Maha A. Hegazy

Novel spectrophotometric methods for simultaneous determination of timolol and dorzolamide in their binary mixture

Two smart and novel spectrophotometric methods namely; absorbance subtraction (AS) and amplitude modulation (AM) were developed and validated for the determination of a binary mixture of timolol maleate (TIM) and dorzolamide hydrochloride (DOR) in presence of benzalkonium chloride without prior separation, using unified regression equation. Additionally, simple, specific, accurate and precise spectrophotometric methods manipulating ratio spectra were developed and validated for simultaneous determination of the binary mixture namely; simultaneous ratio subtraction (SRS), ratio difference (RD), ratio subtraction (RS) coupled with extended ratio subtraction (EXRS), constant multiplication method (CM) and mean centering of ratio spectra (MCR). The proposed spectrophotometric procedures do not require any separation steps. Accuracy, precision and linearity ranges of the proposed methods were determined and the specificity was assessed by analyzing synthetic mixtures of both drugs. They were applied to their pharmaceutical formulation and the results obtained were statistically compared to that of a reported spectrophotometric method. The statistical comparison showed that there is no significant difference between the proposed methods and the reported one regarding both accuracy and precision.

Simultaneous determination of some cholesterol-lowering drugs in their binary mixture by novel spectrophotometric methods

Four simple, specific, accurate and precise spectrophotometric methods manipulating ratio spectra were developed and validated for simultaneous determination of simvastatin (SM) and ezetimibe (EZ) namely; extended ratio subtraction (EXRSM), simultaneous ratio subtraction (SRSM), ratio difference (RDSM) and absorption factor (AFM). The proposed spectrophotometric procedures do not require any preliminary separation step. The accuracy, precision and linearity ranges of the proposed methods were determined, and the methods were validated and the specificity was assessed by analyzing synthetic mixtures containing the cited drugs. The four methods were applied for the determination of the cited drugs in tablets and the obtained results were statistically compared with each other and with those of a reported HPLC method. The comparison showed that there is no significant difference between the proposed methods and the reported method regarding both accuracy and precision.

Quantitative determination of oxybutynin hydrochloride by spectrophotometry, chemometry and HPTLC in presence of its degradation product and additives in different pharmaceutical dosage forms

Simple, accurate, sensitive and validated UV spectrophotometric, chemometric and HPTLC-densitometric methods were developed for determination of oxybutynin hydrochloride (OX) in presence of its degradation product and additives in its pharmaceutical formulations. Method A is the first derivative of ratio spectra (DD(1)) which allows the determination of OX in presence of its degradate in pure form and tablets by measuring the peaks amplitude at 216 nm. Method B and C are principal component regression (PCR) and partial least-squares (PLS) for determination of OX in presence of its degradate in pure form, tablets and syrup. While, the developed high performance thin layer chromatography HPTLC-densitometric method was based on the separation of OX from its degradation product, methylparaben and propylparaben followed by densitometric measurement at 220 nm which allows the determination of OX in pure form, tablets and syrup. The separation was achieved using HPTLC silica gel F(254) plates and chloroform:methanol:ammonia solution:triethylamine (100:3:0.5:0.2, v/v/v/v) as the developing system. The accuracy, precision and linearity ranges of the developed methods were determined. The results obtained were statistically compared with each other and to that of a reported HPLC method, and there was no significant difference between the proposed methods and the reported method regarding both accuracy and precision.

Simultaneous determination of metformin hydrochloride and pioglitazone hydrochloride in binary mixture and in their ternary mixture with pioglitazone acid degradate using spectrophotometric and chemometric methods

In this work two well known oral hypoglycemic drugs that are administered in combination for patients with type-II diabetes were simultaneously determined. Several spectrophotometric methods were developed and validated for the determination of metformin hydrochloride (MET), pioglitazone hydrochloride (PIO) and pioglitazone acid degradate (PIO Deg). Derivative, ratio derivative, isosbestic and chemometric-assisted spectrophotometric methods were developed. The first derivative (D(1)) method was used for the determination of MET in the range of 5-30 microg x mL(-1) and PIO in the range of 10-90 microg x mL(-1) by measuring the peak amplitude at 247 nm and 280 nm, respectively. The concentration of PIO was calculated directly at 268 nm. The first derivative of ratio spectra (DD(1)) method used the peak amplitudes at 238 nm and 248.6 nm for the determination of MET in the range of 5-30 microg x mL(-1). In the isosbestic point method (ISO), the total mixture concentration was calculated by measuring the absorbance at 254.6 nm. Classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS-2) were used for the quantitative determination of MET, PIO and PIO Deg. The methods developed have the advantage of simultaneous determination of the cited components without any pre-treatment. Resolution and quantitative determination of PIO degradate with a minimum concentration of 3 microg x mL(-1) in drug samples was done. The proposed methods were successfully used to determine each drug and the acid degradate in a laboratory-prepared mixture and pharmaceutical preparations. The results were statistically compared using one-way analysis of variance (ANOVA). The methods developed were satisfactorily applied to the analysis of the two drugs in pharmaceutical formulations.

DIFFERENT SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION OF CIMETIDINE, RANITIDINE HYDROCHLORIDE, AND FAMOTIDINE

ABSTRACT In this work three different spectrophotometric methods were established for the determination of cimetidine (I), ranitidine hydrochloride (II) and famotidine (III) The first one is a colorimetric method, it was applied for the determination of the three drugs by using sodium nitroprusside as a color reagent to produce a red colored complexes. In this method, the zero order spectrum 0D was used for the determination of drug (III) at λ=500 nm while the first derivative spectra 1D were used for the determination of drug (I) and (II) at their corresponding wave lengths 523 and 510 nm and Δ λ=4 nm. The method can be considered as a stability indicating method for the determination of the three drugs in the presence of their induced hydrogen peroxide oxidative degradates. Beers law was obeyed in the concentration range of 25–150 µg·mL−1 for (I) and 50–500 µg·mL−1 for (II) and (III) with mean percentage recoveries of 100.27±0.697, 99.79±0.465 and 99.15±0.687, respectively. The second method is a simple colorimetric method, it was applied for the determination of drug (III). Where, 3-Methyl-2-benzo-thiazolinone hydrazone (MBTH) was used as a color reagent. It reacts with the drug to produce a bluish violet color, having two maxima at 536 and 620 nm. The percentage recoveries were 99.73±1.048 and 99.94±0.887, respectively within the concentration range of 20–120 µg·mL−1. The third one is a spectrophotometric method via a complex formation reaction by using cobalt II. A colorless complex was developed having λ max at 319 nm with a ratio of 1:1 and a stability constant logarithm of 5.49. The percentage recovery was 99.84±0.858 within a concentration range of 10–60 µg·mL−1. The statistical comparison with the BP official methods[1] and the assay validation for the three proposed methods has been applied. The results obtained showed that they could be used for the determination of the three drugs in pure and dosage forms.

Validated green high-performance liquid chromatographic methods for the determination of coformulated pharmaceuticals: A comparison with reported conventional methods

The introduction of sustainable development concepts to analytical laboratories has recently gained interest, however, most conventional high-performance liquid chromatography methods do not consider either the effect of the used chemicals or the amount of produced waste on the environment. The aim of this work was to prove that conventional methods can be replaced by greener ones with the same analytical parameters. The suggested methods were designed so that they neither use nor produce harmful chemicals and produce minimum waste to be used in routine analysis without harming the environment. This was achieved by using green mobile phases and short run times. Four mixtures were chosen as models for this study; clidinium bromide/chlordiazepoxide hydrochloride, phenobarbitone/pipenzolate bromide, mebeverine hydrochloride/sulpiride, and chlorphenoxamine hydrochloride/caffeine/8-chlorotheophylline either in their bulk powder or in their dosage forms. The methods were validated with respect to linearity, precision, accuracy, system suitability, and robustness. The developed methods were compared to the reported conventional high-performance liquid chromatography methods regarding their greenness profile. The suggested methods were found to be greener and more time- and solvent-saving than the reported ones; hence they can be used for routine analysis of the studied mixtures without harming the environment.

Novel spectrophotometric methods for simultaneous determination of Amlodipine, Valsartan and Hydrochlorothiazide in their ternary mixture

This work represents a comparative study of two smart spectrophotometric techniques namely; successive resolution and progressive resolution for the simultaneous determination of ternary mixtures of Amlodipine (AML), Hydrochlorothiazide (HCT) and Valsartan (VAL) without prior separation steps. These techniques consist of several consecutive steps utilizing zero and/or ratio and/or derivative spectra. By applying successive spectrum subtraction coupled with constant multiplication method, the proposed drugs were obtained in their zero order absorption spectra and determined at their maxima 237.6 nm, 270.5 nm and 250 nm for AML, HCT and VAL, respectively; while by applying successive derivative subtraction they were obtained in their first derivative spectra and determined at P230.8-246, P261.4-278.2, P233.7-246.8 for AML, HCT and VAL respectively. While in the progressive resolution, the concentrations of the components were determined progressively from the same zero order absorption spectrum using absorbance subtraction coupled with absorptivity factor methods or from the same ratio spectrum using only one divisor via amplitude modulation method can be used for the determination of ternary mixtures using only one divisor where the concentrations of the components are determined progressively. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulation containing the cited drugs. Moreover comparative study between spectrum addition technique as a novel enrichment technique and a well established one namely spiking technique was adopted for the analysis of pharmaceutical formulations containing low concentration of AML. The methods were validated as per ICH guidelines where accuracy, precision and specificity were found to be within their acceptable limits. The results obtained from the proposed methods were statistically compared with the reported one where no significant difference was observed.

Comparative study of novel versus conventional two-wavelength spectrophotometric methods for analysis of spectrally overlapping binary mixture

Smart spectrophotometric methods have been applied and validated for the simultaneous determination of a binary mixture of chloramphenicol (CPL) and prednisolone acetate (PA) without preliminary separation. Two novel methods have been developed; the first method depends upon advanced absorbance subtraction (AAS), while the other method relies on advanced amplitude modulation (AAM); in addition to the well established dual wavelength (DW), ratio difference (RD) and constant center coupled with spectrum subtraction (CC-SS) methods. Accuracy, precision and linearity ranges of these methods were determined. Moreover, selectivity was assessed by analyzing synthetic mixtures of both drugs. The proposed methods were successfully applied to the assay of drugs in their pharmaceutical formulations. No interference was observed from common additives and the validity of the methods was tested. The obtained results have been statistically compared to that of official spectrophotometric methods to give a conclusion that there is no significant difference between the proposed methods and the official ones with respect to accuracy and precision.

Novel spectrophotometric determination of chloramphenicol and dexamethasone in the presence of non labeled interfering substances using univariate methods and multivariate regression model updating

Smart and novel spectrophotometric and chemometric methods have been developed and validated for the simultaneous determination of a binary mixture of chloramphenicol (CPL) and dexamethasone sodium phosphate (DSP) in presence of interfering substances without prior separation. The first method depends upon derivative subtraction coupled with constant multiplication. The second one is ratio difference method at optimum wavelengths which were selected after applying derivative transformation method via multiplying by a decoding spectrum in order to cancel the contribution of non labeled interfering substances. The third method relies on partial least squares with regression model updating. They are so simple that they do not require any preliminary separation steps. Accuracy, precision and linearity ranges of these methods were determined. Moreover, specificity was assessed by analyzing synthetic mixtures of both drugs. The proposed methods were successfully applied for analysis of both drugs in their pharmaceutical formulation. The obtained results have been statistically compared to that of an official spectrophotometric method to give a conclusion that there is no significant difference between the proposed methods and the official ones with respect to accuracy and precision.

Validated spectrophotometric methods for simultaneous determination of Omeprazole, Tinidazole and Doxycycline in their ternary mixture

A comparative study of smart spectrophotometric techniques for the simultaneous determination of Omeprazole (OMP), Tinidazole (TIN) and Doxycycline (DOX) without prior separation steps is developed. These techniques consist of several consecutive steps utilizing zero/or ratio/or derivative spectra. The proposed techniques adopt nine simple different methods, namely direct spectrophotometry, dual wavelength, first derivative-zero crossing, amplitude factor, spectrum subtraction, ratio subtraction, derivative ratio-zero crossing, constant center, and successive derivative ratio method. The calibration graphs are linear over the concentration range of 1-20 μg/mL, 5-40 μg/mL and 2-30 μg/mL for OMP, TIN and DOX, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and successfully applied to commercial pharmaceutical preparation. The methods that are validated according to the ICH guidelines, accuracy, precision, and repeatability, were found to be within the acceptable limits.