title: Determination of 2-aryl-7(3',4'-dialkoxyphenyl)-pyrazolo [1,5-alpha] pyrimidine, a novel phosphodiesterase-4 inhibitor, in rat plasma by liquid chromatography-tandem mass spectrometry.
abstract: A method for assaying a novel phosphodiesterase-4 inhibitor, 2-aryl-7(3',4'-dialkoxyphenyl)-pyrazolo [1,5-alpha] pyrimidine (PDE-310), was developed and validated in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Rat plasma samples were processed by liquid-liquid extraction with ethyl acetate and injected onto the LC-MS-MS system for quantification. PDE-310 and imipramine (i.e., internal standard) were separated using a Gemini C18 column with mixture of acetonitrile and 0.1% formic acid (70:30, v/v) as the mobile phase. The ion transitions monitored were m/z 425.0 → 331.0 for PDE-310 and m/z 281.3 → 86.1 for imipramine in the multiple-reaction monitoring mode. The detector response was specific and linear for PDE-310 concentrations in the range of 0.1-50 µg/mL. The intra-day and inter-day precision and accuracy of the method were determined to be within the acceptance criteria for assay validation guidelines. The recoveries were approximately 85.7 and 88.2% from rat plasma for PDE-310 and imipramine, respectively. PDE-310 was stable under various processing and handling conditions. PDE-310 concentrations were readily measured in rat plasma samples up to 8 h after an intravenous administration of PDE-310, suggesting that the assay is practically useful.
authors.affiliation: Drug Discovery Platform Technology Team, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Kyeong-Ryoon
authors.initials: KR
authors.lastname: Lee
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Song
authors.forename: Yoon-Jee
authors.initials: YJ
authors.lastname: Chae
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Sung-Heum
authors.initials: SH
authors.lastname: Choi
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Jeon
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D058988:Phosphodiesterase 4 Inhibitors / Q000097:blood*; D011720:Pyrazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines