Optimisation and validation of a capillary electrophoresis method for the simultaneous determination of diazepam and otilonium bromide

Abstract

A simultaneous assay of diazepam and otilonium bromide in coated tablets by capillary zone electrophoresis (CZE) was developed. The influence of various parameters (voltage, temperature, buffer concentration and pH, ethanol percentage) on analysis time and on the theoretical plates of the two peaks was investigated by means of experimental design. A response surface study was carried out by means of a 27-run D-optimal matrix. The best background electrolyte was found to be 0.13 M, pH 2.9 Britton-Robinson buffer, containing 10% v/v ethanol. Other optimised parameters were voltage (30 kV) and temperature (30 degrees C). The UV detector for quantitation of otilonium bromide and diazepam was set at 280 nm and 230 nm, respectively. Procaine hydrochloride was used as internal standard and run time was less than five minutes. Validation was performed, for drug substance and drug product, according to ICH3 guidelines. For drug product the recovery for otilonium bromide and diazepam ranged from 98.3% to 101.2% and from 97.1% to 99.0%, respectively; the RSD values found for otilonium bromide and diazepam ranged from 2.4% to 3.0% and from 1.1% to 4.5%, respectively.

How experimental design can improve the validation process. Studies in pharmaceutical analysis

“…Plackett-Burman design was used for the evaluation of robustness of three capillary zone electrophoresis methods [23,24,27] and an HPLC method [25]. In all cases, the ranges employed were small deviations from the method setting that would normally occur.…”

“…As for the optimisation of method precision (repeatability), the Taguchi approach [12], the BoxMeyer approach [13], artificial neural networks [14] or experimental design methodology [15] are strategies that have been used. Further original applications of multivariate strategies to validation have dealt with evaluation of robustness [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31] and intermediate precision [21,25,26,32,33,34].…”

A review of analytical methods for the determination of four new phosphodiesterase type 5 inhibitors in biological samples and pharmaceutical preparations

“…Recently, Codevilla et al (2012) developed and validated a capillary zone electrophoresis (CZE) method for determination of lodenafil carbonate in drug products. There are some advantages to use the CZE method, such as rapid analysis, small sample and reagent consumption, high separation efficiency (Furlanetto et al, 2001;Yang et al, 2010). The results obtained from the UV-spectrophotometric method and CZE method were compared statistically with the LC method (Codevilla et al, 2011a) and the results showed no significant difference between these methods.…”

Mixture design in the optimization of a microemulsion system for the electrokinetic chromatographic determination of ketorolac and its impurities: Method development and validation

“…From the above results it clearly appears that the conditions required to optimize t are in conflict with the values needed to optimise R 1 . A simple way to resolve the problem is to use Derringer's desirability function (D) [14,15,19,29]. This function is a measure of overall quality and provides convenient means to compare several responses and to select the optimum with the most desirable properties.…”