Efficient and metal-free synthesis of 2-aroyl 7-azaindoles via thermally induced denitrogenative intramolecular annulation of 1,2,3,4-tetrazolopyridines.

A facile and metal-free intramolecular denitrogenative annulation strategy for the preparation of novel 2-aroyl 7-azaindoles has been developed from 3-(tetrazolo[1,5-a]pyridin-8-yl)prop-2-en-1-one in the presence of the deep eutectic solvent Dowtherm A. The valuable features of the protocol include a short reaction time, absence of any metal catalyst, utilization of a eutectic solvent, easy product isolation, and very good yields of novel 2-aroyl 7-azaindoles.

Chromatographic separation and spectroscopic characterization of the E/Z isomers of acrivastine.

A reverse phase high performance liquid chromatography (HPLC) method has been developed for the separation of two geometric isomers of Acrivastine using crude reaction mixture. The resolution between two isomers was found more than 2.9. The geometric isomers have been isolated by preparative HPLC and characterized by spectroscopic techniques, such as NMR, infrared, and MS. The developed method has been validated for the determination of Z-isomer in Acrivastine. The limit of detection and limit of quantification of the Z-isomer were 0.05 and 0.2 µg/ml, respectively. The developed method is precise, linear, accurate, rugged and robust for its intended use.

Development and validation of a stability indicating method for the enantioselective estimation of omeprazole enantiomers in the enteric-coated formulations by high-performance liquid chromatography.

Omeprazole is widely prescribed in the form of enteric-coated formulations, due to the rapid degradation of the drug in the acidic condition of the stomach. In the current article, we are reporting the development and complete validation of a stability indicating chiral high-performance liquid chromatography (HPLC) method for the enantioselective analysis of omeprazole in the enteric-coated formulations. A precise and sensitive enantiomeric separation of omeprazole was obtained on Chiralcel OD-H analytical column (250mm × 4.6 mm, 5µm particle size) using normal phase chromatography. The analysis was performed under UV detection at 301nm wavelength. During method development, the addition of methanol to the mobile phase helped in getting the sharp peaks. The developed method showed linear response over a wide concentration range of 0.39-800µg/ml and the regression coefficients value (r(2)) was obtained more than 0.999 for (S)- and (R)-omeprazole. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for (R)-omeprazole were found to be 0.39 and 0.78 µg/ml, respectively for 5 µl injection volume. The percentage recovery of (R)-omeprazole ranged from 93.5 to 104 in spiked formulation samples and omeprazole sample solution and mobile phase were found to be stable for at least 24 h at room temperature. The proposed method was found to be suitable and accurate for the quantitative determination of undesired enantiomer in the enteric-coated omeprazole formulations.

A reverse phase HPLC method for the separation of two stereo isomers of 2-[4-(methylsulfonyl)phenyl]-3-(3(R)-oxocyclopentyl)propanoic acid.

This study describes successful method development and separation of two stereo isomers of 2-[4-(methylsulfonyl)phenyl]-3-(3(R)-oxocyclopentyl)propanoic acid by reverse phase high-performance liquid chromatography. Baseline resolution was achieved on a J'sphere-ODS-H80 (150 mm × 4.6 mm, 4 µm) column using mobile phase consisting of 0.05% triflouroacetic acid in water-acetonitrile (85:15, v/v) at a flow rate of 1.0 ml/min. The detection was carried out at 228 nm. The title compound, in turn, can be obtained by C-alkylation of methyl 2-[4-(methylthio)phenyl]acetate with 2(S)-iodomethyl-8,8-dimethyl-6,10-dioxaspiro[4.5]decane followed by consecutive hydrolysis and oxidation. The partially validated analytical method (system suitability, peak homogeneity, linearity, precision, robustness, and solution stability) has limit of detection and limit of quantification, 0.15 and 0.50 µg/ml respectively. Alternatively, the new method is being routinely utilized to monitor epimerization of α-carbon of the propanoic acid in the title compound by crystallization-induced dynamic resolution.

A validated UPLC method for the determination of process-related impurities in bulk drug.

An UPLC method has been developed and subsequently validated for the determination of Azathioprine and its process-related impurities. Separation was achieved with Acquity UPLC BEH C18, 100 × 2.1 mm, 1.7 µm column and trifluoroacetic acid (0.05% in water) : acetonitrile as eluent in gradient mode. Flow rate was set at 0.35 mL min-1. UV detection was performed at 220 nm. The method has been validated with respect to specificity, accuracy, precision, linearity, robustness, limit of quantification and limit of detection. The accuracy of the method demonstrated at three levels in the range of 50-150% of the specification limit and the recovery of impurities were found to be in the range of 98 to 102%. The detection limits of the process related impurities ranged between 0.16 and 0.24 µg mL-1. The described method is simple, rapid, linear, precise and robust. The method is useful during process development and quality control of bulk manufacturing.