pH-Induced Difference Spectrophotometric Methods for Drug Analysis. I. Determination of Indomethacin

Abstract

On the basis of the spectral changes of indometnacin induced by changing the pH of the solvent medium, a method for its determination has been developed. The latter involves absorbance measurement of both acid and alkaline solutions of the compound at 260 nm: the difference between both values is linearly related to concentration in the range 0.4-1.4 mg/100 ml. The mean percentage recovery of authentic samples equal 100.1±0.42 (p=0.05). The method has been applied to the analysis of pharnaceutical preparations; the results obtained as compared to those of the official method indicate warranty of application in routine analysis.     

Utility of p-chloranilic Acid and 2,3 Dichloro-5,6-dicyano p-Benzoquinone (DDQ) for the Spectrophotometric Determination of Triamterene

Abstract

Two simple and sensitive spectrophotometric procedures are suggested for analysis of triamterene. The first procedure is based on the reaction of triamterene with p-chloranilic acid (p-CA) in methylene chloride to form a highly stable coloured product, exhibiting maximum absorbance at λ 530 nm. Beer's law is obeyed in the range of 40–220 μg.ml^?1 with a mean percentage accuracy of 99.98 ± 0.446. Limit of determination is 20 μg.ml^?1. In the second procedure, the drug is determined via charge transfer complex formation with 2,3 dichloro-5,6-dicyano p-benzoquinone (DDQ) using methylene chloride as a solvent. Here the reaction product has two well defined maxima at 460 nm and 530 nm where each has been utilized for quantitative determination. Beer's law is obeyed in concentration ranges of 25–125 μg.ml^?1 and 25–150 μg.ml^?1 with mean percentage accuracies of 99.92 ± 0.449 and 100.00 ± 0.511 for both maxima. 460 and 530 nm. respectively. Limit of determination is 12.5 μg.ml^?1 at both maxima. Optimum conditions for each procedure have been studied and the stoichiometry of both reactions was ascertained using Job's method of continuous variation. The validity of the suggested procedures was assessed by applying the standard addition technique using the drug capsules. Both procedures are statistically analyzed as compared with BP method for analysis of triamterene (non aqueous titration) revealing good accuracy and precision as indicated by t and F tests.     

Determination of ethacrynic acid in pharmaceutical formulations by difference ultraviolet spectrophotometry after derivatisation with N-acetylcysteine

A selective difference spectrophotometric procedure is described for the assay of ethacrynic acid (a diuretic drug) in pharmaceutical dosage forms. The method is based on the reaction of the drug with N-acetylcysteine at pH 7.4 and ambient temperature, affording thiol adducts having different spectral properties, and involves the measurement of the absorbance of the reaction mixture relative to an equimolar solution of unreacted ethacrynic acid. The absorbance at 270 nm (A(270)) and the absorbance difference, delta A=A(270-A(244), obtained from the difference spectrum, were found to be linearly correlated with the drug concentration. The proposed spectrophotometric procedure was applied successfully to the determination of ethacrynic acid in pharmaceutical formulations using a reversed-phase high-performance liquid chromatographic procedure as a reference method.     

Colorimetric and Bromometric Determination of Pirbuterol Hydrochloride

Abstract

Two proposed methods are reported for the quantitation of pirbuterol hydrochloride, namely, (i) colorimetric and (ii) titrimetric methods. The colorimetric method is based on coupling betweem diazotized sulphanilamide and pirbuterol hydrochloride. Under the optimum conditions studied, the coupling product exhibits a maximum at 440 nm. Linear relation between absorbance, A, and concentration of pirbuterol hydrochloride is in the range 5–40 μgml^?1. The mean percentage obtained for capsules (Exirel^R ?15 mg) was 100.8 ± 0.7 whereas mean percentage recovery obtained for the authentic drug was 100.5 ± 0.8.

The titrimetric procedure involves bromination of authentic pirbuterol in acid medium and residual titration of excess bromine. The stoichiometry of the reaction was investigated and infra-red analysis, of the bromoderivative was carried out. When applied to capsules the bromometric method gave mean percentage of 100.18 ± 2.25.     

Determination of quaternary ammonium surfactants in pharmaceutical formulations by the hypochromic effect

A spectrophotometric procedure for determination of the quaternary ammonium salts cetrimide (N,N,N-trimethyl-l-hexadecylammonium bromide), cetylpyridinium chloride (l-hexadecyl-pyridinium chloride) and sapamine [N-(2-dimethylaminoethyl)oleamide acetate] in bulk form and some pharmaceutical formulations, such as eye-drops, disinfectant solutions, creams and tablets, is described. Following TLC separation when necessary, addition of an aqueous solution of the active surfactant to a standard amount of Bromothymol Blue, buffered at pH 7.5, leads to an equivalent decrease of the absorbance at 610 nm, which can be taken as an analytical measure of the drug concentration. Good mean recoveries have been obtained for standard additions of these analytes to pharmaceutical formulations containing them.     

Determination of glimepiride in pharmaceutical formulations using HPLC and first-derivative spectrophotometric methods

Two validated analytical methods have been developed to determine glimepiride in pharmaceutical formulations using HPLC and 1st order derivative spectrophotometric techniques. Employing reverse phase HPLC method, the drug was analyzed by pumping a mixture of acetonitrile and 2% formic acid solution, pH 3.5 (80: 20 v/v) through a C₁₈ column (250 × 4.6 mm, 5 μm) and detecting the eluents at 228 nm. The linearity range was found to be 20–140 μg/mL with mean recovery of 100.52 ± 0.33%. The second method was based on the formation of a complex of the drug with 2,3,5-triphenyl-2H-tetrazolium chloride in basic media. 1st order derivative spectrum made it possible to detect the complex at 413.5 nm. The linearity range was found to be 40–160 μg/mL, with mean recovery of 100.33 ± 0.47%. Both the proposed methods can reliably be used for routine analysis of glimepiride in raw material as well as in pharmaceutical formulations. The article is published in the original.     

A sensitive high-throughput HPLC assay for simultaneous determination of everolimus and clobetasol propionate

A novel sensitive high-throughput high-performance liquid chromatography assay is developed and validated for the simultaneous determination of everolimus and clobetasol propionate in pharmaceutical formulations. The chromatographic separation is achieved on a Zorbax Eclipse XDB-C18 reversed-phase column using a gradient elution, with solvent A: ammonium acetate (pH 6.8; 0.01 M) and solvent B: acetonitrile. The mean recovery ranges from 95.1% to 100.0% for clobetasol propionate and from 97.9% to 103.7% for everolimus. The limit of quantitation for each analyte is 0.02 microg/mL. The percent relative standard deviations are less than 3% for intra- and inter-day analyses. The proposed method can be used for the routine quality control of everolimus and clobetasol propionate in complex pharmaceutical formulations, especially the drug-delivery systems with a low total drug-load.     

Determination of Prifinium Bromide in Six Pharmaceutical Formulations by Reverse-Phase Hplc

Abstract

Prifinium bromide is an anti-cholinergic drug, available commercially in various pharmaceutical formulations such as tablets, suppositories, syrups, and ampoules. The present available analytical methods are time-consuming and range from non-aqueous titration to UV-spectrophotometry to ion-pair visible spectrophotometry. The method reported here is a fast, reliable, and stability-indicating reversed phase HPLC for prifinium bromide in its various pharmaceutical formulations. The mobile phase was 0.03 M ammonium acetate in acetonitrile: water (65:35); the pH was adjusted to 4.0 with glacial acetic acid. The column utilized was (250 mm × 4.6 mm i.d.) Supelcosil LC-8-DB (5μ) and detection was carried at 254 nm. Benzophenone was used as internal standard. The assay was applied to commercial products and the results expressed in (% label claim ± RSD) are (99-58 ± 0.36), (100.50 ± 0.40), (99-95 ± 0.70), (99. 94 ± 0.29), (100.28 ± 0.52), and (99-99 ± 0.57) for six commercial formulations. The method was tested for linearity, recovery, and specificity and was found fast, stability-indicating, and free from interferences. The method can be extended to separate     

Photochemical reactivity of sulfamethoxazole and other sulfa compounds with photodiode array detection

The photochemical activities of six sulfa compounds [sulfacetamide (CET), sulfadiazine (DIA), sulfaguanidine (GUA), sulfamerazine (MER), sulfamethoxazole (SMX), and sulfamethizole (MET)] under different experimental conditions such as photolysis time, solvent and buffer pH are investigated by photodiode array (PDA) spectrophotometry. With no photolysis, the sulfa drugs CET and DIA show no absorbance at 332 nm and the other compounds only modest absorbance. Upon photolysis for 4 min, absorbance enhancements at 332 nm of three to four times for GUA and MET and 12-15 times for SMX and MER are observed. For CET and DIA after photolysis, the (absorbance) l/mg is now approximately 0.01-0.02 units. Although two pH optima of approximately 3-4 and 7 are noted, the optimum solvent for photolysis is ethanol without pH adjustment. For flow injection (FI) with on-line photolysis and PDA detection, a mobile phase of 100% ethanol with a step flow rate from 0.1 to 1 ml/min is used providing a 4-min reaction time. The FI detection limit for SMX with photolysis at 330 nm is 1 mg/l. The relative standard deviation data (n=4) of seven individual points in a calibration curve from 5 to 150 mg/l are 0-4%. The recovery of SMX from pharmaceutical tablets is 99.7% indicating no interference from trimethoprim which is not photochemically active.     

Development and validation of a new high-performance liquid chromatographic method for the loperamid hydrochloride determination in drugs

A selective, precise and new high-performance liquid chromatographic method for the analysis of loperamid hydrochloride in pharmaceutical formulations was developed and validated. The mobile phase consisting buffer (sodium-octansulphonate, triethylamine and ammonium hydroxide) in water: acetonitriie (45: 55, v/v) (pH 3.2). The absorbance was monitored with a DAD detector at 226 nm. The flow rate was 1.5 cm³ min⁻¹. The linearity (r = 0.9947) and the recovery (98.58–100.42%) were found to be satisfactory. The detection and quantitation limits were found to be 0.95 and 3.12 μg cm⁻³. The results demonstrated that the procedure was accurate, precise and reproducible. It can be suitably applied for the estimation of lopera-mid hydrochloride in pharmaceutical formulations. The article is published in the original.     

Stability‐Indicating Methods for the Determination of Rofecoxib

Two stability indicating methods have been developed for determining rofecoxib in the presence of its degradation product. The first suggested method is high performance liquid chromatography (HPLC), in which analysis is carried out using hypersil BDS C18 column (250 × 4.6 mm I.D.) with mobile Phase consisting of 0.05 M phosphate buffer (pH 3.5) and acetonitrile (70:30 v/v). A linear relationship was obtained between the detector response at 225 nm and the corresponding concentration of the studied rofecoxib in the concentration range (1–6 μg / 10 μl) with mean % recovery of 99.80 ± 0.405. The second method depends on the quantitative densitometric evaluation of thin layer chromatograms (HPTLC) with mobil phase consisting of toluene: chloroform: methanol (60: 35: 5 v/v/v) by using fluorescent high performance silica gel 60 plate. A linear relationship was obtained between peak area and the concentration of the cited drug in the range 1–6 μg/spot with a mean % recovery of 99.79 ± 0.185. The suggested methods are precise, accurate, rapid and prove their specificity in the presence of its degradation products. Both procedures are successfully applied to determine the drug in the presence of its degradation product and also in their pharmaceutical formulations.     

New Spectrophotometric Method for Azithromycin Determination

Abstract

Azithromycin (AZT), an antibiotic belonging to the family of macrolides, can be analyzed by a new spectrophotometric method based on the formation of an ion pair between this drug and an inorganic complex of (Mo(V)–thiocyanate) followed by its extraction with dichloroethane. This ion‐association complex shows an orange color and exhibits a maximum absorbance at 469 nm. The experimental conditions of the reaction were studied and optimized. The calibration graph was linear (r=0.9996) over the range 10^?6 M–10^?5 M of AZT. This simple and validated method has been successfully applied to the determination of azithromycin in pharmaceutical formulations with a mean relative standard deviation of 1.07% and mean recovery of 99.66%. The common excipients present in azithromycin formulations did not interfere in its determination. This new spectophotometric method has been applied successfully to illustrate the dissolution profiles of original tablets and generic compounds; hence, it could be employed in routine quality control of azithromycin in pharmaceutical dosage forms.     

A Sensitive Colour Reaction for the Deterination of Primaquine in Pharmaceutical Preparations

Abstract

Primaquine reacts with diszo-p-nitroaniline in acid medium to give an orange yellow colour having and absorption maximum at 478 nm. On rendering the medium alkaline, a bathochromic ahift acompanied by hypochromic effect was revealed; the new maximum is located at 525 nm. The mean percentage recoveries for authentic samples amout to 100+, and 100.21+, 0.9 by the acid and alkaline procedures respectively, (p=0.05). Both methods could be applied to determine primaquine salts in pharmaceutical preparatins; the results obtained were in good agreement with those of the offictial method.     

Voltammetric Determination of Azidothymidine Using Silver Solid Amalgam Electrodes

A new simple and direct electroanalytical method was developed for the determination of azidothymidine in commercial pharmaceutical preparations. It is based on differential pulse voltammetry at silver solid amalgam electrode with polished surface (p‐AgSAE) or surface modified by mercury meniscus (m‐AgSAE). The electroreduction of azidothymidine in basic media at these electrodes gives rise to one irreversible cathodic peak. Its potential in 0.05 mol L^?1 borate buffer, pH 9.3 at ca. ?1050 mV is comparable to that using hanging mercury drop electrode (HMDE). Achieved limits of quantitation are in the 10^?7 mol L^?1 concentration range for both amalgam electrodes. According to the procedure based on the standard addition technique, the recoveries of known amounts of azidothymidine contained in pharmaceutical preparations available in capsules were 101.4±1.8% (m‐AgSAE), 100.3±3.5% (p‐AgSAE) and 102.0±1.0% (HMDE) (n=10). There was no significant difference between the values gained by proposed voltammetric methods and the HPLC‐UV recommended by the United States Pharmacopoeia regarding the mean values and standard deviations.     

Colorimetric Microdetermination of Bromhexine Drug in Aqueous Solution

A simple, accurate and sensitive method for determination of bromhexine hydrochloride drug in aqueous solution has been described. The procedure has been based on the reaction of this drug with an excess amount of p‐dimethylaminobenzaldehyde (DAB) in acidic medium (pH =1.6) and the presence of sodium dodecyl sulfate (SDS). The produced yellow color from this reaction has been followed spectrophotometrically at an absorbance maximum of 430 nm. Microgram amounts of bromhexine hydrochloride can be estimated with an accuracy of better than ±1.5% and a relative standard deviation of less than 3.5%. The method has been used for the determination of 0.41–82.5 μg.mL^?1 with a molar extinction coefficient of 4699.1–3602.3 L.mol^?1.cm^?1. An application of the developed procedure to bulk bromhexine hydrochloride and some of its pharmaceutical preparations has been carried out. The effect of the presence of some other surfactants and common pharmaceutical additives has been investigated. A comparison of the presented method with that in the absence of SDS and the standard method of the British Pharmacopoeia has been explored. The suggestion, according to the results, is to use the developed method as standard in pharmaceutical applications.     

Selective Spectrophotometric Determination of Oxyphenbutazone Using a Chelate Forming Reaction

Abstract

A selective spectrophotometric method for the determination of oxyphenbutazone is described. The method is based on nitrosation reaction and simultaneous formation of copper(II) or cobalt (II) chelate of the nitrosoderivative. The formed chelates are extractable with organic solvents giving yellow solutions whose absorbance are proportional to the concentration of oxyphenbutazone. In addition, the chelate extracts, upon treatment with diethyldithiocarbomate develop an additional indirect method of high selectivity for determining oxyphenbutazone. The developed methods are highly accurate and comparable with an official method.     

Spectrophotometric Studies On Determination of Some Cephalosporins and Amoxycillin With Chlorobenzotriazole and Sodium Hypochlorite

Abstract

Two simple colorimetric methods for the determination of certain cephalosporins (cefaclor and cefadroxil) and amoxycillin sodium are described. The suggested methods depend upon the oxidation of these compounds using sodium hypochlorite (SHC) and 1-chlorobenzotriazole (1-CBT) in alkaline medium and colorimetric measurment of the chromophore formed. The different experimental parameters are studied and incorporated into the procedures. The mean percentages found range from 100.0 ± 0.4 to 100.5 ± 0.9. The proposed methods have been successfully applied to the analysis of some pharmaceutical formulations and the results obtained have been statistically compared with those obtaind using the official methods. The proposed methods are convenient, rapid within the concentration range 15-123 μg. ml^?1.     

Extraction and Spectrophotometric Determination of Neomycin Sulfate in Pharmaceutical Oral Suspensions

Abstract

The conditions of neomycin extraction were studied in pharmaceutical oral suspensions to permit its determination by spectrophotometry after reaction with 2, 4-dinitrofluorobenzene. The best recovery of neomycin was obtained with centrifugation employing water as the extraction agent. The spectrophotometric analysis was carried out in 0.02 M borate buffer (pH 9.0), under ambient conditions after 50 minutes of reaction. The absorbance of the yellow product was measured at 365 nm.     

Kinetic Spectrophotometric Determination of Ranitidine

Two spectrophotometric methods were developed for the determination of ranitidine. The first method was a kinetic spectrophotometric method based on the catalytic effect of ranitidine on the reaction between sodium azide and iodine in an aqueous solution. The calibration graph was linear from 4–24 μg/mL. The drug was determined by measuring the decrease in the absorbance of iodine at 348 nm using a fixed time method. The decrease in the absorbance after 1 minute from the initiation of the reaction was related to the concentration of drug. The detection limit of the procedure was 0.76 μg/mL. The proposed procedure was successfully utilized in the determination of the drug in pharmaceutical preparations with mean recovery in the range of 99.83 ? 101.16%. The second method is a colorimetric method, which depends on the measurement of absorbances of tris (o‐phenanthroline) iron(II) [method 2A] and tris (bipyridyl) iron(II) [method 2B] complexes at 512 nm. The complexes obeyed Beer's law over the concentration range of 2–16 μg/mL and 4–40 μg/mL for methods 2A and 2B, respectively. The developed method has been successfully applied for the determination of ranitidine in bulk drugs and pharmaceutical formulations. The common excipients and additives did not interfere in its determination.     

A New Simple and Sensitive Spectrophotometric Procedure for Determination of Adrenaline

Abstract

A new spectrophotometric procedure is described for the determination of ppm concentrations of adrenaline. The procedure is based on formation of Tris(O-phenanthroline)iron(II) complex (ferroin) upon reaction of adrenaline with an iron(III)-O-phenanthroline mixture in slightly acidic medium. The ferroin complex is then spectrophotometrically measured at 510 nm. In addition to being facile and rapid, the procedure is sufficiently selective and accurate, being particularly suitable for the assay of adrenaline in pharmaceutical formulations; the standard deviation didnot exceed 0.64%.