Adel M. Michael

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.

A Rapid and Sensitive HPLC Assay of Some Concomitant Anti-Migraine Drugs

This work describes a simple and sensitive method for simultaneous determination of zolmitriptan, naproxen and propranolol in their dosage forms using HPLC. The drugs were separated isocratically on a Zorbax C8 (4.6 × 250 mm with 5 µm particle size) column using a mobile phase composed of 20 mM phosphate citrate buffer [0.1% TEA (pH 3.1)]:methanol:THF (5:3:2, by volumes). The detection was accomplished fluorometrically setting the excitation wavelength at 280 nm and emission wavelength at 360 nm. The method was validated over a linearity range of 100-900 ng/mL for zolmitriptan, 50-300 ng/mL for naproxen and 100-800 ng/mL for propranolol. The assay was successfully applied to the determination of the studied drugs in pharmaceutical dosage forms without interference from tablet excipients with high specificity. The method can be applied successfully in the future for the pharmacokinetic study of these drugs in the human plasma with high accuracy especially that LOQs of zolmitriptan and propranolol in the proposed method cover their Cmax.

Simultaneous Determination of Sumatriptan and Naproxen in Dosage Forms and Human Plasma Using LC/MS

This work describes a simple and sensitive method for the concurrent determination of sumatriptan (SUM) and naproxen (NAP) in dosage forms and human plasma using LC/MS and internal standardization. The drugs were separated isocratically on a C 18 column using a binary mobile phase composed of water and acetonitrile at 0.05 % acetic acid. The method was validated over a linearity range of 10-900 ng/mL and 0.1-10 g/mL for SUM and NAP, respectively. The LOQ for SUM and NAP were 10 and 100 ng/mL, respectively. The proposed method was successfully used for the determination of SUM and NAP in plasma after a double liquid liquid extraction (LLE). The assay was successfully applied to the determination of both drugs in pharmaceutical dosage forms without interference from tablet excipients. Results obtained by the proposed method were statistically compared to those of a reported method, and no significant difference was observed

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.

Comparative Study of Multivariate and Univariate Determination of Zolmitriptan in the Presence of its Degradation products

Abstract This work describes comparative study of multivariate chemometric and univariate spectrophotometric determination of zolmitriptan (ZLM ) in the presence of its alkaline and oxidative degradation products. Both methods show high sensitivity and the same linearity range (1-6 µg/mL) while the chemometric method has the advantage of higher accuracy, higher specificity and better regression parameters. The study describes complete stability study on zolmitriptan and structure elucidation of the formed degradation products. The spectrophotometric method based on successive spectrophotometric resolution pattern namely; successive ratio subtraction (SRS) method using both degradation products as divisors successively followed by direct spectrophometric measurement of zolmitriptan at 222 nm while the chemometric method used PLS and PCR models. The proposed methods were successfully applied for the determination of zolmitriptan in pure powder as well as in its pharmaceutical formulation. Statistical comparison showed no significant difference between the developed methods and the reference method.