Quantification of methyllycaconitine, selective α 7 nicotinic receptor antagonist, in rodent plasma and brain tissue by liquid chromatography tandem mass spectrometry - application to neuropharmacokinetics of methyllycaconitine in rats

摘要

A sensitive high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of methyllycaconitine (MLA) in rat plasma and brain tissue. Following acetonitrile protein precipitation, the analyte was separated using a gradient mobile phase on a reversed-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H] + ions, m/z 683-216 for MLA and m/z 260-116 for the internal standard. The assay exhibited a linear dynamic range of 0.5-250ng/mL for MLA in rat plasma and brain tissue. The lower limit of quantification was 0.5ng/mL. Acceptable precision (12%) and accuracy (100±6%) were obtained for concentrations over the standard curve range. The method was successfully applied to quantify MLA concentrations in a rodent pharmacokinetic and brain penetration study.