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 microg ml(-1) for benazepril hydrochloride and 6.2-25.0 microg ml(-1) for hydrochlorothiazide. The intra- and interday R.S.D. values were <1.25% (n = 5), while the relative percentage error (Er) was <0.9% (n = 5). The detection limits attained according to IUPAC definition were 0.88 and 0.58 microg 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 microg ml(-1) for benazepril hydrochloride and 18.50-42.20 microg 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 (Er < 0.99%). The detection limits were found to be 2.46 and 1.57 microg 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.

Kinetic study on the acidic hydrolysis of lorazepam by a zero-crossing first-order derivative UV-spectrophotometric technique.

A zero-crossing first-order derivative UV-spectrophotometric technique for monitoring the main degradation product, 6-chloro-4-(2-chlorophenyl)-2-quinazoline carboxaldehyde, was developed to study the acidic hydrolysis of lorazepam in hydrochloric acid solutions of 0.1 M. Due to the complete overlap of the spectral bands of the parent drug and the hydrolysis product (the range between their spectral maxima was only 3 nm), the graphical methods of derivative spectrophotometry were not efficient. The relative standard deviation of the proposed technique was less than 2.4% and the detection limit was 6.6x10(-8) M. Accelerated studies at higher temperatures have been employed that enable rapid prediction of the long-term stability of this drug. Pseudo-first order reaction kinetics was observed. Kinetic parameters, k(obs) and t(1/2), were calculated, which were similar to those estimated by an HPLC method developed in our laboratory.

Kinetic study on the degradation of prazepam in acidic aqueous solutions by high-performance liquid chromatography and fourth-order derivative ultraviolet spectrophotometry.

A reversed-phase HPLC method was developed for the kinetic investigation of the acidic hydrolysis of prazepam which was carried out in hydrochloric acid solutions of 0.01, 0.1 and 1.0 M. In addition, a fourth-order derivative method for monitoring the parent compound itself was proposed and evaluated. One intermediate was observed by HPLC, which should be formed from breakage of the azomethine linkage. Further slow hydrolysis of the amide bond led to the benzophenone product that was isolated and identified. The mechanism of hydrolysis was biphasic, showing a consecutive reaction with a reversible step. Relative standard deviation was less than 2% for HPLC and less than 5% for the derivative method. Detection limits were 1.2 x 10(-7) M for the former method and 6.7 x 10(-7)M for the latter. Accelerated studies at higher temperatures were employed. Results of HPLC and fourth-order derivative methods were statistically the same.