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An isocratic reversed - phase high performance liquid chromatographic method has been developed and validated to simultaneously determine nicotinic acid, pravastatin sodium, rosuvastatin calcium, atorvastatin calcium, pitavastatin calcium, lovastatin sodium and simvastatin sodium in focus on counterfeit drug detection. Thin-layer chromatography, nuclear magnetic resonance and mass spectrometry have been additionally performed to verify the identification of adulterants of counterfeit herbal medicines. Chromatographic separation was carried out on Inertsil® ODS-3 C18 (4.6 × 150 mm, 5 μm) with isocratic mobile phase elution containing a mixture of acetonitrile: methanol: 25 mM potassium dihydrogen phosphate buffer, pH 2.86 adjusted with 0.1 M o -phosphoric acid (48: 30: 22, v/v / v), at a flow rate of 1 mL/min and with UV detection at 238 nm. The design of experiment methodology, Plackett–Burman and Box–Behnken designs, was used to screen and optimize the mobile phase composition. The validation of the method was also carried out under the International Conference on Harmonization guidelines. The developed method was sensitive, accurate, simple, economical and highly robust, in addition to the comprehensiveness and novelty of this method for separating the seven drugs. The results were statistically compared with the reference methods used Student's t -test and variance ratio F -test at P  < 0.05. [ABSTRACT FROM AUTHOR]

An isocratic reversed-phase high-performance liquid chromatographic method has been developed and validated for the simultaneous determination of aspirin, prasugrel HCl and clopidogrel bisulfate in the presence of clopidogrel-related compound (impurity-A) in focus on counterfeit. This method was used to determine counterfeited antiplatelet drugs in two substandard Indian pharmaceutical products sold on the market in Yemen and two traditional herbal medicines sold on the market in China. Thin layer chromatography and mass spectrometry of counterfeit herbal medicines have additionally been carried out to verify the identification of adulterants. Chromatographic separation was performed on Inertsil ® ODS-3 C18 (4.6 × 250 mm, 5 μm) with isocratic mobile phase elution containing a mixture of acetonitrile: (25 mM) potassium dihydrogen phosphate buffer, pH 2.7 adjusted with 0.1 M o -phosphoric acid (79: 21, v/v), at a flow rate of 1 mL/min and UV detection at 220 nm. Designs of experiment methodology, Plackett–Burman and Box–Behnken designs were used for the screening and optimization of the mobile phase composition. The method validation was also performed in accordance with the International Council on Harmonization (ICH) guidelines. The method developed for routine analysis was found to be sensitive, simple, accurate and highly robust. The results were statistically compared to reference methods using Student's t -test and variance ratio F -test at P  < 0.05. [ABSTRACT FROM AUTHOR]

Aspirin (ASP) (analgesic; anti-inflammatory; anti-platelet), clopidogrel bisulphate (CLP) (anti-platelet) and atorvastatin calcium (ATV) (anti-hyperlipidemia) are co-formulated in several pharmaceutical formulations. Salicylic acid (SAL), clopidogrel carboxylic acid metabolite related impurity A (CLP-RA) and clopidogrel inactiveR-enantiomer related impurity C (CLP-RC) are considered to be the main synthesis impurities and degradation products of ASP and clopidogrel. On the other hand, high efficiency and less elution are the basic requirements of high-speed chromatographic separation. So a comparative study of two simple, precise, and accurate reversed-phase HPLC-UV and UPLC-DAD methods were developed and validated for simultaneous estimation of ASP, CLP and ATV in bulk and capsules and in the presence of SAL, CLP-RA and CLP-RC. An Agilent Eclipse plus C18 (250 mm × 4.6 mm, 5 μm) for HPLC method and an Agilent Eclipse plus C18 (100 × 2.1 mm, 1.7 μm) for UPLC method were used. A gradient mobile phase for HPLC method and an isocratic mobile phase for UPLC, were used. Detection was performed for both methods at 220 nm for ASP, CLP, SAL, CLP-RA and CLP-RC, and at 240 nm for ATV. The propsed UPLC-DAD method had advantages, of being economic on the large scale with relatively much satisfactory results for sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Bambuterol HCl (BMT) (bronchodilator) was subjected to stress alkaline hydrolysis. BMT alkaline degradation product (BMT-DP) was prepared, isolated and verified chemically using Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance (1H-NMR) as well as mass spectrometry. Na benzoate (BNZ) is commonly co-formulated in oral pharmaceutical preparations as a preservative. Subsequently, a simple, selective and valid stability indicating reversed phase high performance liquid chromatography (RP-HPLC) method was developed for simultaneous estimation of BMT and BNZ in the presence of BMT-DP. Chromatographic separation was achieved using an isocratic mobile phase consisting of a mixture of (20 mM)-KH2PO4(containing 0.2% Triethylamine (TEA)v/v), pH adjusted to 3 with orthophosphoric acid]: acetonitrile (70:30,v/v) with a flow rate 1 mL/min at ambient temperature on a Eurospher II C18 (250 mm × 4.6 mm, 5 μm) column. Analysis was carried out with ultraviolet detection at 215 nm for BMT and BMT-DP, and 225 nm for BNZ. Linearity, accuracy and precision were found to be acceptable over a concentration range of (1-120 μg/mL) and (2-240 μg/mL) for BMT and BNZ, respectively. Limits of detection (LODs) for BMT and BNZ were 0.056 and 0.125 μg/mL, whereas limits of quantitation (LOQs) were 0.169 and 0.378 g/mL, respectively. Moreover, the kinetics of alkaline degradation of BMT was investigated. Arrhenius plot was constructed and the apparent pseudo first-order rate constant, half-life time, shelf-life time, and the activation energy of the degradation process could be calculated. [ABSTRACT FROM AUTHOR]

Tioconazole (TCN) (anti fungal) is commonly co-formulated with tinidazole (TND) (antiprotozoal), hydrocortisone acetate (HYD) (anti infalmmatory) and benzyl alcohol (BZL) (preservative) in different pharmaceutical preparations. Tioconazole has three related impurities namely; tioconazole related impurities A, B and C (TCN-RA), (TCN-RB) and (TCN-RC), respectively. As the main purpose of a test for related substances is to control degradation impurities and to limit impurities arising during the synthesis of active ingredients and on the other hand, high efficiency and less elution are the basic requirements of high-speed chromatographic separation. So, two simple, precise, and accurate reversed-phase HPLC-UV and UPLC-DAD methods have been developed and compared for simultaneous estimation of TND, BZL, HYD and TCN in bulk and pharmaceutical formulations in the presence of TCN related impurities. A Eurospher C18 (250 mm × 4.6 mm, 5 μm) for HPLC method and an Eclipse plus C18 (100 × 2.1 mm, 1.7 μm) for UPLC method were used. An isocratic mobile phase consisted of 20 mM anhydrous KH2PO4(containing 0.2% TEAv/v), pH adjusted to 6 with orthophosphoric acid: acetonitrile, (25:75,v/v) for HPLC method and a gradient mobile phase of 20 mM anhydrous KH2PO4(containing 0.2% TEAv/v), pH adjusted to 6 with orthophosphoric acid and acetonitrile mixed in different proportions for UPLC method, were prepared. Flow rate was set at 1.0 mL min-1and 0.3 mL min-1for HPLC and UPLC methods, respectively and the detection was performed for both methods at 295 nm, 210 nm, 245 nm and 225 nm for TND, BZL, HYD and TCN and its related impurities, respectively. The propsed UPLC-DAD method had advantages, of being economic on the large scale with relatively much satisfactory results for linearity, sensitivity and specificity. The two proposed methods are applicable for the purity assessment of TCN in bulk, vaginal tablets and creams. [ABSTRACT FROM PUBLISHER]

Aspirin (ASP) and cilostazol (CST) are used as a combination in pharmaceutical formulations for treatment of strokes. Salicylic acid (SAL) is considered to be one of the main synthesis impurities and a degradation product of ASP. On the other hand, the main related impurities of CST are CST related A, B, and C (CST-RA, CST-RB, and CST-RC), respectively. Furthermore, as high efficiency and less elution are the basic requirements of high-speed chromatographic separation, so, a comparative study of two simple, precise, and accurate reversed-phase HPLC and UPLC methods was developed and validated for simultaneous estimation of ASP and CST in bulk and capsules in the presence of SAL, CST-RA, CST-RB, and CST-RC. A Eurospher II C18 (250 × 4.6 mm2, 5 µm) for HPLC method and an Agilent Zorbax Eclipse Plus C18 (50 × 2.1 mm2, 1.8 µm) for UPLC method were used. A gradient mobile phase of 20 mM anhydrous KH2PO4buffer solution (containing 0.2% triethylamine (TEA), v/v) with pH adjusted to 2.9 using orthophosphoric acid (solution A) and acetonitrile (solution B) mixed in different proportions for HPLC and UPLC methods was prepared. Flow rate was set to 1.0 and 0.3 mL min−1for HPLC and UPLC methods, respectively, and the detection was performed for both methods at 210 nm. It worth noting that the proposed UPLC-DAD assay exhibited relatively much more precision, sensitivity, specificity, and economic and chromatographic separation superiority than proposed HPLC-UV assay. Both developed methods were compared with reference methods to prove its applicability and are suitable for purity assessment of ASP and CST in bulk and capsules. [ABSTRACT FROM PUBLISHER]

Two new hydrolytic products of letrozole were identified and proved to be true degradation products obtained by alkaline and acidic degradation of the drug. The acid and amide forms of the nitrile groups of letrozole were prepared and identified by IR and mass spectroscopic techniques. Subsequently, a simple, precise and selective stability-indicating RPLC method was developed and validated for the determination of letrozole in the presence of its degradation products. Letrozole was subjected to alkali and acid hydrolysis, oxidation, thermal degradation and photo-degradation. The degradation products were well isolated from letrozole. The chromatographic method was achieved usinggradient elution of the drug and its degradation products on a reversed phase Zorbax Eclipse C18 column (100mm x 4.6mm, 3.5μm) using a mobile phase consisting of 0.01M KH2PO4 and methanol at a flow rate of 1mL min-1. Quantitation was achieved with UV detection at 230nm. Linearity, accuracy and precision were found to be acceptable over the concentration range of 0.01-80μgmL-1. The proposed method was successfully applied to the determination of letrozole in bulk, plasma and in its pharmaceutical preparation. [ABSTRACT FROM AUTHOR]