Background: A combination of alogliptin and pioglitazone is well tolerated. It does not increase the risk of hypoglycemia. In order to study the bioavailability of aloglipitn in the presence of pioglitazone, it is essential to have a method that can simultaneously detect both in human plasma. A protein precipitation-based method was used to determine alogliptin and pioglitazone simultaneously in human plasma. Protein precipitation causes ion suppression or enhancement in detection methods when compared to other methods. Objective: To simultaneously quantify alogliptin and pioglitazone in human plasma by LC-MS/MS based method. Methods: LC-MS/MS method for the simultaneous determination of pioglitazone and alogliptin in human plasma using stable isotope labelled compounds internal standards. The simple and one step solid phase extraction (SPE) was employed to extract the analytes from plasma. The extracted samples were separated on a C18 column by using a 25:75 (v/v) mixture of acetonitrile and 5 mM ammonium formate as the mobile phase at a flow rate of 0.5 mL/min. Results: The calibration curves obtained were linear (r2= 0.99) over the concentration range of 12.0- 2438.0 ng/mL for pioglitazone and 1.0-202.0 ng/mL for alogliptin. The results of the intra- and interday precision and accuracy studies were found to be within the acceptable limits. The analytes were stable under different stability conditions. All the validation results were found to be within the acceptable limits. The total analytical run time was 3.0 min. There was no interference from plasma matrices. Conclusion: The developed method is precise and adequately sensitive for detection and quantification of analytes. Thus, the method can be useful for bioavailability and bioequivalence (BA/BE) studies and routine therapeutic drug monitoring with the desired precision and accuracy.
Synthesis of pyrazole-3-carboxylic acid was progressed via two different protocols, one of which is solid state. Pyrazole-3-carboxylic acid was converted into different derivatives such as ester, urea, amide and nitrile. The amide compound was converted to nitrile using SOCl2 and DMF. Solid state heating of carboxylic acid gave decarboxylated product. Cyclization of tetra-substituted pyrazole with hydrazines resulted in pyrazolopyridazinones. The antimicrobial activities of the synthesized pyrazole derivatives against Bacillus cereus, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, and Saccharomyces cerevisiae were evaluated. One of the pyrazole derivatives which possess nitro group showed antimicrobial activity in only B. cereus, a Gram-positive bacteria, with an MIC of 128 μg/mL.
Background: The immediate automatic systemic monitoring and reporting of adverse drug reaction, improving the efficacy is the utmost need of medical informatics community. The venturing of advanced digital technologies into the health sector has opened new avenues for rapid monitoring. In recent years, data shared through social media, mobile apps and on other social websites has increased manifolds requiring data mining techniques. Objective: The objective of this report is to highlight the role of advanced technologies together with traditional methods to proactively aid in early detection of adverse drug reactions concerned with drug safety and pharmacovigilance. Methods: A thorough search was conducted for papers and patents regarding pharmacivigilance. All articles with respect to relevant subject were explored and mined from public repositories such as Pubmed, Google Scholar, Springer, ScienceDirect (Elsevier), Web of Science, etc. Results: The European Union’s Innovative Medicines Initiative WEB-RADR project emphasized the development of mobile applications and social media data for reporting adverse effects. Only relevant data has to be captured through the data mining algorithms (DMAs) playing an important role in timely prediction of risk with high accuracy using two popular approaches the frequentist and Bayesian approach. The pharmacovigilance at premarketing stage is useful for the prediction of the adverse drug reactions in early developmental stage of a drug. Later postmarketing safety reports and clinical data reports are important to be monitored through electronic health records, prescription-event monitoring, spontaneous reporting databases, etc approaches. Conclusion: The advanced technologies supplemented with traditional technologies is the need of hour for evaluating product’s risk profile and reducing risk in population esp. with comorbid conditions and on concomitant medications.
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