Determination of 5-HT receptor antagonists, MEFWAY and MPPF using liquid chromatography electrospray ionization tandem mass spectrometry in rat plasma and brain tissue

초록

A simple, selective, and sensitive liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was validated for the determination of 4-fluoromethyl-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexane-1-carboxamide (MEFWAY) and 4-fluoro-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)benzamide (MPPF) in rat plasma and brain samples, respectively. Plasma and brain samples were extracted with a mixture of acetonitrile and methanol (1:1, v/v) and then separated on a C-18 column (Gemini 3 mu m 110 angstrom, 50 x 2.00 mm ID, Phenomenex, USA). Quantitation was performed using LC-ESI-MS/MS in multiple-reaction monitoring (MRM) mode with positive ion electrospray ionization (ESI). The limit of quantification (LOQ) of 5 ng/mL and 1 ng/mL were obtained in 50 mu L brain homogenate and plasma, respectively. The analytical linear ranges of this method were 1-4000 ng/mL in plasma and 5-4000 ng/mL in brain homogenate with a correlation coefficients (R-2) greater than 0.9993. The intra- and inter-day precision and accuracy values were within the assay validation guideline (lower than 13.0%). The analytes in plasma and brain samples were stable after three freeze-thaw cycles, long-term storage (one month at -80 degrees C), and short-term (4h) storage at room temperature. The present method was successfully applied to plasma-brain pharmacokinetic studies to investigate brain penetration of a single dose of MEFWAY and MPPF in rats. (c) 2012 Elsevier B.V. All rights reserved.

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