acid for precipitation of proteins followed by removal of ACN and milk fats by extraction with methylene chloride. The samples were applied, after an extraction procedure, to a cyanide column using a mobile phase consisting of ACN/water (35:65 v/v) and buffered at pH 4.0 with flow rate of 1.0 mL/min. Quantitation was achieved with UV detection at 225 nm using guaifenesin as the internal standard. The effectiveness of protein precipitation and clean up procedure were investigated. The method was validated over the range of 0.3-20 microg/mL for atenolol and 0.25-5 microg/mL for CT.

A simple multivariate calibration method for analysis of two types of hypotensive mixture is described. The mixtures are composed of chlorthalidone with atenolol or chlorthalidone with both amiloride hydrochloride and atenolol. The components of the mixtures result in substantial spectral overlap-between 87.5 and 91.0%. Resolution of the mixtures under investigation has been accomplished mainly by using CLS and PCR methods. The components in each mixture have been simultaneously determined in three commercial dosage forms with high accuracy and without interference from commonly encountered excipients and additives. Good recoveries were obtained with both synthetic mixtures and commercial tablets. The results obtained were compared with those from pharmacopeial methods and found to be in good agreement. The results obtained from CLS and PCR were also compared with those obtained from a 1D spectrophotometric method.

Three methods are presented for the simultaneous determination of atenolol (AT), amiloride hydrochloride (AM) and chlorthalidone (CD). The high performance liquid chromatographic (HPLC) method depends on the separation of each drug on a reversed phase, RP (18) column. Elution was carried out with a mobile phase consisting of acetonitrile -5mM heptansulphonic acid sodium salt (20:80, v/v, pH 4.4). Quantitation was achieved with UV detection at 274 nm based on peak area. The other two-chemometric-assisted spectrophotometric methods applied were principal component regression (PCR) and partial least squares (PLS-1). These approaches were successfully applied to quantify each drug in the mixture using the information included in the absorption spectra of appropriate solutions in the range 240-290 nm with the intervals Deltalambda=0.2 nm. The three methods were successfully applied to a pharmaceutical formulation (tablets), and the results were compared with each other.

Resolution of binary mixtures of atenolol (ATE) and chlorthalidone (CTD) with minimum sample pre-treatment and without analyte separation has been successfully achieved, using a new and rapid method based on partial least squares (PLS1) analysis of UV spectral data. The simultaneous determination of both analytes was possible by PLS1 processing of sample absorbances between 255 and 300 nm for ATE and evaluation of absorbances in the 253-268 nm region for CTD. The mean recoveries for synthetic samples were 100.3 +/- 1.0% and 100.7 +/- 0.7% for ATE and CTD, respectively. Application of the proposed method to two commercial tablet preparations in the content uniformity test showed them to contain 103.5 +/- 0.8% and 104.9 +/- 1.8% ATE respectively, as well as 103.4 +/- 1.2% and 104.5 +/- 2.2% CTD. Use of this method also allowed the elaboration of dissolution profiles of the drugs in two commercial combined formulation products, through the simultaneous determination of both drugs during the dissolution test. At the dissolution time of 45 min specified by USP XXIV, both pharmaceutical formulations complied with the test.