In vivo quantification and pharmacokinetic studies of cotinine in mice after smoke exposure by LC-MS/MS.

A sensitive analytical method was developed and validated for the quantification of cotinine in mouse plasma after exposure to smoke of 0.5, 1.0, and 1.5 commercially available cigarettes, using liquid chromatography tandem mass spectrometry. The method was validated over a linear concentration range of 0.075-20.0 ng/mL with the R2 value being higher than 0.99. Both the precision (coefficient of variation; %) and accuracy (relative error; %) were within acceptable criteria of <15%. The lower limit of quantification (LLOQ) for cotinine was 0.075 ng/mL with sufficient specificity, accuracy, and precision. Following exposure to 0.5, 1.0, and 1.5 cigarette smoke, it was observed that the AUC and the Cmax increased linearly as the doses increased. The pharmacokinetics of cotinine was found linear for the range of 0.5-1.5 commercial cigarette smoke. The quantification of the concentration of cotinine in mouse plasma after smoke exposure will facilitate future behavioral and toxicological experiments in animals and may prove useful in predicting cotinine levels in humans during smoking.

Effect of rutin on anxiety-like behavior and activity of acetylcholinesterase isoforms in specific brain regions of pentylenetetrazol-treated mice.

The aim of the present study was to investigate the effect of rutin administration (100 mg/kg/day) to pentylenetetrazol (PTZ)-treated Balb-c mice (60 mg/kg/day), with respect to anxiety-like behavior using both open-field and elevated plus-maze (EPM) tests, and acetylcholinesterase (AChE) activity in salt-soluble (SS) fraction and detergent-soluble (DS) fraction of the cerebral cortex, hippocampus, striatum, midbrain, and diencephalon. Our results demonstrated that the administration of PTZ in 3 doses and the induction of seizures increased significantly anxiety behavior of mice and reduced significantly DS-AChE activity in all brain regions examined, while the reduction in the SS fraction was brain region-specific. Rutin administration to normal mice did not affect their behavior, while it induced a brain region-specific reduction in SS-AChE and a significant decrease in DS-AChE in all brain regions. We demonstrated for the first time that pretreatment of PTZ-mice with rutin (PTZ + Rutin group) prevented the manifestation of anxiety and induced interestingly a further significant reduction on the SS- and DS-AChE activities only in the cerebral cortex and striatum, in comparison with PTZ group. Our results show that rutin exhibits an important anxiolytic effect and an anticholinesterase activity in specific brain areas in the seizure model of PTZ.