Ekram M. Hassan

Spectrophotometric and fluorimetric methods for the determination of meloxicam in dosage forms

Four simple and accurate methods are presented for the determination of meloxicam in dosage forms. These methods are based on: the direct measurements of the differential spectra at 339.9-384.7 nm (A), the 1D-values at 322-368 nm and 2D-values at 343.2-385.6 nm (B), the formation of an ion-association complex between the drug and safranin T with subsequent absorption measurement at 518 nm (C) and fluorescence measurement at 582 nm (D). All variables were studied to optimize the formation of the ion-association complex. Beers law was valid over the concentration range 2-10 microg ml(-1) (method A), 1-10 microg ml(-1) (method B), 4.0-12 microg ml(-1) (method C) and 0.4-1.2 microg ml(-1) (method D). The detection limits were 0.11, 0.07, 0.10, 0.33 and 8.74 x 10(-3) microg ml(-1) for methods A, B, C and D, respectively. The proposed methods were successfully applied to the assay of meloxicam in tablets and suppositories. The procedures were rapid, simple and suitable for quality control applications.

Development of a differential pulse voltammetric method for the determination of Silymarin/Vitamin E acetate mixture in pharmaceuticals

Differential pulse voltammetric method was developed for determination of Silymarin (SMR)/Vitamin E acetate (VEA) mixture in pharmaceuticals. SMR and VE gave well-resolved diffusion-controlled anodic peaks at +756 and +444mV, respectively (versus Ag/AgCl) in Britton-Robinson buffer at pH 2.8. The solution conditions and instrumental parameters were optimized for their quantitative determination. The linear response was obtained in the range 0.1-4.0mgL(-1) with a detection limit of 0.03mgL(-1) for SMR and 0.05-4.0mgL(-1) with a detection limit of 0.01mgL(-1)for VEA.

Bioavailability study of triamterene and xipamide using urinary pharmacokinetic data following single oral dose of each drug or their combination.

An efficient chromatographic method for the simultaneous determination of triamterene (TRI) and xipamide (XIP) in urine samples, based on high performance liquid chromatography with photodiode array detector (HPLC-DAD) has been developed. The HPLC separation was performed on a RP stainless-steel C-18 analytical column (250 mm × 4.6 mm, 5 μm) with a gradient elution system of 0.05 M phosphate buffer adjusted to pH 4.0 and methanol as the mobile phase. The method was used to determine the urinary excretion profile and to calculate different urinary pharmacokinetic parameters following oral dose of their combination compared with single oral doses of each drug and hence comparing their bioavailability. Quantitation was performed using chlorthalidone as internal standard. The calibration graphs of each drug were rectilinear in the range of 0.2-40 μg/mL urine for TRI and 0.2-15 μg/mL urine for XIP. An HPLC-DAD method was also successfully developed for the simultaneous determination of the investigated drugs in pharmaceutical preparations. The methods were validated in terms of linearity, accuracy, precision, selectivity, limits of detection and quantitation and other aspects of analytical validation.

Enhanced spectrophotometric determination of two antihyperlipidemic mixtures containing ezetimibe in pharmaceutical preparations

Two spectrophotometric methods are presented for the simultaneous determination of ezetimibe/simvastatin and ezetimibe/atorvastatin binary mixtures in combined pharmaceutical dosage forms without prior separation. The first is the derivative ratio method where the amplitudes of the first derivative of the ratio spectra ((1) DD) at 299.5 and 242.5 nm were found to be linear with ezetimibe and simvastatin concentrations in the ranges 0.5-20 µgml(-1) and 1-40 µgml(-1) , respectively, whereas the amplitudes of the first derivative of the ratio spectra ((1) DD) at 289.5 and 288 nm were selected to determine ezetimibe and atorvastatin in the concentration ranges 5-50 µgml(-1) and 1-40 µgml(-1) , respectively. The second is the H-point standard additions method; absorbances at the two pairs of wavelengths, 228 and 242 nm or 238 and 248 nm, were monitored while adding standard solutions of ezetimibe or simvastatin, respectively. For the analysis of ezetimibe/atorvastatin mixture, absorbance values at 226 and 248 nm or 212 and 272 nm were monitored while adding standard solutions of ezetimibe or atorvastatin, respectively. Moreover, differential spectrophotometry was applied for the determination of ezetimibe in the two mixtures without any interference from the co-existing drug. This was performed by measurement of the difference absorptivities (ΔA) of ezetimibe in 0.07 M 30% methanolic NaOH relative to that of an equimolar solution in 0.07 M 30% methanolic HCl at 246 nm. The described methods are simple, rapid, precise and accurate for the determination of these combinations in synthetic mixtures and dosage forms.

Liquid chromatographic determination of flunarizine dihydrochloride in the presence of its degradation product.

A simple, stability-indicating liquid chromatographic method has been developed for the assay of flunarizine dihydrochloride in the presence of its acid-induced degradation product. A Bondapak-C18 column was used with a mobile phase consisting of methanol-water (75:25, v/v) containing 0.5% w/v sodium chloride and 0.2% v/v triethanolamine adjusted to pH 6.6 with 30% hydrochloric acid at a flow rate 2 ml min-1. Quantitation was achieved with UV detection at 254 nm based on peak area or peak height ratios. The proposed method was successfully applied to the determination of the drug in laboratory-prepared mixtures in the presence of its degradation product and in capsules. Moreover, the method was utilized to investigate the kinetics of the degradation process at different temperatures and the apparent first-order rate constant, half-life and activation energy calculated.

Development and Validation of a High-Performance Thin-Layer Chromatographic Method for the Simultaneous Determination of Two Binary Mixtures Containing Ketorolac Tromethamine with Phenylephrine Hydrochloride and with Febuxostat

A validated and highly selective high-performance thin-layer chromatography (HPTLC) method was developed for the determination of ketorolac tromethamine (KTC) with phenylephrine hydrochloride (PHE) (Mixture 1) and with febuxostat (FBX) (Mixture 2) in bulk drug and in combined dosage forms. The proposed method was based on HPTLC separation of the drugs followed by densitometric measurements of their spots at 273 and 320 nm for Mixtures 1 and 2, respectively. The separation was carried out on Merck HPTLC aluminum sheets of silica gel 60 F254 using chloroform-methanol-ammonia (7:3:0.1, v/v) and (7.5:2.5:0.1, v/v) as mobile phase for KTC/PHE and KTC/FBX mixtures, respectively. Linear regression lines were obtained over the concentration ranges 0.20-0.60 and 0.60-1.95 µg band(-1)for KTC and PHE (Mixture 1), respectively, and 0.10-1.00 and 0.25-2.50 µg band(-1) for KTC and FBX (Mixture 2), respectively, with correlation coefficients higher than 0.999. The method was successfully applied to the analysis of the two drugs in their synthetic mixtures and in their dosage forms. The mean percentage recoveries were in the range of 98-102%, and the RSD did not exceed 2%. The method was validated according to ICH guidelines and showed good performances in terms of linearity, sensitivity, precision, accuracy and stability.

Colorimetric Determination of Mebeverine Hydrochloride in Tablets by Charge

AbstractThree simple, rapid and sensitive colorimetric methods for the assay of mebeverine hydrochloride are described. The first method is based on the reaction of mebeverine with iodine to give a yellow molecular charge transfer complex in chloroform with a maximum absorbance at 292nm. The other two methods depend on the formation of radical anions between mebeverine hydrochloride and tetracyanoethylene (TCNE) or 7,7,8,8-tetracyanoquinodimethane (TCNQ) in acetonitrile with absorbance maxima at 416, 840 nm, respectively. Beers law was obeyed for the proposed methods, the apparent molar absorptivities were calculated to be 1.42×105, 1.46×104 and 1.59×104 respectively. The proposed methods have been applied for the assay of mebeverine hydrochloride in commercial tablets.

A stability–indicating first–derivative spectrophotometric assay of acetazolamide and its use in dissolution and kinetic studies

A simple, rapid, stability–indicating first–derivative spectrophotometric assay procedure for the determination of the degradation products of acetazolamide is described. The dissolution and kinetics of drug degradation in aqueous buffered solutions were studied using the proposed method. Acetazolamide solution exhibited optimum stability at pH 4. The influences of temperature and sonic energy on the degradation of acetazolamide in 0–01 M NaOH solution were also studied. The results showed first–order reaction kinetics, with a degradation rate constant and degradation half–life of 31 times 10‐3 day‐1 and 8–23 days, respectively.

Spectrophotometric determination of ascorbic acid and thiamine hydrochloride in pharmaceutical products using derivative spectrophotometry

Direct spectrophotometric methods for the determination of ascorbic acid (vitamin C) and thiamine hydrochloride (vitamin B1) each in the presence of its degradation product are presented. The methods are based on the use of UV derivative spectrophotometric measurements—the first derivative at 215 nm for ascorbic acid and the second derivative at 254 nm for thiamine hydrochloride. The values obtained are linearly related to the concentration of each vitamin solution and have relative standard deviations of 0.52 and 1.07%, respectively. The mean percentage recoveries for mixtures of each vitamin with their respective degradation product were found to be 101.5 and 99.4%, respectively. Graphs of log C(%m/V)versus time for ascorbic acid solution in 3 N hydrochloric acid and for thiamine hydrochloride solution in buffer at pH 10 were straight lines with slopes of –0.1044 d–1 and –0.0207 h–1, respectively. The methods have been successfully applied to monitor the stability of the vitamins.

Assay of Glafenine and Floctafenine and Their Degradation Products in Combination

Abstract Methods for the assay of glafenine and floctafenine with their respective degradation products, glafenic acid and floctafenic acid, in combination have been described. The first derivative spectrophotometric method (D1-) and the differential derivative (first, ΔD1 second ΔD2) method have been used for the assay of the intact drugs in the presence of 4‐25% of the corresponding acids. The latter could be also determined through ion pair salt formation with basic fuchsin. That method gave highly accurate results for glafenic acid and floctafenic acid recovery even in the presence of the corresponding intact drugs constituting up to 85% of the mixture.