Stability-indicating and liquid chromatography-mass spectrometry compatible ultra high performance liquid chromatography method was developed for the degradation and drug substances related impurities of Prothionamide. Forced degradation of Prothionamide was carried out under acidic, basic, thermal, oxidative, and photolytic stress conditions. The impurities separation was achieved on Acquity UPLC BEH-C18 (50 mm × 2.1 mm, 1.7 μm) with the mobile phase of 10 mm ammonium acetate pH 6.0 and Acetonitrile in a time gradient mode. Related substances by ultra-performance liquid chromatography method was validated according to ICH tripartite guidelines. Degradation products were isolated by Column chromatography and characterized by liquid chromatography-mass spectrometry, 1 H, and 13 C nuclear magnetic resonance spectroscopy. The developed related substances method showed adequate specificity, sensitivity, accuracy, linearity (0.4-1.5 μg/mL), precision, and robustness in line with ICH tripartite guidelines for validation of analytical procedures. Limits of detection and quantitation were 0.1 and 0.4 μg/mL, respectively, for Prothionamide and all the impurities. The method was found to be linear with a correlation coefficient > 0.99, precise (%RSD < 5.0), robust and accurate (%recovery 85-115%).
Objective: The objective of this research work is to develop a simple, rapid, cost-effective, accurate, precise, and robust stability-indicating reversephase ultra-high performance liquid chromatography method for the quantitative estimation of telmisartan (TEL) and amlodipine (AMD) in combined tablet dosage form.
Methods: The method uses Poroshell 120EC-C18 column (4.6 mm × 50 mm, 2.7 μm) with an optimized mobile phase containing acetonitrile:50 mM ammonium acetate buffer in the ratio (45:55 v/v), pH adjusted to 4.5 with acetic acid. The flow rate was 0.5 ml/min, column temperature at 25°C and detection was monitored by a PDA detector at a wavelength of 245 nm. International Conference on Harmonization (ICH) recommended stress degradation studies were performed on TEL, AMD standard drugs, and tablet formulations; further stressed samples were analyzed by the proposed method.
Results: Major degradation of TEL and AMD was observed under acidic, alkali, hydrolytic and oxidation conditions. The described method was validated as per the ICH guideline and validation parameters such as system suitability, linearity, accuracy, precision, specificity, and robustness results were within acceptable limits.
Conclusion: The method was found to be suitable and accurate for quantitative estimation and stability study of title drugs in pharmaceutical preparations.
Cardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated hearts and blood vessels of rats. The heart and thoracic aorta were tested with six new synthesized thiazole acetic acid derivatives (SMVA-10, SMVA-35, SMVA-40, SMVA-41, SMVA-42 and SMVA-60), and the data obtained were statistically analyzed and compared. Isolated rat hearts were used to record the changes in developed tension and heart rate, while thoracic aortas were used to measure the contractile response, before and after treatments. Analysis of the results indicated a significant (p < 0.01) increase in developed tension with the addition of SMVA-35, SMVA-40, SMVA-41 and SMVA-42, which was augmented in the presence of adrenaline without affecting the heart rate. On the other hand, acetylcholine significantly decreased the developed tension, which was significantly reversed (p < 0.01) in the presence of compounds (SMVA-35 and SMVA-60). However, in the presence of SMVA-35 and SMVA-40, acetylcholine-induced bradycardia was significantly (p < 0.01) reduced. Furthermore, only SMVA-42 induced a dose-dependent contractile response in the isolated blood vessel, which was abolished in the presence of prazosin. Therefore, it can be concluded that some of the new synthesized thiazole derivatives exhibited promising results by raising the developed tension without changing the heart rate or blood vessel function, which could be helpful in failing heart conditions. However, more research is required to fully comprehend the function, mechanism and effectiveness of the compounds.
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