Assessment of preclinical pharmacokinetics and acute toxicity of pioglitazone and telmisartan combination

The prevalence of hypertension is very common amongst the diabetic patients and is reported as the major cause of mortality in diabetes. Pioglitazone reported to have an ability to alter the blood cholesterol level and cardioprotective efficiency along with its antidiabetic activity. Telmisartan, through activation of PPAR-γ receptor exerts insulin sensitizing property in addition to its primary cardioprotective efficiency. Theoretically, a combination of pioglitazone and telmisartan may be beneficial to effectively control the high blood glucose level and management of coexisting cardiovascular complication in diabetes. The aim of this research was to experimentally evaluate the pharmacokinetic interaction of pioglitazone and telmisartan when are coadministered in rat. Pioglitazone and telmisartan were administered orally as a single dose individually and in combination to the rats. The plasma samples of the pharmacokinetic study were analyzed using a validated LCMS method. The acute toxicity of the combination with a high dose in rats was also evaluated as a part of the determination its safety profile. There was no significant change in pharmacokinetic parameters were resulted due to coadministration of pioglitazone and telmisartan in rat. Absence of major toxicological effect supports the safety of the combination in vivo

Simultaneous determination of pioglitazone and candesartan in human plasma by LC-MS/MS and its application to a human pharmacokinetic study

A simple and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and fully validated for simultaneous quantification of pioglitazone and candesartan in human plasma. Irbesartan was used as an internal standard. The analytes were extracted from human plasma samples by solid-phase extraction technique using a Strata-X 33 μm polymeric sorbent. The reconstituted samples were chromatographed on a C18 column by using a 80:20 (v/v) mixture of acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.8 mL/min. The calibration curves obtained were linear (râ¥0.99) over the concentration range of 15â3000 ng/mL for pioglitazone and 5â608 ng/mL for candesartan. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. A run time of 2.7 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies. Keywords: Pioglitazone, Candesartan, Human plasma, Solid-phase extraction, LC-MS/MS, Pharmacokinetic

Critical Perspective on the Industry-centred Engineering of Single-Crystalline Ni-rich Cathodes

Ever growth in the energy demand has catapulted us to explore various energies. Henceforth, to meet these ends, among the different cathode active materials, nickel (Ni) rich polycrystalline (PC) cathode materials have been known to serve the purpose aptly. Yet, these PC Ni-rich cathode materials have yielded inferior performances with an increase in voltage and temperature. The absence of grain boundaries in the intrinsic structure, high mechanical strength, high thermal stability, and controllable crystal faucet have made SC cathodes a better prospect. Yet, there are challenges to overcome in the SC cathodes, like larger crystals hindering the Li+ transport, which leads to disappointing electrochemical performance. Through this perspective article, we wish to elucidate the crucial factors that facilitate the growth of SC-NCM cathode, viable dopants, and coating materials that could enhance the performance, future scope, and scalability of SC-NCM at the Industrial level

An Ethanol Biosensor Based on Simple Immobilization of Alcohol Dehydrogenase on Fe3O4"Au Nanoparticles

An ethanol biosensor based on alcohol dehydrogenase (ADH) attached to Au seeds decorated on magnetic nanoparticles (Fe3O4"Au NPs) is presented. ADH was immobilized on Fe3O4"Au NPs, which were subsequently fixed by a magnet on a carbon paste electrode modified with 5% (m:m) MnO2. Optimum conditions for the amperometric determination of ethanol with the biosensor were as follows: working potential +0.1 V (vs. Ag/AgCl); supporting electrolyte: 0.1 M phosphate buffer solution at pH 6.8 containing 0.25 mM of the coenzyme (NAD+); working electrode: carbon paste with magnetically attached Fe3O4"Au NPs (0.012 mg . cm(-2) electrode area) with immobilized alcohol dehydrogenase (120 units per cm(2) of electrode area). Linearity between signal and concentration was found for the range from 0.1 to 2.0 M ethanol (r(2) = 0.995) with a detection limit of 0.07 M, a sensitivity of 0.02 mu A . mM(-1) . cm(-2), a reproducibility of 4.0% RSD, and a repeatability of 2.7% RSD. The results for the determination of ethanol in alcoholic beverages showed good agreement with gas chromatography (GC) with recovery of 96.0-108.8%.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3331