Suzy M. Sabry

Study of stability of methotrexate in acidic solution Spectrofluorimetric determination of methotrexate in pharmaceutical preparations through acid-catalyzed degradation reaction

Study of the degradation reaction of methotrexate (MTX) in acidic solution was carried out. Optimization of the experimental parameters of MTX acid hydrolysis was investigated. Spectrofluorimetric method for determination of MTX through measurement of its acid-degradation product, 4-amino-4-deoxy-10-methylpteroic acid (AMP), was developed. Stability of the standard solution of MTX prepared in sulfuric acid was discussed in the view of accelerated stability analysis. Two other comparative spectroflourimetric methods based on measuring the fluorescence intensities from either a condensation reaction with acetylacetone-formaldehyde (Hantzsch reaction) or a reaction with fluorescamine were also described. Beers law validation, accuracy, precision, limits of detection, limits of quantification, and other aspects of analytical merit are presented in the text. The proposed methods were successfully applied for the analysis of MTX in pure drug and tablets dosage form. The sensitivity of the developed methods was favorable, so it was possible to be adopted for determination of MTX in plasma samples for routine use in high-dose MTX therapy.

Adsorptive stripping voltammetric assay of phenazopyridine hydrochloride in biological fluids and pharmaceutical preparations

A sensitive method for the measurement of phenazopyridine hydrochloride (PAP) by differential pulse polarography (DPP) based on adsorptive stripping technique, using a hanging mercury drop electrode (HMDE) is described. The voltammetric peak is obtained at -0.760 V, which corresponds to the reduction of the azo group in Britton-Robinson buffer. The redox behaviour is reversible. Optimum conditions were found to be: accumulation potential -50 mV (vs. Ag/AgCl), accumulation time 60 s, scan rate 5 mV s(-1), pulse amplitude -100 mV and supporting electrolyte Britton-Robinson buffer (0.04 M, pH=11). The relative standard deviation (at 20 ng ml(-1) level) was +/-0.6% for six measurements. The calculated detection limit was 0.0299 ng ml(-1) with a 60-s accumulation time. The applicability of such a method was evaluated through the assay of PAP in human plasma and urine samples after a simple extraction procedure and in pharmaceutical preparation. The mean recovery was 97+/-2 (100 ng ml(-1) plasma).

Application of H-point standard additions method to spectrophotometric and spectrofluorimetric determinations of glafenine and glafenic acid in mixtures

H-point standard additions method (HPSAM), based on spectrophotometric and spectrofluorimetric measurements, was proposed for simultaneous determination of glafenine (G) and glafenic acid (GA). A study of the absorption spectra of G and GA in various pH media has been carried out. Reasonably resolved UV-absorption spectra were obtained with a solution adjusted at pH 4.5 with citric acid-phosphate buffer. Additionally, the fluorescence properties in aqueous micellar systems of anionic, cationic and non-ionic surfactants were investigated. Well resolved fluorescence spectra were established in aqueous Triton X-100 solution at pH 7.8 (citric acid-phosphate buffer). As a comparative method, UV-derivative spectrophotometry (based on zero-crossing technique) was suggested. First-derivative value at 352 nm ((1)D(352)) and second-derivative value at 366 nm ((2)D(366)) were selected for the quantification of G and GA, respectively. The relative standard deviations of the proposed methods approximate 2%. The proposed methods were evaluated through the analysis of commercial tablets. The results were accurate and precise.

Adsorptive stripping voltammetric behaviour of azomethine group in pyrimidine-containing drugs.

The stripping voltammetric behaviour of buspirone hydrochloride (BUS) and piribedil (PIR), as models of pyrimidine-containing compounds, was studied using a hanging mercury drop electrode (HMDE). A sensitive adsorptive stripping voltammetric method for determination of such drugs is described. The voltammetric peaks were obtained at -1.23 and -1.22 V for BUS and PIR. respectively, which correspond to the reduction of the azomethine group of pyrimidine ring in Britton-Robinson buffer (pH 7). Factors such as pH of supporting electrolyte, accumulation potential and time and instrumental parameters were optimized. Calibration plots and regression data validation, accuracy, precision, limits of detection, limits of quantification, and other aspects of analytical merit are presented. The applicability of the method was evaluated through determination of BUS and PIR in tablet dosage forms. A preliminary study of the analysis of plasma samples, spiked with the investigated drug, after a simple extraction procedure is described.

Spectrophotometric Determination of Bisacodyl and Piribedil

ABSTRACT Simple spectrophotometric methods are described for the assay of bisacodyl (BIS) and piribedil (PIR) based on charge‐transfer and ion‐pair complexation reactions. The first method is based on the reaction of the cited drugs with p‐chloranilic acid (p‐CA) in acetonitrile. The purple colored chromogen formed shows maximum absorbance at 518 nm. The second method is concerned with the reaction of the investigated drugs with picric acid (PA) and four sulphonphthalein acid dyes, namely; bromocresol green (BCG), bromocresol purple (BCP), bromophenol blue (BPB) and thymol blue (TB). The yellow ion‐pair complexes formed show absorption spectra with maxima within the range from 400 to 415 nm. The stoichiometric ratio was found to be 1:1, for all complexation reactions examined, as calculated by the continuous variations method. Beers law validation, accuracy, precision, limits of detection, limits of quantification, and other aspects of analytical merit are presented in the text. The proposed methods were applied for the determination of the analytes in their pure forms and in pharmaceutical preparations. The results were in good agreement with those obtained by the official and reported methods.

Voltammetric, spectrofluorimetric and spectrophotometric methods to determine flufenamic acid

Simple, rapid and sensitive voltammetric, spectrofluorimetric and spectrophotometric methods for determination of flufenamic acid (FF) in bulk powder and capsule dosage form are presented. The methods are based on the cyclisation reaction of FF with concentrated sulphuric acid to produce the corresponding acridone derivative. The voltammetric method is based on the adsorptive stripping differential pulse (DP) technique. The acridone derivative is determined over the concentration range of 8-60 ng ml(-1) using adsorptive preconcentration at the hanging mercury drop electrode (HMDE). The lower detection limit was found to be 1.02 ng ml(-1). The fluorimetric and spectrophotometric methods are based on the measurement of the fluorescence intensity at 450 nm (lambda(ex) = 400 nm)and peak-to-peak measurements of the first- (D1) and second-derivative (D2) curves, respectively. Beers law is obeyed over the concentration ranges of 2-20 ng ml(-1) and 0.2-8.0 microg ml(-1) for the fluorimetric and spectrophotometric measurements, respectively. The three methods were proved to be accurate and reproducible as indicated by a relative standard deviation of <2%.

Polarographic and Voltammetric Assays of Sulfonamides as α‐Oxo‐γ‐Butyrolactone Arylhydrazones

Abstract 2‐Acetylbutyrolactone was characterized as a novel reagent of analytical potential in polarographic and voltammetric analyses. It forms α‐oxo‐γ‐butyrolactone arylhydrazones through Japp‐Klingemann coupling reaction with primary arylamines. α‐Oxo‐γ‐butyrolactone arylhydrazones possess an electro‐active site (azomethine center) that displays a cathodic activity at the mercury electrode. The protonated azomethine center of α‐oxo‐γ‐butyrolactone arylhydrazones is reduced by 2e/2H+ reaction to the hydrazo form. The differential pulse polarographic behavior of α‐oxo‐γ‐butyrolactone arylhydrazones was investigated in aqueous media ranging from pH 2 to 10.5. In aqueous acidic solution, α‐oxo‐γ‐butyrolactone arylhydrazones were shown to adsorb on a hanging mercury drop electrode and to be amenable to determination by adsorptive stripping voltammetry. Procedures for applying the polarographic and voltammetric methods to determination of sulfadiazine and sulfamethoxazole in pharmaceutical preparations have been developed. An analogous study on sulfas‐azo derivatives of ethyl acetoacetate was also considered. Furthermore, the differential pulse voltammetric method was adopted for determination of sulfamethoxazole in spiked plasma and urine samples. The recoveries turned out to be satisfactory, showing relative standard deviations from 2.4 to 4.6%.

Sensitive spectrofluorimetric and spectrophotometric methods for the determination of thonzylamine hydrochloride in pharmaceutical preparations based on coupling with dimethylbarbituric acid in presence of dicyclohexylcarbodiimide

Two sensitive and selective spectrophotometric and spectrofluoimetric procedures were developed for the determination of thonzylamine hydrochloride (THAH) in tablets and nasal drops. The methods are based on König reaction which resulted in an orange-yellow fluorescent product. The orange-yellow product of the interaction between the dicyclohexylcarbodiimide (DCC), THAH and dimethylbarbituric acid (DMBA) showed an absorption maximum at 492 nm, a first-derivative signal at 494 nm and a fluorescence emission peak at 518 nm (lambda(ex)=492 nm). The orange-yellow color was found to be stable for at least 2 h. The reaction conditions were studied and optimized. The reaction obeys Beers law over the ranges 8-20 and 0.2-2.0 microg ml(-1) for the derivative spectrophotometric and fluorimetric measurements, respectively. The detection limits were found to be 0.29 and 0.018 microg ml(-1) for the spectrophotometric and fluorimetric measurements, respectively. The proposed methods were applied to the analysis of pharmaceutical formulations containing THAH, either alone or in combination with naphazoline nitrate.

Reversed phase-liquid chromatography of primary and secondary aliphatic amines after derivatization combined with electrochemical detection☆

Abstract An analytical procedure has been developed for the determination of primary and secondary aliphatic amines by liquid chromatography with electrochemical detection (LC-ECD). Aliphatic amines, such as propylamine (PA), butylamine (BA), 2-pentylamine (2-PA), dimethylamine (DMA), diethylamine (DEA) and dipropylamine (DPA) react readily with salicylic acid chloride (SAC) to produce electroactive amide derivatives with good chemical stability. The isocratic elution pattern of synthetic mixtures of the investigated amines on a reversed-phase column is shown. Hydrodynamic voltammograms of standard compounds are presented. The detection limits monitored with an EC detector are compared with those of an UV detector. The method was sensitive enough to detect the derivatives in the picomol range. The method was also applied for the determination of amines in plasma and urine using 2-PA and DPA as model substances. Following a solid phase extraction and derivatization, the compounds could be detected in the lower ng range/ml biological material.

Enhanced Spectrophotometry of Sulfonamides with Novel 2‐Acetylbutyrolactone Derivatives

Abstract 2‐Acetylbutyrolactone (ABL) has been characterized as a novel coupling reagent for the spectrophotometric analysis of primary arylamines. 2‐Acetylbutyrolactone is a cyclic β‐keto ester that forms colored α‐oxo‐γ‐butyrolactone arylhydrazones with primary arylamines through the Japp‐Klingemann reaction. The arylhydrazones can be measured spectrophotometrically in alkaline (A532) and acidic solutions (1D349). A similar study on ethyl acetoacetate (EAA), as a coupling carbanion, was carried out. Ethyl acetoacetate is the acyclic β‐keto ester analog of ABL that forms colored azo derivatives with primary arylamines. The azo derivatives can be measured spectrophotometrically in alkaline solution (A416). Four model sulfa drugs namely, sulfadiazine (SD), sulfamethoxazole (SMX), sulfamoxole (SMO), and sulfametrole (SMR), were evaluated throughout the work. The chemistry and the pathway of the reactions of the two β‐keto esters (ABL and EAA) were discussed. Beers law validation, accuracy, precision, limits of detection, and limits of quantification are presented in the text. The applicability of ABL and EAA was assessed through the analysis of the model drugs in pharmaceutical preparations.