Simultaneous determination of metformin and glimepride in pharmaceutical dosage form by reverse-phase liquid chromatography

A simple, rapid, and precise reversed-phase liquid chromatographic method has been developed for the simultaneous determination of metformin in combination with glimepride. Under the developed conditions, good separation of the analytes was achieved in short analysis time. Several parameters affecting the separation of the analytes were studied, including pH and the concentration of SDS. The method is validated and shown to be linear in the range of 25 microg/mL to 150 microg/mL for metformin and 0.1 microg/mL to 0.6 microg/mL for glimepride. The method is applied for the analysis of these analytes in commercially available tablets.     

Simultaneous determination of paracetamol, chlorzoxazone, and related impurities 4-aminophenol, 4'-chloroacetanilide, and p-chlorophenol in pharmaceutical preparations by high-performance liquid chromatography

This paper presents a simple, specific, and precise high-performance liquid chromatographic method for the simultaneous determination of paracetamol (PCM), chlorzoxazone (CXZ), and their related impurities in bulk raw materials and solid dosage forms. The mobile phase consisted of water-methanol-glacial acetic acid (60 + 40 + 2, v/v/v). A column containing octadecylsilane chemically bonded to porous silica particles (Spherisorb ODS 1, 25 cm x 4.6 mm, 5 microm) was used as stationary phase. Detection was performed using a variable wavelength ultraviolet-visible detector set at 272 nm for all compounds. Solutions were injected into the chromatograph under isocratic condition at a constant flow rate of 1.2 mL/min. The method was validated according to International Conference on Harmonization requirements and demonstrates good accuracy and precision and a wide linearity range. The method separates PCM, CXZ, and 3 major impurities [4-aminophenol (4AP), 4'-chloracetanilide (4CA), and p-chlorophenol (PCP)] with fair resolution in less than 15 min. The developed method is rapid and sensitive (limit of detection for 4AP, 4CA, and PCP established at 31.25, 39.06, and 65.16 ng/mL, respectively) and, therefore, suitable for quality control and stability studies of these compounds in dosage forms.     

Simultaneous high-performance liquid chromatographic determination of paracetamol, phenylephrine HCl, and chlorpheniramine maleate in pharmaceutical dosage forms

A rapid, precise, and specific high-performance liquid chromatographic method is described for the simultaneous determination of paracetamol, phenylephrine HCI, and chlorpheniramine maleate in combined pharmaceutical dosage forms. The method involves the use of a microBondapak CN RP analytical column (125 A, 10 microm, 3.9 x 150 mm) at 22 degrees C as the stationary phase with the mixture of acetonitrile and phosphate buffer (pH 6.22, 78:22) as the mobile phase. Derivatization of the drugs is not required. The method is applied to commercial pediatric cough-cold syrups, tablets, and capsules marketed in Turkey. The relative standard deviation for 10 replicate measurements of each drug in the medicaments is always less than 2%.     

Simultaneous spectrophotometric determination of mefenamic acid and paracetamol in pharmaceutical preparations

A spectrophotometric procedure for the simultaneous determination of mefenamic acid and paracetamol in a mixture is described. Using 0.01 M methanolic hydrochloric acid as solvent, the absorbance of the mixture is measured at 248, 279 and 351 nm. The concentration of each component can be calculated by solving two equations using two wavelengths, either 248 and 279 nm or 248 and 351 nm.     

HPTLC method for determination of nevirapine in pharmaceutical dosage form

A sensitive, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of nevirapine both as a bulk drug and in formulations was developed and validated. The solvent system consisted of toluene-carbon tetrachloride-methanol-acetone-ammonia (3.5:3.5:2.0:1.0:0.05, v/v/v/v/v). Densitometric analysis of nevirapine was carried out in the absorbance mode at 289nm. This system was found to give compact spots for nevirapine (R(f) value of 0.44+/-0.02). Nevirapine was subjected to acid and alkali hydrolysis, oxidation, dry heat and wet heat treatment and photodegradation. The drug undergoes degradation under acidic, basic conditions and oxidation. Also the degraded products were well resolved from the pure drug with significantly different R(f) values. Linearity was found to be in the range of 30-1000ng/spot with significantly high value of correlation coefficient. The linear regression analysis data for the calibration plots showed good linear relationship with r(2)=0.998+/-0.002 in the working concentration range of 300ng/spot to 1000ng/spot. The mean value of slope and intercept were 0.073+/-0.005 and 36.78+/-1.50, respectively. The method was validated for precision, robustness and recovery. The limit of detection and quantitation were 5 and 10ng/spot, respectively. As the method could effectively separate the drug from its degradation products, it can be employed as a stability indicating one. Moreover, the proposed HPTLC method was utilized to investigate the kinetics of acid degradation process. Arrhenius plot was constructed and activation energy was calculated.     

Simultaneous voltammetric determination of acetylsalicylic acid,caffeine and paracetamol in pharmaceutical formulations using screen-printed carbon electrode

Electrochemical oxidation of Paracetamol (PAR), Acetylsalicylic acid (ASA) and Caffeine (CAF) was investigated employing square wave stripping voltammetry (SWSV) using screen–printed carbon electrodes (SPCE). Determinations were performed in 0.1 mol L⁻¹ BR buffer (pH 2.0) without accumulation step. SWV were obtained by scanning the potential from 0.00 to 1.40 V employing a scan increment of 4 mV, pulse amplitude 25 mV and frequency of 25 Hz. PAR, ASA and CAF presents oxidation signals at 0.45, 1.03 and 1.32 V. The detection limits were 1.2, 1.7 and 1.7 mg L⁻¹, respectively. The method was applied in the PAR-ASA-CAF determination on pharmaceutical formulations.     

Simultaneous determination of paracetamol,phenylephrine hydrochloride and chlorpheniramine maleate in pharmaceutical preparations using multivariate calibration 1

Resolution of binary mixtures of paracetamol, phenylephrine hydrochloride and chlorpheniramine maleate with minimum sample pre-treatment and without analyte separation has been successfully achieved by methods of partial least squares algorithm with one dependent variable, principal component regression and hybrid linear analysis. Data of analysis were obtained from UV–vis spectra of the above compounds. The method of central composite design was used in the ranges of 1–15 mg L^?1 for both calibration and validation sets. The models refinement procedure and their validation were performed by cross-validation. Figures of merit such as selectivity, sensitivity, analytical sensitivity and limit of detection were determined for all three compounds. The procedure was successfully applied to simultaneous determination of the above compounds in pharmaceutical tablets.     

Simultaneous determination of chlorpheniramine maleate and dexamethasone in a tablet dosage form by liquid chromatography

An accurate, simple, reproducible, and sensible liquid chromatographic method was developed and validated for the determination of chlorpheniramine maleate and dexamethasone in a tablet formulation. The analysis was performed at room temperature on a reversed-phase C18 column with UV detection at 254 nm. The mobile phase consisted of 7.5 mM monobasic potassium phosphate in methanol-water (62.5 + 37.5) at a constant flow rate of 1 mL/min. The method was validated in terms of linearity, precision, accuracy, and specificity by forced decomposition of chlorpheniramine maleate and dexamethasone initiated by using acid, base, water, hydrogen peroxide, heat, and light. The response was linear in the ranges of 0.04-0.12 and 0.006-0.016 mg/mL for chlorpheniramine maleate (r2 = 0.9999) and dexamethasone (r2 = 0.9994), respectively. The relative standard deviation values for intra- and interday precision studies were 2.39 and 2.02, respectively, for chlorpheniramine maleate and 2.39 and 1.25, respectively, for dexamethasone. Recoveries ranged from 95.07 to 101.95% for chlorpheniramine maleate and from 97.75 to 102.10% for dexamethasone.     

Development and validation of a stability-indicating RP-HPLC method for the determination of paracetamol with dantrolene or/and cetirizine and pseudoephedrine in two pharmaceutical dosage forms

A stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed which can separate and accurately quantitate paracetamol, dantrolene, cetirizine and pseudoephedrine. The method was successfully validated for the purpose of conducting stability studies of the four analytes in quality control (QC) laboratories. The stability-indicating capability of the method was demonstrated by adequate separation of these four analytes from all the degradant peaks. A gradient mobile phase system consisting of (A) 50 mmol L⁻¹ sodium dihydrogen phosphate, 5 mmol L⁻¹ heptane sulfonic acid sodium salt, pH 4.2 and (B) acetonitrile was used with Discovery reversed-phase HS C₁₈ analytical column (250 mm × 4.6 mm i.d., 5 μm particle size). Quantitation was achieved with UV detection at 214 nm, based on peak area.The proposed method was validated and successfully applied for the analysis of pharmaceutical formulations and laboratory-prepared mixtures containing the two multicomponent combinations.     

Simultaneous spectrophotometric determination of paracetamol and salicylamide in human serum and pharmaceutical formulations by a differential kinetic method

A rapid, simple, and sensitive differential kinetic method is presented for the determinations of acetaminophen (also known as paracetamol) and salicylamide. The method is based on their oxidation reaction by Fe3+ ion in the presence of 1, 10-phenanthroline as indicator. The reactions can be monitored spectrophotometrically by measuring the increase in the absorbance of the solution at 510 nm. Two times were selected one in which only paracetamol is oxidized by Fe3+ ion and the other in which both drugs are oxidized by Fe3+ ion. The data were evaluated by the proportional equations method. The method allowed the simultaneous determination of paracetamol and salicylamide at concentrations between 0.5-20 and 1-40 microg/mL with relative standard deviations of 3.47 and 2.58%, respectively. The method was applied to the simultaneous determination of paracetamol and salicylamide in human serum and pharmaceutical formulations.     

Simultaneous voltammetric determination of paracetamol and caffeine in pharmaceutical formulations using a boron-doped diamond electrode

A simple and highly selective electrochemical method was developed for the single or simultaneous determination of paracetamol (N-acetyl-p-aminophenol, acetaminophen) and caffeine (3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione) in aqueous media (acetate buffer, pH 4.5) on a boron-doped diamond (BDD) electrode using square wave voltammetry (SWV) or differential pulse voltammetry (DPV). Using DPV with the cathodically pre-treated BDD electrode, a separation of about 550 mV between the peak oxidation potentials of paracetamol and caffeine present in binary mixtures was obtained. The calibration curves for the simultaneous determination of paracetamol and caffeine showed an excellent linear response, ranging from 5.0 × 10⁻⁷ mol L⁻¹ to 8.3 × 10⁻⁵ mol L⁻¹ for both compounds. The detection limits for the simultaneous determination of paracetamol and caffeine were 4.9 × 10⁻⁷ mol L⁻¹ and 3.5 × 10⁻⁸ mol L⁻¹, respectively. The proposed method was successfully applied in the simultaneous determination of paracetamol and caffeine in several pharmaceutical formulations (tablets), with results similar to those obtained using a high-performance liquid chromatography method (at 95% confidence level).     

Simultaneous determination of propacetamol and paracetamol by derivative spectrophotometry

The present paper describes a procedure that phenols in air were preconcentrated in a membrane cell and their content was determined by adsorptive polarography. First, the phenols in air samples were preconcentrated in a membrane cell using 2.0 M NaOH solution, then in a pH 1.3 buffer solution p-bromophenylamine forms a diazoate with NaNO(2), and into the mixture the collected phenols were added to form azo-compound in a pH 13 buffer solution. The azo-compound can be adsorbed at the mercury electrode and yields a sensitive oscillopolarographic wave. Over the range 2.0x10(-8)-2.0x10(-5) M, the peak currents are linearly proportional to the concentration of phenols. The detection limit is 5.0x10(-9) M.     

Determination of Exemestane in bulk and pharmaceutical dosage form by HPTLC

An HPTLC method for analysis of Exemestane in bulk and pharmaceutical formulation has been established and validated. The analyte was separated on aluminium plates precoated with silica gel 60 F₂₅₄. The mobile phase was chloroform:methanol 9.2:0.8 (v/v). Quantification was done by densitometric scanning at 247 nm. Response was a linear function of Exemestane concentration in the range of 100–500 μg mL⁻¹. The limit of detection and quantification for Exemestane were 5.8 and 17.58 μg mL⁻¹, respectively. Average recovery of Exemestane was 100.1, which shows that the method was free from interference from excipients present in the formulation. The established method enabled accurate, precise, and rapid analysis of Exemestane in bulk as well as pharmaceutical formulation.     

Simultaneous determination of paracetamol and caffeine in pharmaceutical formulations and synthetic urine using cork-modified graphite electrodes

Journal of Solid State Electrochemistry - Cork-modified graphite electrodes were used to develop a simple and selective sensor for the simultaneous determination of paracetamol (PAR) and caffeine...     

Anodic voltammetric behavior of resveratrol and its electroanalytical determination in pharmaceutical dosage form and urine

The anodic voltammetric behavior of resveratrol was studied using cyclic and square wave voltammetric techniques. The oxidation of resveratrol is irreversible and exhibits an adsorption controlled process which is of pH dependence. The oxidation mechanism was proposed in this work. The dependence of the current on pH, the concentration and nature of buffer, and scan rate was investigated to optimize the experimental conditions for the determination of resveratrol. It was found that the optimum buffer for the determination of resveratrol is 1.0 × 10⁻³ M KCl + 0.1 M HNO₃ solution with the pH of 1.0. In the range of 5.00 × 10⁻⁹ to 1.65 × 10⁻⁷ M, the current measured by square wave voltammetry presents a good linear property as a function of the concentration of resveratrol. In addition, the reproducibility, precision and accuracy of the method were checked as well. The method was applied for the determination of resveratrol in Chinese patent medicine and diluted urine.     

Spectrophotometric and titrimetric methods for the determination of nordiazepam in pure and pharmaceutical dosage form

A spectrophotometric method and two titrimetric methods for the determination of nordiazepam via its iodobismuthate complex are described. These methods depend on the reaction of nordiazepam with potassium bismuth iodide which give an orange precipitate. Determination of nordiazepam in the precipitated complex is done iodometrically using standard potassium iodate solution or complexometrically using standard EDTA solution and xylenol orange indicator. Alternatively, the complex is dissolved in ethanol and its absorbance is measured at 323 nm. The three methods were applied for the determination of reference samples of nordiazepam in the concentration range of 1–30 mg ml^?1 (for the iodometric method) and of 5–30 mg ml^?1(for the complexometric method) and of 0.04–3.2 mg ml^?1 (for the spectrophotometric method). The proposed methods were applied for the determination of nordiazepam in madar tablets and the validity of the proposed methods was assessed by applying the standard addition technique.     

Stability indicating HPTLC determination of clopidogrel bisulphate as bulk drug and in pharmaceutical dosage form

A sensitive, selective, precise and stability indicating high-performance thin layer chromatographic method of analysis of clopidogrel bisulphate both as a bulk drug and in formulations was developed and validated in pharmaceutical dosage form. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of carbon tetrachloride-chloroform-acetone (6:4:0.15, v/v/v). This system was found to give compact spots for clopidogrel bisulphate (R_f value of 0.30±0.01). Clopidogrel bisulphate was subjected to acid and alkali hydrolysis, oxidation, photodegradation and dry heat treatment. Also the degraded products were well separated from the pure drug. Densitometric analysis of clopidogrel bisulphate was carried out in the absorbance mode at 230 nm. The linear regression data for the calibration plots showed good linear relationship with r²=0.999±0.001 in the concentration range of 200-1000 ng. The mean value of correlation coefficient, slope and intercept were 0.999±0.001, 0.093±0.011 and 8.83±0.99, respectively. The method was validated for precision, accuracy, ruggedness and recovery. The limits of detection and quantitation were 40 and 120 ng per spot, respectively. The drug undergoes degradation under acidic and basic conditions, oxidation and dry heat treatment. All the peaks of degraded product were resolved from the standard drug with significantly different R_f values. This indicates that the drug is susceptible to acid-base hydrolysis, oxidation and dry heat degradation. Statistical analysis proves that the method is reproducible and selective for the estimation of the said drug. As the method could effectively separate the drug from its degradation products, it can be employed as a stability indicating one.     

Simultaneous determination of clopidogrel and aspirin by RP-HPLC from bulk material and dosage formulations using multivariate calibration technique

A rapid, simple, and easy method for the simultaneous determination of clopidogrel and aspirin from bulk material and dosage formulations in the presence of meloxicam as internal standard has been developed. Separation was carried out on a Purospher star C(18) (5 μm, 250 × 4.6 mm) column at ambient temperature. The mobile phase consisted of methanol-water (80:20, v/v), the pH of the mobile phase was adjusted to 3.4 with ortho-phosphoric acid and pumped at a flow rate of 1 mL/min using isocratic pump system. Multivariate chromatographic calibration technique was subjected to high-performance liquid chromatography (HPLC) data for simultaneous quantitative analysis of binary mixtures of clopidogrel and aspirin. HPLC data based on the analyte peak areas were obtained at five wavelengths (225, 230, 235, 240, and 245 nm). The mathematical algorithm of multivariate chromatographic calibration technique is based on the use of the linear regression equations. Calibration plots for clopidogrel and aspirin were constructed at each wavelength by using the peak areas corresponding to the concentrations of each active compound. This multivariate chromatographic method was also applied to a commercial pharmaceutical dosage form containing clopidogrel and aspirin.     

Simultaneous determination of cloramphenicol, salicylic acid and resorcinol by capillary zone electrophoresis and its application to pharmaceutical dosage forms

This study demonstrates the separation of active ingredients in acne formulations (salicylic acid, cloramphenicol and resorcinol in presence of azulene) by capillary zone electrophoresis. Factors affecting their separations were the buffer pH and concentration, applied voltage, sample preparation, and presence of additives. Optimun results were obtained with a 50 mM sodium tetraborate-50 mM sodium phosphate, pH 9.0. The carrier electrolyte gave baseline separation with good resolution, short migration times (<6 min), great reproducibility and accuracy. Calibration plots were linear over at least three orders of magnitude of analyte concentrations, the lower limits of detection being within the range 0.39-1.25 μg ml⁻¹. The procedure was fast and reliable and commercial pharmaceuticals could be analysed without prior sample clean-up procedure.