Spectrophotometric determination of ceterizine hydrochloride with Alizarin Red S

A simple, rapid and sensitive spectrophotometric method has been developed for the assay of ceterizine hydrochloride (CTZH) in bulk drug and its pharmaceutical preparations. This method is based on the ion-pair complex reaction between CTZH and Alizarin Red S in Clarks-Lubs buffer. The chromogen being extractable with chloroform, could be measured quantitatively at 440 nm. All variables were studied to optimise the reaction conditions. Regression analysis of Beer's Law plot showed good correlation in the concentration range 2.5-22 microg ml(-1). The method has a detection limit of 0.1328 microg ml(-1). The proposed method has been successfully applied for the analysis of the bulk drug and its dosage forms such as tablets and syrups. No interference was observed from common pharmaceutical adjuvants.     

Determination of methylparaben,propylparaben, clotrimazole and its degradation products in topical cream by RP-HPLC

Summary Reversed-phase, high-performance liquid chromatographic (RP-HPLC) methods with UV detection were developed and validated for determination of compounds in a topical cream. The first method describes determination of the active component clotrimazole and two preservatives present in the cream; methylparaben and propylparaben. The second method describes determination of two degradation products of clotrimazole, imidazole and (2-chlorophenyl) diphenylmethanol, in a topical cream after long-term stability tests. Chromatographic separation was on a Purospher RP-18e column; the mobile phase in Method1 for separation of clotrimazole, methylparaben and propylparaben comprises acetonitrile and water (70:30 v/v). For determination of degradations products-imidazole and (2-chlorophenyl) diphenylmethanol—the optimum composition of mobile phase in Method2 was acetonitrile and water (75:25 v/v) apparent pH^* 2.7. Analysis time was <10 min for both methods. The methods were found to be applicable for routine analysis of the active compound clotrimazole, preservatives and degradation products in the pharmaceutical product: topical cream 1% Clotrimazol Cream. Presented at Balaton Symposium '01 on High-Performance Separation Methods, Siófok, Hungary, September 2–4, 2001     

Extractive spectrophotometric determination of some phenothiazine derivatives in pharmaceutical preparations

A simple, accurate, rapid and sensitive spectrophotometric method has been developed for the assay of six phenothiazine derivatives in bulk drug and their pharmaceutical preparations. The method is based on ion-pair complex reaction of phenothiazines with bromocresol green in aqueous acidic buffer. The chromogen, being extractable with chloroform, could be measured quantitatively at 420 nm. All variables were studied in order to optimize the reaction conditions. The proposed method has been successfully applied to the analysis of the bulk drugs and their dosage forms, tablets and injections. No interference was observed from common pharmaceutical adjuvants. Statistical comparison of the results with those of an official method shows excellent agreement and indicates no significant difference in precision.     

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.     

Separation and determination of process-related impurities of erlotinib using reverse-phase HPLC with a photo-diode array detector

A simple and rapid reverse-phase high-performance liquid chromatographic (HPLC) method for the simultaneous separation and determination of erlotinib and its process-related impurities in bulk drugs has been developed. Five process-related impurities of erlotinib have been separated on an Inerstsil ODS-3V (C18) column and detected at 254 nm using a photo diode array (PDA). This HPLC method was successfully applied to the analysis of erlotinib bulk drug. The recoveries of erlotinib and process-related impurities were in the range of 92.86-106.23%, and found to be specific, precise and reliable for the determination of unreacted raw materials, intermediates in the reaction mixtures and bulk drugs.     

Separation,Characterization, and Quantification of Atorvastatin and Related Impurities by Liquid Chromatography-Electrospray Ionization Mass Spectrometry

A method coupling high-performance liquid chromatography with diode-array detector and electrospray ionization mass spectrometry (HPLC-DAD-ESI/MSⁿ) has been developed for the separation and characterization of atorvastatin and its related impurities. The results obtained using positive ion mode showed some diagnostic fragments that are useful for the identification of atorvastatin related impurities in real samples. Quantitative analysis of drug impurities was performed in the multiple reaction monitoring mode. Quantification limits for impurities were in the ranges 21.5–70.8 ng mL^?1. The method was successfully applied to the drug purity evaluation and quantitative determination of atorvastatin related impurities in bulk drugs and pharmaceutical formulations.     

Rapid separation and determination of process-related substances of paracetamol using reversed-phase HPLC with photo diode array as a detector.

A simple and rapid gradient reversed-phase high-performance liquid chromatographic method for simultaneous separation and determination of paracetamol and its related compounds in bulk drugs and pharmaceutical formulations has been developed. As many as nine process impurities and one degradation product of paracetamol have been separated on a Symmetry C18 column (4.6 x 250 mm i.d., particle size 5 microm) with gradient elution using 0.01 M potassium dihydrogen phosphate buffer (pH 3.0) and acetonitrile as mobile phase and photo diode array detection at 215 nm. The chromatographic behavior of all the compounds was examined under variable compositions of different solvents, temperatures, buffer concentrations and pH values. The correlation coefficients for calibration curves for paracetamol as well as impurities were in the range of 0.9951 - 0.9994. The proposed RP-LC method was successfully applied to the analysis of commercial formulations; the recoveries of paracetamol were in the range of 99-101%. The method could be of use not only for rapid and routine evaluation of the quality of paracetamol in bulk drug manufacturing units but also for detection of its impurities in pharmaceutical formulations.     

A validated enantioselective HPLC assay of dexibuprofen in dexibuprofen tablet formulations

A high-performance liquid chromatography-diode array detector (HPLC-DAD) method was developed and validated for the quantitation of dexibuprofen in dexibuprofen tablets using ovomucoid chiral stationary phase (Ultron ES-OVM). The mobile phasewas composed of 0.025 M potassium phosphate dibasic (pH 4.5)-methanol-ethanol (85:10:5 v/v/v). The method was validated for specificity, linearity, range, accuracy, precision and robustness. The method was enantiomerspecific for the determination of dexibuprofen [S-(+)-isomer ibuprofen] in the presence of R-(-)-isomer ibuprofen in bulk drug, pharmaceutical dosage form and under stress degradation. The method was linear over the range 15-35 mg/mL with r2 = 0.9995; accuracy and precision were acceptable with %RSD < 2.0%. The method was found to be specific, precise, accurate, robust and stability-indicating, and can be successfully applied for the routine analysis of dexibuprofen in bulk drug and pharmaceutical dosage form.     

Spectrophotometric determination of clotrimazole and Phenylephrine-HCl in pharmaceutical formulation using 1, 2-naphthoquinone-4-Sulphonic acid sodium salt (NQS) as a chromogenic reagent

A sensitive, rapid and economical spectrophotometric method based on their interaction with NQS reagent in basic medium, which produces orange-colored complexes, has been devised to identify many drugs with amino groups (clotrimazole and phenylephrine-HCl). The maximum absorption for the complexes of clotrimazole and phenylephrine-HCl is 455 and 484 nm, respectively. Beer's law is applicable in the concentration ranges of (2–40) μg/ml for clotrimazole and (0–20) μg/ml for phenylephrine-HCl. The molar absorptivity values are 3931.1760 L/mol.cm and 4521.4074 L/mol.cm of clotrimazole and phenylephrine-HCl respectively with accuracy of 100.0285%–103.1456% and RSD better than 3.3211%. The method has been successfully used to determine these medications in pharmaceutical formulations, and it has been found to be superior to British Pharmacopeia standard procedures. At a 95% confidence level, F and t-tests are less than the tabulated values.     

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 validated HPLC method for determination of Artesunate in bulk and tablet formulation

The simple, accurate and precise HPLC method for determination of Artesunate in bulk and tablet dosage form has been developed. Quantitation of drug was carried out on Jasco HPLC system with HiQ-SiL C₈ column (250 mm × 4.6 mm i.d.), using acetonitrile: 1 M sodium acetate buffer (pH 3 adjusted with o-phosphoric acid) in the ratio 70: 30 as mobile phase. Method was developed using Artemether as internal standard and UV detector set at 220 nm. Linear concentration range was found to be 250–2500 μg/mL. The method has been successfully applied to the analysis of drugs in bulk and pharmaceutical formulation. The method was validated with respect to linearity, precision and accuracy as per the International Conference on Harmonisation guidelines.     

Development and validation of a TLC-densitometry method for quantitative analysis of nefopam hydrochloride beside its degradation products

A quantitative densitometric thin-layer chromatographic method for determination of nefopam hydrochloride in pharmaceutical preparations has been established and validated. Nefopam from the formulations was separated and identified on silica gel 60 F₂₅₄ TLC plates with chloroform-methanol-glacial acetic acid (9: 2: 0.1, v/v/v) as mobile phase. Densitometric quantification was performed at absorbance maximum 266 nm. The method was validated for linearity, sensitivity, precision and recovery in accordance with ICH guidelines. The presented method is selective and specific with potential application in pharmaceutical analysis. Nefopam hydrochloride was subjected to acidic and alkaline hydrolysis at different temperatures. As the method could effectively separate the drug from its degradation products, it can be employed as a stability indicating one.     

Spectrophotometric determination of tranexamic acid in pharmaceutical bulk and dosage forms.

In this study, a simple, fast, accurate and sensitive spectrophotometric method has been developed for the determination of tranexamic acid in bulk and pharmaceutical preparations. The method is based on the reaction of ninhydrin with the primary amino group of tranexamic acid in the basic medium at pH 8.0. The reaction produces a bluish-purple color which absorbs maximally at 565 nm. Beer's law was obeyed in the range of 3-40 microg ml(-1) with molar absorptivity of 5.093 x 10(3) L mol(-1) cm(-1). The effects of various factors such as temperature, heating time, concentration of reagent, color stability and interferences were investigated to optimize the procedure. The results have been validated analytically and statistically. The proposed method has been applied for the determination of tranexamic acid in bulk and pharmaceutical preparations with good results.     

Determination of Rosuvastatin Calcium in its Bulk Drug and Pharmaceutical Preparations by High-Performance Thin-Layer Chromatography

JPC – Journal of Planar Chromatography – Modern TLC - A normal-phase TLC method has been established for the estimation of rosuvastatin calcium in its bulk drug and pharmaceutical...     

Determination of isosorbide dinitrate in pharmaceutical products by HPLC

A high-performance liquid chromatographic (HPLC) assay for isosorbide dinitrate in pharmaceutical formulations is described. The method employs a reversed-phase C18 column with a mobile phase containing methanol/water/acetate buffer and is specific for isosorbide dinitrate with respect to its 2- and 5-mononitrate degradation products and other organic polynitrate esters. The method is applicable to the analysis of the diluted bulk drug and dosage forms, including sublingual, oral, chewable, and timed-release preparations.     

Spectrophotometric determination of tetracycline and oxytetracycline in pharmaceutical preparations

A simple, rapid and sensitive spectrophotometric procedure for the assay of tetracycline hydrochloride and oxytetracycline hydrochloride has been developed. 2,2-Diphenyl-l-picrylhydrazyl (DPH), an intensely violet-coloured stable free radical, is changed in colour on reaction with the antibiotics investigated. The decrease in the intensity of the violet colour is used to measure the concentration of the drug. All measurements are made at 520 nm on methanolic solutions of the drug and reagent, buffered at pH 6. Beer's law is obeyed in the concentration ranges 2.5-15 and 2.5-20 mug/ml for tetracycline and oxytetracycline respectively. The proposed method has been successfully applied to analysis of the bulk drugs and their pharmaceutical formulations.     

Isolation and characterization of process related impurities of olanzapine using HPLC and ESI-MS/MS

An RP-HPLC method for the simultaneous separation and determination of olanzapine (OLZ) and its process impurities in bulk drugs and pharmaceutical formulations was developed. The separation was accomplished on Inertsil ODS 3V (4.6 mm x 250 mm; particle size 5 microm) column using 0.2 M ammonium acetate (pH = 4.50) and ACN as mobile phase in gradient elution mode. The analytes were monitored by a photo diode array (PDA) detector set at 254 nm and the flow rate was kept at 1.0 mL/min. The chromatographic behavior of all the compounds was examined under variable compositions of different solvents, buffer concentrations, and pH. The method was validated in terms of accuracy, precision, and linearity. Four unknown process impurities observed consistently during the analysis of different batches of OLZ were isolated and characterized by ESI-MS/MS, (1)H NMR, and FT-IR. The proposed RP-HPLC method was successfully applied to the analysis of commercial formulations. The method could be of use not only for rapid and routine evaluation of the quality of OLZ in bulk drug manufacturing units but also for the detection of its impurities in pharmaceutical formulations.     

Simultaneous separation and determination of process-related substances and degradation products of venlafaxine by reversed-phase HPLC

A simple and rapid gradient RP HPLC method for simultaneous separation and determination of venlafaxine and its related substances in bulk drugs and pharmaceutical formulations has been developed. As many as four process impurities and one degradation product of venlafaxine have been separated on a Kromasil KR100-5C18 (4.6 mm x 250 mm; particle size 5 microm) column with gradient elution using 0.3% diethylamine buffer (pH 3.0) and ACN/methanol (90:10 v/v) as a mobile phase. The column was maintained at 40 degrees C and the eluents were monitored with photo diode array detection at 225 nm. The chromatographic behaviour of all the compounds was examined under variable compositions of different solvents, temperatures, buffer concentrations and pH. The method was validated in terms of accuracy, precision and linearity as per ICH guidelines. The inter- and intraday assay precision was < 4.02% (%RSD) and the recoveries were in the range of 96.19-101.14% with %RSD < 1.15%. The correlation coefficients (r2) for calibration curves of venlafaxine as well as impurities were in the range of 0.9942-0.9999. The proposed RP-LC method was successfully applied to the analysis of commercial formulations and the recoveries of venlafaxine were in the range of 99.32-100.67 with %RSD <0.58%. The method could be of use not only for rapid and routine evaluation of the quality of venlafaxine in bulk drug manufacturing units but also for the detection of its impurities in pharmaceutical formulations. Forced degradation of venlafaxine was carried out under thermal, photo, acidic, basic and peroxide conditions and the acid degradation products were characterized by ESI-MS/MS, 1H NMR and FT-IR spectral data.     

Spectrophotometric determination of benzydamine HCl, levamisole HCl and mebeverine HCl through ion-pair complex formation with methyl orange

A simple, rapid and sensitive spectrophotometric method has been proposed for the assay of benzydamine HCl (BENZ), levamisole HCl (LEV) and mebeverine HCl (MBV) in bulk and pharmaceutical formulations. The method based on the reaction of the selected drugs with methyl orange (MO) in buffered aqueous solution at pH 3.6. The formed yellow ion-pair complexes were extracted with dichloromethane and measured quantitatively with maximum absorption at 422 nm. The analytical parameters and their effects on the reported systems are investigated. The extracts are intensely colored and very stable at room temperature. The calibration graphs were linear over the concentration range of 2-10 microg ml(-1) for BENZ, 6-24 microg ml(-1) for LEV and 4-14 microg ml(-1) for MBV. The stoichiometry of the reaction was found to be 1:1 in all cases and the conditional stability constant (K(f)) of the complexes have been calculated. The proposed method was successfully extended to pharmaceutical preparations-tablets. Excipients used as additive in commercial formulations did not interfere in the analysis. The proposed method can be recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical technique are of great importance.     

Simultaneous determination of bifonazole and tinctures of calendula flower in pharmaceutical creams by reversed-phase liquid chromatography

The aim of this research was to develop and validate a sensitive, rapid, easy, and precise reversed-phase liquid chromatography (LC) method for stability studies of bifonazole (I) formulated with tinctures of calendula flower (II). The method was especially developed for the analysis and quantitative determination of I and II in pure and combined forms in cream pharmaceutical formulations without using gradient elution and at room temperature. The influence on the stability of compound I of temperature, artificial radiation, and drug II used for the new pharmaceutical design was evaluated. The LC separation was carried out using a Supelcosil LC-18 column (25 cm x 4.6 mm id, 5 microm particle size); the mobile phase was composed of methanol-0.1 M ammonium acetate buffer (85 + 15, v/v) pumped isocratically at a flow rate of 1 mL/min; and ultraviolet detection was at 254 nm. The analysis time was less than 10 min. Calibration graphs were found to be linear in the 0.125-0.375 mg/mL (rI = 0.9991) and 0.639-1.916 mg/mL (rII = 0.9995) ranges for I and II, respectively. The linearity, precision, recovery, and limits of detection and quantification were satisfactory for I and II. The results obtained suggested that the developed LC method is selective and specific for the analysis of I and II in pharmaceutical products, and that it can be applied to stability studies.