Tinoridine is a nonsteroidal anti-inflammatory drug and also has potent radical scavenger and antiperoxidative activity. However, metabolism of tinoridine has not been thoroughly investigated. To identify in vivo metabolites, the drug was administered to Sprague-Dawley rats (n = 5) at a dose of 20 mg kg(-1), and blood, urine and feces were collected at different time points up to 24 h. In vitro metabolism was delved by incubating the drug with rat liver microsomes and human liver microsomes. The metabolites were enriched by optimized sample preparation involving protein precipitation using acetonitrile, followed by solid-phase extraction. Data processes were carried out using multiple mass defects filters to eliminate false-positive ions. A total of 11 metabolites have been identified in urine samples including hydroxyl, dealkylated, acetylated and glucuronide metabolites; among them, some were also observed in plasma and feces samples. Only two major metabolites were formed using liver microsomal incubations. These metabolites were also observed in vivo. All the 11 metabolites, which are hitherto unknown and novel, were characterized by using ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry in combination with accurate mass measurements. Finally, in silico toxicological screening of all metabolites was evaluated, and two metabolites were proposed to show a certain degree of lung or liver toxicity.

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The objective of the present study was to develop a controlled release transdermal drug delivery systems of simvastatin using lipid vesicular systems incorporated in a Carbopol gel, which will control the release of drug, increasing the bioavailability of the drug and thus decreasing the dosing frequency of the drug. The thin film hydration method or conventional rotary evaporation sonication method was used to prepare the transfersomes formulation. Experimental results of the present study showed that deformable lipid vesicles improve the transdermal delivery, prolong the release, and improve the site specificity of the lipophilic model drug, simvastatin. The drug diffusion studies showed that a transfersome vesicle follows zero order and mechanism of release follows Peppas model. In vivo study of optimized transfersomal gel formulation on suitable rodent model showed better biological anti-hyperlipidemic activity in comparison with reference formulation. Lipid:surfactant ratio of 85:15 is more effective when compared to other formulations because of its Higher flexibility and lesser particle size.