Vangala Ranga Reddy

Rapid simultaneous determination of telmisartan, amlodipine besylate and hydrochlorothiazide in a combined poly pill dosage form by stability-indicating ultra performance liquid chromatography.

A simple, precise and rapid stability-indicating ultra-performance liquid chromatography (UPLC) method is developed for the simultaneous quantitative determination of Telmisartan, Amlodipine besylate and Hydrochlorothiazide from their innovative poly pill combination drug product in the presence of degradation products. It involves a 100 mm x 2.1 mm, 1.7 μm C-18 column. The separation is achieved on a simple gradient method. The mobile phase A contains a mixture of sodium perchlorate buffer pH 3.2 (0.053M): acetonitrile in the ratio 90:10, v/v, and mobile B contains a mixture of sodium perchlorate buffer pH 3.2 (0.053M): acetonitrile in the ratio 20:80, v/v. The flow rate is 0.6 mL min−1 and the column temperature is maintained at 55°C.The gradient program (T/%B) is set as 0/5, 1.2/5, 1.6/40, 4/40, 4.1/5 and 4.5/5. The detector wavelength is 271 nm for Hydrochlorothiazide and Telmisartan and 237 nm for Amlodipine. The retention times of Telmisartan, Amlodipine, and Hydrochlorothiazide are 3.6 minutes, 3.2 minutes and 0.9 minutes; respectively. The total runtime for the separation of the three active compounds and their degradation products is 4.5 minutes. The described method is validated with respect to system suitability, specificity, linearity, precision and accuracy. The precision of the assay method is evaluated by carrying out six independent assays of T, A and H (0.032 mg mL−1 of T, 0.004 mg mL−1 of A, 0.01 mg mL−1 of H). The accuracy of the method is evaluated in triplicate at three concentration levels, i.e. 50%, 100% and 150% of target test concentration (0.64 mg mL−1 of T, 0.08 mg mL−1 of A, 0.2 mg mL−1 of H). The described method is linear over the range, 16 to 48 μg mL−1 for T, 2 to 6 μg mL−1A and 5 to 15 μg mL−1 for H. The method is fast and suitable for high-throughput analysis allowing the analysis of about 250 samples per working day.

A validated stability indicating ultra performance liquid chromatographic method for determination of impurities in Esomeprazole magnesium gastro resistant tablets

A novel gradient reversed-phase ultra performance liquid chromatographic method has been developed for quantitative determination of Esomeprazole magnesium and its seven impurities in pharmaceutical dosage forms. Chromatographic separation has been achieved on an Acquity BEH C18, 50mm×2.1mm, 1.7μm with buffered mobile phase consisting solvent A (0.04molar (M) glycine (pH 9.0) buffer) and solvent B (mixture of acetonitrile and Milli-Q water in the ratio 90: 10 (v/v); respectively) delivered at flow rate of 0.21mL min(-1) and the detection wavelength 305nm. Resolution of Esomeprazole magnesium and all the seven potential impurities has been achieved greater than 2.0 for all pairs of compounds. The drug was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Esomeprazole magnesium was found to degrade significantly in oxidative and acid hydrolysis stress conditions and stable in base, hydrolytic and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities, thus proved the stability indicating power of the method. The stress samples were assayed against a reference standard and the mass balance was found to be close to 99.1%. So this method was also suitable for Assay determination of Esomeprazole magnesium in pharmaceutical dosage forms. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness.

Nimesulide Based Novel Glycolamide Esters: Their Design, Synthesis, and Pharmacological Evaluation

The nimesulide based novel glycolamide esters were designed and synthesized for the first time via a three-step method starting from nimesulide. Structures of the synthesized compounds were confirmed by spectroscopic analysis. All the synthesized compounds were examined for their cytotoxic effects in vitro, some of which showed significant cytotoxic activities against HCT-15 human colon cancer cell line.

Lewis acid free high speed synthesis of nimesulide-based novel N-substituted cyclic imides

The first synthesis of nimesulide-based novel cyclic imides has been accomplished via the reaction of an amine prepared from nimesulide with appropriate anhydrides in the presence of sodium acetate. Using this process a variety of N-substituted cyclic imides was prepared in good yields in glacial acetic acid. Some of the compounds synthesized showed anti-inflammatory activities when tested in vivo.

N-(4-Methylsulfonamido-3-phenoxyphenyl)-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboximide

The title compound, N-(4-methylsulfonamido-3-phenoxyphenyl)-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboximide was synthesized in high yield by reaction of N-(4-amino-2-phenoxyphenyl)methanesulfonamide and 9,10-dihydroanthracene-9,10-endo-α,β-succinic anhydride in glacial acetic acid. The structure of the compound was fully characterized by IR, 1H and 13C NMR, mass spectral analysis and elemental analysis.

Quantification of halobetasol propionate and its impurities present in topical dosage forms by stability-indicating LC method.

A novel, sensitive, stability-indicating, gradient, reverse-phase high-performance liquid chromatographic method has been developed for quantitative determination of halobetasol propionate and its impurities in topical dosage forms. The chromatographic separation was achieved on a Phenomenex Synergi polar reverse phase, 250 × 4.6 mm, 4 µm column. Mobile phase A comprises a mixture of 0.01 M KH2PO4 buffer containing 0.2% 1-octane sulfonic acid sodium salt (pH 3.0), acetonitrile and methanol in the ratio 80:15:05 (v/v/v), respectively, and mobile phase B contains a mixture of 0.01 M KH2PO4 buffer containing 0.2% 1-octane sulfonic acid sodium salt (pH 3.0), acetonitrile and methanol in the ratio 20:70:10 (v/v/v), respectively. The flow rate is 0.8 mL min(-1). The column compartment temperature is set at 40°C and the detection wavelength is set at 240 nm. The resolutions between Halobetasol propionate and all the impurities are >2.0 for all pairs of compounds. The drug product was subjected to International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The method is validated as per the ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, robustness and ruggedness.

A Validated Stability-Indicating Liquid Chromatographic Method for the Determination of Retapamulin in Topical Dosage Form

A sensitive, stability-indicating reversed-phase high-performance liquid chromatographic method is developed and validated for the quantitative determination of retapamulin in topical dosage form. The chromatographic separation is achieved by using a C18 column (XTerra RP 18 250 × 4.6 mm, 5 µm) at 30°C. The mobile phase comprises a mixture of 0.05M potassium dihydrogen phosphate buffer (pH 6.1), acetonitrile and methanol in the ratio of 35:50:15 (v/v/v). The flow rate is set at 1.0 mL/min and chromatograms are extracted at 243 nm using a photodiode array detector. The method is validated with respect to linearity, accuracy, precision, robustness and forced degradation studies, which further prove the stability-indicating supremacy of the method. During forced degradation studies, retapamulin is observed to be labile to oxidative and base hydrolysis stress and stable in thermal, photolytic and acid hydrolysis stress. The degradation products are well separated from the retapamulin peak, thus proving the stability-indicating superiority of the method. The method is found to be sensitive for retapamulin, with a detection limit of 25 ng/mL and a quantification limit of 80 ng/mL. The proposed method is found to be very sensitive and accurate for the determination of retapamulin in topical dosage form. The method is also demonstrated to be robust, because it is resistant to small variations of chromatographic variables such as pH, mobile phase composition, flow rate and column temperature.

TFAA-H3PO4 mediated rapid and single-step synthesis of mutual prodrugs of paracetamol and NSAIDs

Abstract A clean and operationally simple method has been developed for the preparation of mutual prodrug using paracetamol and various nonsteroidal anti-inflammatory drugs. The methodology involves use of TFAA/H3PO4 in acetonitrile and a variety of mutual prodrugs has been prepared in good yields by using this single-step C–O bond forming reaction.