A novel 96-microwell-based spectrophotometric assay has been developed and validated for determination of olmesartan medoxomil (OLM) in tablets. The formation of a colored charge-transfer (CT) complex between OLM as a n-electron donor and 2, 5-dichloro-3, 6-dihydroxy-1, 4-benzoquinone (p-chloranilic acid, pCA) as a π-electron acceptor was investigated, for the first time, and employed as a basis in the development of the proposed assay. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 490 nm by microwell-plate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient was found between the absorbance and the concentration of OLM in the range of 1-200 μg ml-1. The limits of detection and quantitation were 0.3 and 1 μg ml-1, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from hydrochlorothiazide and amlodipine that are co-formulated with OLM in some formulations. The assay was successfully applied to the analysis of OLM in tablets with good accuracy and precision. The assay described herein has great practical value in the routine analysis of OLM in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50-fold. Although the proposed assay was validated for OLM, however, the same methodology could be used for any electron-donating analyte for which a CT reaction can be performed.

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Binding of therapeutic agents to plasma proteins, particularly to serum albumin, provides valuable information in the drug development. This study was designed to evaluate the binding interaction of neratinib with bovine serum albumin (BSA). Neratinib blocks HER2 signaling and is effective in trastuzumab-resistant breast cancer treatment. Spectrofluorometric, UV spectrophotometric, and fourier transform infrared (FT-IR) and molecular docking experiments were performed to study this interaction. The fluorescence of BSA is attributed to the presence of tryptophan (Trp) residues. The fluorescence of BSA in presence of neratinib was studied using the excitation wavelength of 280 nm and the emission was measured at 300-500 nm at three different temperatures. Neratinib quenched the BSA intrinsic fluorescence by static mechanism. A complex formation occurred due to the interaction leading to BSA absorption shift. The fluorescence, UV- absorption, three dimensional fluorescence and FT-IR data showed conformational changes occurred in BSA after interaction with neratinib. The binding constant values decreased as the temperature increased suggesting an instable complex formation at high temperature. Site I (sub-domain IIA) was observed as the principal binding site for neratinib. Hydrogen bonding and Van der Waals forces were suggested to be involved in the BSA-neratinib interaction due to the negative values of entropy and enthalpy changes.

Background. Thioacetamide (TAA), a class 2B-type carcinogen, is a potent toxicant. Toxicities caused by this compound in various tissues due to oxidative stress, increase of proinflammatory markers, and apoptosis have been reported; however, reports on kidney toxicity are negligible. Resveratrol (RSV), on the other hand, has demonstrated antioxidant and anti-inflammatory effects in different cases. Resveratrol’s protective effects against TAA kidney toxicity were investigated in four rat groups. Methodology. Four groups of rats were studied as follows (n=8): control group, where rats were fed normal diet and water; TAA group, where rats received 0.3% TAA in water for two weeks; RSV group, where rats received 10 mg/kg body weight (bw) of RSV as oral suspension for two weeks; and treated group, where rats orally received 10 mg/kg bw RSV and simultaneously received 0.3% TAA for two weeks. Kidney homogenates from all groups were analyzed for cytokine release (IL-4, TNF-α, and IFN-γ) and oxidative stress (lipid peroxidation, catalase, and 8-OHdG). The serum of rats was analyzed for the quantification of renal function markers (blood urea nitrogen (BUN), creatinine, and creatine kinase). Result. A significant increase in the renal function markers (BUN, 240%; creatinine, 187%; and creatine kinase, 117%), oxidative stress parameters (lipid peroxidation, 192% increase; catalase, 30.5% decrease), cytokines (IL-4, 120%; TNF-α, 129%; and IFN-γ, 133%), and DNA damage was observed in the TAA-treated group. All changes were significantly reversed in the group treated with RSV and TAA (P<0.05) in combination, with no significant difference compared to the control group. Conclusion. We conclude that resveratrol shows protection against TAA toxicity in rat kidney with respect to DNA damage, oxidative stress, renal function and cytokine release.

This study was designed to evaluate the effect of rutin on hepatotoxicity induced by thioacetamide (TAA) in rats. Four groups of male Wistar rats consisting of six rats each were used: Group I: control group; Group II: rats receiving single injection of 300 mg kg−1 body weight of TAA intraperitoneally; Group III: rats administered rutin (10 mg kg−1 body weight) dissolved in saline orally for 2 weeks; and Group IV: rats administered rutin (10 mg kg−1 body weight) dissolved in saline orally for 2 weeks followed by TAA injection last day of second week. All groups were sacrificed after 24 h of treatment and hepatic toxicity was analyzed with respect to liver toxicity markers, liver DNA fragmentation, and histology of liver tissue. Administration of TAA in Wistar rats resulted in significant increase of hepatic markers, DNA fragmentation in the hepatocytes, and changes in histology. Pretreatment of rats with rutin before 2 weeks of TAA assault resulted in the complete reversal of TAA-mediated hepatic toxicity (P < 0.0001 to P < 0.01) with concomitant restoration of DNA fragmentation. This study suggests rutin as a protective agent for restoration of toxicity caused by TAA.