title: Determination of 5-HT receptor antagonists, MEFWAY and MPPF using liquid chromatography electrospray ionization tandem mass spectrometry in rat plasma and brain tissue.
abstract: 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 3μm 110Å, 50×2.00mm 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 5ng/mL and 1ng/mL were obtained in 50μL brain homogenate and plasma, respectively. The analytical linear ranges of this method were 1-4000ng/mL in plasma and 5-4000ng/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°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.
authors.affiliation: Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-343, Republic of Korea.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zheng
authors.forename: Byung Hoi
authors.initials: BH
authors.lastname: Lee
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Choi
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Ryu
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001549:Benzamides / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D010879:Piperazines / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D011725:Pyridines / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012702:Serotonin Antagonists / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D001549:Benzamides; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; C513891:fluoro-N-(2-(1-(2-methoxyphenyl)-1-piperazinyl)ethyl-N-2-pyridinyl-benzamide); C515664:mefway