Yasmin M. Fayez

Simultaneous determination of mebeverine hydrochloride and chlordiazepoxide in their binary mixture using novel univariate spectrophotometric methods via different manipulation pathways.

Smart, sensitive, simple and accurate spectrophotometric methods were developed and validated for the quantitative determination of a binary mixture of mebeverine hydrochloride (MVH) and chlordiazepoxide (CDZ) without prior separation steps via different manipulating pathways. These pathways were applied either on zero order absorption spectra namely, absorbance subtraction (AS) or based on the recovered zero order absorption spectra via a decoding technique namely, derivative transformation (DT) or via ratio spectra namely, ratio subtraction (RS) coupled with extended ratio subtraction (EXRS), spectrum subtraction (SS), constant multiplication (CM) and constant value (CV) methods. The manipulation steps applied on the ratio spectra are namely, ratio difference (RD) and amplitude modulation (AM) methods or applying a derivative to these ratio spectra namely, derivative ratio (DD(1)) or second derivative (D(2)). Finally, the pathway based on the ratio spectra of derivative spectra is namely, derivative subtraction (DS). The specificity of the developed methods was investigated by analyzing the laboratory mixtures and was successfully applied for their combined dosage form. The proposed methods were validated according to ICH guidelines. These methods exhibited linearity in the range of 2-28μg/mL for mebeverine hydrochloride and 1-12μg/mL for chlordiazepoxide. The obtained results were statistically compared with those of the official methods using Student t-test, F-test, and one way ANOVA, showing no significant difference with respect to accuracy and precision.

Micellar Electrokinetic Chromatography (MEKC) with Multiresponse Chemometric Optimization for the Determination of Hydrochlorothiazide and Coformulated Antihypertensives in the Presence of Hydrochlorothiazide Major Impurity

In this work, micellar electrokinetic chromatographic method was developed and optimized for the determination of hydrochlorothiazide (HCT) in the presence of irbesartan (IRB), bisoprolol (BISO) and HCT main impurity. Four factors affecting the separation-sodium dodecyl sulphate (SDS) concentration, buffer concentration, temperature and voltage-were studied. Optimization studies were performed with the aid of a central composite design with six central points. The optimal separation conditions were obtained by applying Derringers desirability function, and the conditions were borate buffer 17 mM (pH = 9), SDS 5.2 mM, temperature 25°C and voltage 12 kV. HCT, IRB and BISO were successfully determined in their pure form and pharmaceutical formulations with separation in <8 min. Calibration curves (R > 0.999) were prepared and complete method validation was performed according to ICH guidelines. The results obtained were statistically compared with that of the official methods.

Novel Stability-Indicating Chemometric-Assisted Spectrophotometric Methods for the Determination of Chlordiazepoxide and Clidinium Bromide in the Presence of Clidinium Bromide’s Alkali-Induced Degradation Product

Two simple and accurate chemometric-assisted spectrophotometric models were developed and validated for the simultaneous determination of chlordiazepoxide (CDZ) and clidinium bromide (CDB) in the presence of an alkali-induced degradation product of CDB in their pure and pharmaceutical formulation. Resolution was accomplished by using two multivariate calibration models, including principal component regression (PCR) and partial least-squares (PLS), applied to the UV spectra of the mixtures. Great improvement in the predictive abilities of these multivariate calibrations was observed. A calibration set was constructed and the best model used to predict the concentrations of the studied drugs. CDZ and CDB were analyzed with mean accuracies of 99.84 ± 1.41 and 99.81 ± 0.89% for CDZ and 99.56 ± 1.43 and 99.44 ± 1.41% for CDB using PLS and PCR models, respectively. The proposed models were validated and applied for the analysis of a commercial formulation and laboratory-prepared mixtures. The developed models were statistically compared with those of the official and reported methods with no significant differences observed. The models can be used for the routine analysis of both drugs in QC laboratories.