Gamal A. Saleh

Analysis of cephalosporin antibiotics

A comprehensive review with 276 references for the analysis of members of an important class of drugs, cephalosporin antibiotics, is presented. The review covers most of the methods described for the analysis of these drugs in pure forms, in different pharmaceutical dosage forms and in biological fluids.

Use of charge-transfer complexation in the spectrophotometric analysis of certain cephalosporins.

Three simple, rapid and sensitive spectrophotometric procedures were developed for the analysis of cephapirin sodium (1), cefazoline sodium (2), cephalexin monohydrate (3), cefadroxil monohydrate (4), cefotaxime sodium (5), cefoperazone sodium (6) and ceftazidime pentahydrate (7) in pure form as well as in their pharmaceutical formulations. The methods are based on the reaction of these drugs as n-electron donors with the sigma-acceptor iodine, and the pi-acceptors: 2,3-dichloro-5,6-dicyano-p-benzo-quinone (DDQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ). Depending on the solvent polarity, different coloured charge-transfer complexes and radicals were developed. Different variables and parameters affecting the reactions were studied and optimized. The obtained charge-transfer complexes were measured at 364 nm for iodine (in 1,2-dichloroethane), 460 nm for DDQ (in methanol) and 843 nm for TCNQ (in acetonitrile). Ultraviolet-visible, infrared and (1)H-nuclear magnetic resonance techniques were used to study the formed complexes. Due to the rapid development of colours at ambient temperature, the obtained results were used on thin-layer chromatograms for the detection of the investigated drugs. Beers plots were obeyed in a general concentration range of 6-50, 40-300 and 4-24 mug ml(-1) with iodine, DDQ and TCNQ, respectively, with correlation coefficients not less than 0.9989. The proposed procedures could be applied successfully to the determination of the investigated drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 96.47 (+/-1.14) to 98.72 (+/-1.02) in the iodine method, 96.35 (+/-1.62) to 98.51 (+/-1.30) in the DDQ method, and 95.98 (+/-0.78) to 98.40 (+/-0.87) in the TCNQ method. The association constants and standard free energy changes using Benesi-Hildebrand plots were studied. The binding of cephalosporins to proteins in relation to their molar absorptivities was studied.

Spectrofluorometric determination of certain quinolone antibacterials using metal chelation

Simple, rapid, reliable, and sensitive spectrofluorometric methods were developed for the determination of eight quinolone antibacterials namely ciprofloxacin, norfloxacin, lomefloxacin, difloxacin, amifloxacin, pefloxacin, ofloxacin, and nalidixic acid. The methods depend on the chelation of each of the studied drugs with zirconium, molybdenum, vanadium or tungsten to produce fluorescent chelates. Different factors affecting the relative fluorescence intensity of the resulting chelates were studied and optimised. At the optimum reaction conditions, the drug-metal chelates showed excitation maxima ranging from 274 to 295 nm and emission maxima ranging from 409 to 495 nm. The chelates were found to be stable at room temperature for 2 days and show good stability upon increasing temperature to 50 degrees C for about 1 h. Rectilinear calibration graphs were obtained in the range of 10-60 ng ml(-1) for each of the investigated drugs and the limits of detection and quantitation ranged from 1.214 to 2.046 and from 4.047 to 6.819 ng ml(-1), respectively. The molar ratios of the formed chelates were determined by Jobs method and their association constants were also calculated. The developed methods were applied successfully for the determination of the studied drugs in their pharmaceutical dosage forms with a good precision and accuracy compared to official and reported methods as revealed by t- and F-tests. They were also applied for the determination of studied drugs in spiked urine and plasma samples.

Selective spectrophotometric determination of phenolic β-lactam antibiotics

Abstract Two simple and selective spectrophotometric methods were developed for the quantitative determination of cefoperazone sodium, cefadroxil monohydrate, cefprozil anhydrous and amoxicillin trihydrate in pure forms as well as in their pharmaceutical formulations. The methods are based on the selective oxidation of these drugs with either Ce (IV) or Fe (III) in acid medium to give an intense yellow coloured product ( λ max =397 nm). The reaction conditions were studied and optimized. Beers plots were obeyed in a general concentration range of 5–30 μg ml −1 with correlation coefficients not less than 0.9979 for the four drugs with the two reagents. The methods are successfully applied to the analysis of pharmaceutical formulations containing amoxicillin, either alone or in combination with potassium clavulanate, flucloxacillin or dicloxacillin. They were also applied to the analysis of the other three studied drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 99.7 (±0.46) to 100.32 (±1.05) in the Ce (IV) method and 99.6 (±0.50) to 100.3 (±1.32) in the Fe (III) method. Interferences from other antibiotics and additives products were investigated.

Selective spectrophotometric method for the determination of ascorbic acid in pharmaceutical preparations and fresh fruit juices

A simple and selective method for the determination of ascorbic acid in pharmaceutical preparations and fresh fruit juices is described. The procedure is based on the reaction of ascorbic acid with the zinc chloride salt of diazotized 1-aminoanthraquinone (Fast Red AL salt) in an acidic medium, followed by development of a blue colour (λmax 630 nm) in alkaline solution. Different variables affecting the colour development were studied and optimized. The method was used to determine between 5 and 25 µg ml–1 of ascorbic acid in the final measured solution. The simplicity of the method permits rapid analysis, suitable for routine control. The method is highly specific for the determination of ascorbic acid in the presence of dehydroascorbic acid and all other vitamins normally encountered with it in pharmaceutical dosage forms. Moreover, the proposed method can also be applied to the determination of ascorbic acid in some fresh fruit juices without interference from coloured and other substances present in the fruit extracts. The reliability of the method was established by parallel determinations against the official British pharmacopoeial method.

Two selective spectrophotometric methods for the determination of amoxicillin and cefadroxil

Two simple, rapid and selective spectrophotometric procedures were developed for the determination of amoxicillin and cefadroxil. The methods are based on the selective oxidation of the drugs with N-bromosuccinimide or N-chlorosuccinimide in an alkaline medium to give an intense yellow product (λmax= 395 nm). The reaction conditions were studied and optimized. The reactions obey Beers law over the range 1–20 µg ml–1 for the two drugs with the two reagents. Interferences from other antibiotics, additives and common degradation products were investigated. The proposed methods were applied to the analysis of pharmaceutical formulations containing amoxicillin, either alone or in combination with potassium clavulanate or flucloxacillin. They were also applied to the analysis of some cefadroxil dosage forms. The results obtained compared favourably with those obtained with other reported methods.

Utility of certain π-acceptors for the spectrophotometric determination of some penicillins

Two simple and sensitive spectrophotometric methods are described for the determination of six penicillin derivatives. The methods are based on the reaction of these drugs as n-electron donors with either 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) or 7,7,8,8-tetracyanoquinodimethane (TCNQ) as pi-acceptors, to give a highly coloured radical anion. The coloured products are quantified spectrophotometrically at 460 and 842 nm for DDQ and TCNQ, respectively. The optimization of the different experimental conditions is described. The interference from streptomycin sulphate and common degradation products was also studied. The proposed methods were applied successfully to the determination of the different penicillins investigated, either in pure or dosage forms, with good accuracy and precision. The results were compared with those given by the official United States Pharmacopeial XXI method.

Charge-transfer complexes of barbiturates and phenytoin.

Simple and sensitive spectrophotometric methods are described, for the first time, for the determination of sodium salts of phenobarbital (1), thiopental (2), methohexital (3) and phenytoin (4). The methods are based on the reaction of these drugs as n-electron donors with the sigma-acceptor iodine and various pi-acceptors: 7,7,8,8-tetracyanoquinodimethane; 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; 2,3,5,6-tetrachloro-1,4-benzoquinone; 2,3,5,6-tetrafluoro-1,4-benzoquinone; 2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone; tetracyanoethylene and 2,4,7-trinitro-9-fluorenon. Depending on the solvent polarity, different coloured charge-transfer complexes and radicals were developed. Different variables and parameters affecting the reactions were studied and optimized. The formed complexes were examined by UV/VIS, infrared and (1)H-NMR. Due to the rapid development of colours at ambient temperature, the obtained results were used on thin layer chromatograms for the detection of the investigated compounds. Beers plots were obeyed in a general concentration range of 1-400 mug ml(-1) for the investigated compounds with different acceptors. Interference from some co-formulated drugs was also studied. No interference was observed due to additives commonly present in the pharmaceutical preparations. The proposed methods could be applied successfully to the determination of the investigated compounds in pure and pharmaceutical dosage forms with good accuracy and precision, the recoveries ranged from 98.7+/-0.5 to 101.1+/-0.5%. The results were compared favourably with the official methods.

Kinetic spectrophotometric determination of certain cephalosporins using oxidized quercetin reagent.

A simple, precise and accurate kinetic spectrophotometric method for determination of cefoperazone sodium, cefazolin sodium and ceftriaxone sodium in bulk and in pharmaceutical formulations has been developed. The method is based upon a kinetic investigation of the reaction of the drug with oxidized quercetin reagent at room temperature for a fixed time of 30 min. The decrease in absorbance after the addition of the drug was measured at 510 nm. The absorbance concentration plot was rectilinear over the range 80-400 microg mL(-1) for all studied drugs. The concentration of the studied drugs was calculated using the corresponding calibration equation for the fixed time method. The determination of the studied drugs by initial rate, variable time and rate-constant methods was feasible with the calibration equations obtained but the fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated; the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent agreement and proved that there is no significant difference in the accuracy and precision.

Selective spectrophotometric determination of ascorbic acid in drugs and foods

A new analytical method was developed for the determination of ascorbic acid. The method is based on the reaction of ascorbic acid with 4-chloro-7-nitrobenzofurazane (NBD-Cl) in the presence of 0.2M sodium hydroxide, where a bluish green colour (lambda(max) 582 nm) is developed after dilution with 50% (v/v) aqueous acetone solution. Beers law was obeyed in a concentration range of 5-20 microg ascorbic acid/ml with a good correlation coefficient (r = 0.9990). The method was found to be highly specific for the determination of ascorbic acid in the presence of dehydro-ascorbic acid, all other vitamins and minerals possibly present in multivitamin preparations, rutin, salicylamide, acetyl salicylic acid, paracetamol, caffeine, phenylephrine hydrochloride and dipyrone. Moreover, the proposed procedure was also successfully applied for the determination of ascorbic acid in some canned and fresh fruit juices, some vegetables and infant milk products without interference from coloured and other substances present in the plant extracts.