quantification of 4-methylimidazol in nmri mice plasma and cerebrospinal fluid (csf) by using liquid chromatography tandem mass spectrometry

A sensitive method using ion-pair extraction was developed by liquid chromatography tandem mass spectrometry (lc–ms/ms) for measurement of 4-methylimidazole (4-mi) in nmri mice plasma and cerebrospinal fluid (csf). detection was done by electrospray positive ionization mass spectrometry in the multiple-reaction monitoring (mrm) mode. the validation method was applied to quantification of 4-mi in plasma and csf samples using oral doses of 100, 200, and 300 mg/kg in nmri mice. the efficiency of the method was evaluated in terms of linearity (r^2> 0.99), recovery (98–107%, 3 levels) and precision (8–10%, 3 levels, n = 6). limit of detection (lod) and limit of quantification (loq) were 25 ng/ml and 50 ng/ml, respectively. the results obtained showed that the exposure to oral doses of 4-mi in mice makes different concentrations in plasma and csf and causes significant changes in mice. this study was the first report for determination of 4-mi in plasma and csf samples in mice. our results suggest that lc-ms/msbased on ion-pair extraction is a robust method with high detection ability for measurement of 4-mi in plasma and csf samples. therefore, the developed method can be useful for evaluation and monitoring of imidazole derivatives in biological samples.