Abstract
A sensitive high-performance liquid chromatography–positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of dimebon in rat plasma and brain tissue. Following liquid–liquid extraction, 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 320–277 for dimebon and m/ z 407–100 for the internal standard. The assay exhibited a linear dynamic range of 0.25–250 ng/mL for dimebon in rat plasma and brain tissue. Acceptable precision (<11%) and accuracy (100 ± 7%) were obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample made it possible to analyze more than 250 samples per day. The method was successfully applied to quantify dimebon concentrations in a rodent pharmacokinetic study. Moreover, it can be believed that the assay method in rat plasma would facilitate the ease of adaptability of dimebon quantification in human plasma for clinical trials.
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