Validated Stability indicating Spectrophotometric Method for the Determination of Acetazolamide in Dosage Forms through Complex Formation with Palladium (II).

A simple and sensitive spectrophotometric method was developed for the determination of acetazolamide (ACM) in pure form and pharmaceutical preparations. The proposed method is based on the complex formation of acetazolamide with Palladium (II) chloride in acetate buffer pH5.4 and measuring the absorbance at 308 nm. The absorbance- concentration plot was rectilinear over the concentration range of 5-70 µg/ml with a minimum detection limit (LOD) of 0.98 µg/ml, limit of quantification (LOQ) of 2.96 µg/ml, and a molar absorptivity ζ=2.7 × 10(3) L/mol.cm. The factors affecting the absorbance of the formed complex were carefully studied and optimized. The composition of the complex as well as its stability constant was also investigated. The proposed method was applied for the determination of acetazolamide in its tablets and the results obtained were favorably compared with those obtained using the official method. A proposal of the reaction pathway was postulated.

Second-derivative synchronous fluorescence spectroscopy for the simultaneous determination of fluphenazine hydrochloride and nortriptyline hydrochloride in pharmaceutical preparations.

A rapid, simple, and highly sensitive second-derivative synchronous fluorimetric (SDSF) method has been developed for the simultaneous analysis of binary mixtures of fluphenazine hydrochloride (FLZ) and nortriptyline hydrochloride (NTP) in their co-formulated tablets. The method is based upon measurement of the native fluorescence of these drugs at constant wavelength difference (Deltalambda) = 120 nm in acetic acid. The different experimental parameters affecting the fluorescence intensity of the studied drugs were carefully studied and optimized. The fluorescence-concentration plots were rectilinear over the range of 0.25-3.0 and 1-10 microg/ml for FLZ and NTP respectively, with lower detection limits (LOD) of 0.05 and 0.18 microg/ml and quantitation limits of 0.15 and 0.53 microg/ml for FLZ and NTP respectively. The proposed method was successfully applied for the determination of the studied compounds in their synthetic mixtures and in commercial co-formulated tablets. The results obtained were in good agreement with those obtained by the reference methods.

Spectrofluorimetric determination of famotidine in pharmaceutical preparations and biological fluids. Application to stability studies.

A simple, economic, selective, and stability indicating spectrofluorimetric method was developed for the determination of famotidine (FMT); is based on its reaction with 9, 10-phenanthraquinone in alkaline medium to give a highly fluorescent derivative measured at 560 nm after excitation at 283 nm. The fluorescence intensity-concentration plot was rectilinear over the concentration range of 50-600 ng/ml with minimum quantification limit (LOQ) of 13.0 ng/ml and minimum detection limit (LOD) of 4.3 ng/ml. The factors affecting the development of the fluorescence intensity of the reaction product were carefully studied and optimized. The method was applied for the determination of FMT in its dosage forms. The stability of the compound was studied, and the proposed method was found to be stability indicating one. The results obtained were in good agreement with those obtained by the official method. Furthermore, the method was applied for the determination of FMT in spiked and real human plasma. The mean % recovery (n = 4) was found to be 99.94 +/- 0.24, and 105.13 +/- 0.64 for spiked and real human plasma, respectively. The composition of the reaction product as well as its stability constant was also investigated. Moreover, the method was utilized to investigate the kinetics of both alkaline and oxidative induced degradation of the drug. The apparent first order rate constant and half life time of the degradation product was calculated. A proposal of the reaction pathway was postulated.

Spectrofluorimetric Determination of Famotidine in Pharmaceutical Preparations and Biological Fluids through Ternary Complex Formation with Some Lanthanide Ions: Application to Stability Studies.

A simple, sensitive and specific method was developed for the determination of famotidine (FMT) in pharmaceutical preparations and biological fluids. The proposed method is based on ternary complex formation of famotidine (FMT) with EDTA and terbium chloride TbCl3 in acetate buffer of pH 4. Alternatively, the complex is formed via the reaction with hexamine and either lanthanum chloride LaCl3, or cerous chloride CeCl3 in borate buffer of pH6.2 and 7.2 respectively. In all cases, the relative fluorescence intensity of the formed complexes was measured at 580 nm after excitation at 290 nm. The fluorescence intensity - concentration plots were rectilinear over the concentration range of 10-100, 5-70, and 5-60 ng/ml, with minimum quantification limits (LOQ) of 2.4, 2.2, and 5.2 ng/ml, and minimum limits of detection (LOD) of 0.79, 0.74, and 1.7 ng/ml upon using TbCl3, LaCl3, and CeCl3 respectively. The proposed method was applied successfully for the analysis of famotidine in dosage forms and in human plasma. The kinetics of both alkaline and oxidative induced degradation of the drug was studied using the proposed method. The apparent first order rate constant and half life time were calculated. A proposal of the reaction pathways is presented.

Kinetic determination of ribavirin in drug formulations.

Two simple and sensitive kinetic methods were developed for the determination of ribavirin in bulk and in its pharmaceutical preparations using alkaline potassium permanganate as an oxidizing agent. The methods are based upon a kinetic investigation of the oxidation reaction of the drug at room temperature for fixed times of 20 and 30 minutes. In the first method, the absorbance of the colored manganate ion was measured at 610 nm, while in second method the reduction in the absorbance of permanganate was measured at 525 nm. The absorbance concentration plots were linear over the range of 3-15 µg/ml with detection limits of 0.028 µg/ml in the first method and 0.229 µg/ml for the second method. The proposed methods were applied successfully for the determination of the drug in its pharmaceutical formulations, the percentage recoveries were 100.15 ± 1.34, 100.06 ± 0.86 in the first method, and 99.60 ± 0.54, 100.43 ± 0.82 in the second method. The results obtained were compared statistically with those obtained by the official method and showed no significant differences regarding accuracy and precision.

Kinetic spectrophotometric method for the determination of ketoprofen in pharmaceuticals and biological fluids.

A simple and sensitive kinetic method is described for the determination of ketoprofen in pure form, pharmaceuticals and biological fluids. The method utilizes an oxidative- coupling reaction based upon oxidation of 3-methyl-2-benzo-thiazolinone hydrazone hydrochloride (MBTH) with Ce(IV) in presence of HCl, where an electrophilic intermediate (diazonium salt of the reagent) is produced, then couples with ketoprofen yielding a highly colored condensation product. The absorbance is measured after 20 min at 605 nm. Calibration graph was linear over the concentration range of 1-8µg/mL with a minimum detection limit of 0.07 µg/mL. The proposed method was applied successfully to the determination of Ketoprofen in pharmaceutical preparations, plasma and urine. The % recoveries were 100.11 for pure form, 100.10 for tablets and gel, 100.0 for suspension and suppositories, 100.2 for capsules and ampoules and 99.79, 99.9 for plasma and urine. The results obtained were in good agreement with those obtained using reference methods for comparison.

Spectrophotometric determination of penicillamine and carbocisteine based on formation of metal complexes.

A simple spectrophotometric method was developed for the determination of penicillamine and carbocisteine. The method depends on complexation of penicillamine with Ni, Co and Pb ions in acetate buffer pH of 6.3, 6.5 and 5.3, respectively, and carbocisteine with Cu and Ni ions in borate buffer pH of 6.7; 1-70 microg/ml of these drugs could be determined by measuring the absorbance of each complex at its specific lambdamax. The results obtained are in good agreement with those obtained using the official methods. The proposed method was successfully applied for the determination of these compounds in their dosage forms. Also, the molar ratio and stability constant of the metal complexes were calculated and a proposal of the reaction pathway was postulated.

Kinetic spectrophotometric determination of some sulfur containing compounds in pharmaceutical preparations and human serum.

A kinetic spectrophotometric method was developed for the determination of carbocisteine, ethionamide, thioctic acid and penicillamine based on the catalytic effect on the reaction between sodium azide and iodine in aqueous solution. Ten to 100 microg ml(-1) of carbocisteine and ethionamide, 0.1-1 microg ml(-1) of thioctic acid and 0.01-0.1 microg ml(-1) of penicillamine could be determined, respectively, by measuring the decrease in the absorbance of iodine at 348 nm by a fixed time method. The decrease in the absorbance in the first 5 min from the initiation of the reaction is related to the concentration of the drugs. The detection limits were 0.47, 0.71, 0.018 and 9.38 x 10(-4) microg ml(-1) for the four drugs, respectively. The proposed procedure was successfully applied in the determination of these drugs in pharmaceutical preparations and human serum.

Fluorimetric determination of some thiol compounds in their dosage forms.

A simple fluorimetric procedure was adopted for determination of three pharmaceutical compounds containing thiol groups namely, captopril, D-penicillamine and N-acetylcysteine. In this method, the drugs are treated with 1,2-naphthoquinone-4-sulfonic acid. The latter is reduced to 1,2-dihydroxynaphthalene-4-sulfonic acid which has a maximum fluorescence intensity at 480/318 nm (lambdaEm/Ex). The method is sensitive to 0.5-4.5 pg ml(- 1) with minimum detectability 0.05 microg ml(-1) (S/N = 2), and has been applied to determine these three thiols in their dosage forms. The results obtained are compared favourably with those obtained by their pharmacopeial methods.

High-performance liquid chromatographic determination of some amino acids after derivatization with 2-hydroxy-1-naphthaldehyde.

2-Hydroxy-1-naphthaldehyde (HNA) was investigated as a derivatizing reagent for the fluorescence detection of histidine, methionine and tryptophan at 385 and 265 nm. The separation of HNA-derivatized amino acids on a conventional reversed-phase column was achieved in less than 40 min. This method was compared with the reported o-phthaldialdehyde (OPA) method. The procedure was successfully applied to the assay of the pure amino acids in a mixture and their pharmaceutical dosage forms.

Titrimetric determination of captopril in dosage forms.

Two titrimetric methods are proposed for the determination of captopril in pure form or in tablets. In the first method iodide selective electrode is used for indirect titrimetric assay of captopril. This compound forms silver salt in presence of excess silver ions, the excess silver ions are determined potentiometrically with standardized iodide solution and an iodide selective electrode. The second method involves the titrimetric determination of captopril using a new oxidimetric titrant 2.3-dichloro-5.6-dicyano-1.4-benzoquinone (DDQ) in anhydrous acetic acid. The equivalent point is detected potentiometrically using calomel and platinum electrodes. The two methods allow semimicro-determination of captopril, the results by the proposed procedures are in good agreement with those obtained by the official method.

Colorimetric determination of some amino acids containing a sulfur group.

A simple and rapid colorimetric method for the determination of some amino acids containing a sulfur group is described. The studied compounds are cysteine, cystine and methionine. The method is based on the formation of ferroin, from the reaction of the studied drugs with a mixture of iron(III) and 1,10-phenanthroline and measurement of the absorbance at 512 nm. The procedure has been successfully applied to the assay of the pharmaceutical preparations of the studied drugs after thin-layer chromatographic separation and the results of the studied compounds compare favourably with the official methods.

Studies of complex formation between the bromophenol blue and some important aminoquinoline antimalarials.

A simple and rapid colorimetric method for the assay of amodiaquine hydrochloride, chloroquine phosphate and primaquine phosphate is described. The method is based on the interaction of the drug base with bromophenol blue to give a stable ion-pair complex. The spectra of the complex shows a maxima at 415-420 nm with high apparent molar absorptivities. Beer's law was obeyed in the concentration range 1-8, 2-10 and 2-12 micrograms.ml-1 for amodiaquine hydrochloride, primaquine phosphate and chloroquine phosphate respectively. The proposed method was applied to the determination of these drugs in certain formulations and the results were favourably comparable to the official methods.

Stability-indicating first-derivative spectrophotometric determination of furazolidone.

A first derivative (1D) spectrophotometric method is described for the determination of furazolidone in the presence of its degradation product (5-nitrofuraldehyde). The method was based on the direct measurement at the maximum of the first derivative curve for furazolidone at 390 nm, which is the zero crossing point of 5-nitrofuraldehyde thus avoiding interference from the degradation product. 5-Nitrofuraldehyde was determined after thin-layer chromatographic separation using silica gel G254 as the coating substance, and mixture of toluene and 1.4-dioxan (95:5) as the developing system. After separation, furazolidone content and its degradation product, 5-nitrofuraldehyde, could be determined separately by first-derivative spectrophotometry at 390 and 290 nm, respectively. 2.5-25 micrograms ml-1 of furazolidone and 5-nitrofuraldehyde could be determined by this method with good accuracy. The proposed method was successfully applied to determine furazolidone in its tablets and 5-nitrofuraldehyde in expired tablets. The results obtained were in good agreement with those obtained by the official method.

Polarographic determination of metyrosine through treatment with nitrous acid.

A simple and sensitive polarographic method is described for the determination of metyrosine through treatment with nitrous acid. The different experimental parameters affecting the derivatization process, as well as the polarographic analysis were studied. The derivatization product was found to be reducible at the dropping mercury electrode over the whole pH range in Britton Robinson buffers. At pH 5, a well-defined diffusion-controlled cathodic wave was produced. The limiting current versus the concentration plot was linear over the range 8-80 mumol/l in the direct current mode with a detection limit of 0.2 mumol/l. The method was then applied to the determination of metyrosine capsules, and the results obtained were in good agreement with those given by the USP method.

Colorimetric and titrimetric assay of isoniazid.

Two methods are proposed for the determination of isoniazid in pure form or in tablets. In the first method chlorpromazine hydrochloride, when treated with 2-iodoxybenzoic acid as an oxidant in 50% w/v o-phosphoric acid solution, is oxidized to chlorpromazine free radical which absorbs at 530 nm. The red free radical is readily reduced quantitatively by isoniazid to the colourless chloropromazine. The addition of isoniazid to a red solution of chlorpromazine free radical results in a decrease in absorbance in direct proportion to the quantity of isoniazid. This forms the basis for the quantitative determination of micro-quantities of isoniazid (3-18 micrograms ml-1). The second method involves the titrimetric determination of isoniazid using N-bromophthalimide as a titrant. The end-point is determined either directly using methyl red or amaranth as indicator, or by a back titration method in which a known excess of N-bromophthalimide solution is added to isoniazid solution and then the residual unreacted reagent is determined iodometrically. The results by the proposed procedures were in good agreement with those obtained by the official methods.

2-Iodylbenzoic acid as an oxidizing agent for the determination of certain thioxanthene derivatives.

An indirect titrimetric method is described for the determination of chlorprothixene, methixene and thiothixene. A known and excessive volume of 2-iodylbenzoate is added and after a specified time the surplus is determined iodometrically. The method has been applied to the analysis of pharmaceutical preparations containing these drugs and the results obtained compare favourably with those from the pharmacopoeial methods. The method is simple, accurate and precise.

Spectrophotometric determination of chlordiazepoxide and nitrazepam.

The use of ethyl acetoacetate in the spectrophotometric determination of chlordiazepoxide and nitrazepam has been investigated. The procedure is based on coupling the diazotized drugs with ethyl acetoacetate, which possesses an active methylene group. The products have absorption maxima at 408 and 482 nm and apparent molar absorptivities of 2.74 x 10(4) and 4.11 x 10(4) 1.mole(-1).cm(-1), respectively. The method is simple, highly sensitive and suitable for 1-16 mug/ml concentrations of the two compounds, with mean recoveries of 100.3 +/- 1.2 and 99.8 +/- 1.0% respectively.