title: Quantitation and pharmacokinetics of 1,4-diamino-2,3-dicyano-1,4-bis (2-aminophenylthio) butadiene (U0126) in rat plasma by liquid chromatography-tandem mass spectrometry.
abstract: A simple, robust, and rapid LC-MS/MS method was developed for the quantitation of U0126 and validated in rat plasma. Plasma samples (20 μL) were deproteinized using 200 μL ACN containing 30 ng/mL of chlorpropamide, internal standard. Chromatographic separation performed on an Agilent Poroshell 120 EC-C(18)  column (4.6 × 50 mm, 2.7 μm particle size) with an isocratic mobile phase consisting of a 70:30 v/v mixture of ACN and 0.1% aqueous formic acid. Each sample was run at 0.6 mL/min for a total run time of 2 min per sample. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with positive ESI at m/z 381 → 123.9 for U0126 and m/z 277 → 175 for the internal standard. The standard curve was linear over a concentration range of 20-5000 ng/mL with correlation coefficients greater than 0.9965. Precision, both intra- and interday, was less than 10.1% with an accuracy of 90.7-99.4%. No matrix effects were observed. U0126 in rat plasma degraded approximately 41.3% after 3-h storage at room temperature. To prevent degradation, sample handling should be on an ice bath and all solutions kept at 4°C. This method was successfully applied to a pharmacokinetic study of U0126 at various doses in rats.
authors.affiliation: College of Pharmacy, The Catholic University of Korea, Bucheon, Gyeonggi-do, Korea. baesk@catholic.ac.kr
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Bae
authors.forename: Jee Won
authors.initials: JW
authors.lastname: Hwang
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.forename: Gyu Hwan
authors.initials: GH
authors.lastname: Park
authors.forename: Kee Dong
authors.initials: KD
authors.lastname: Yoon
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Bae
mesh_terms: D000818:Animals; D002070:Butadienes / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D009570:Nitriles / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002070:Butadienes; D009570:Nitriles; C113580:U 0126