title: Bioanalysis and pharmacokinetics of the p38 MAPkinase inhibitor SB202190 in rats.
abstract: We have developed a sensitive and reproducible high performance liquid chromatography (HPLC)-UV method for the quantification of the p38 MAPkinase inhibitor SB202190 in serum, kidney homogenates and urine samples. Liquid-liquid extraction of SB202190 from the samples was performed using diethylether after adding a derivative of SB202190 as internal standard (I.S.). Chromatography was carried out using a C8 reversed-phase column with an isocratic mobile phase consisting of acetonitrile-water-trifluoroacetic acid (30:70:0.1, v/v/v; pH 2.0). Both drug and I.S. were measured at 350 nm and eluted at 5.0 and 10.6 min, respectively. Peak-height ratios of the drug and the I.S. were used for the quantification of SB202190 from the different matrixes. The limit of quantitation of SB202190 in serum, kidney and urine were 0.25 microg/ml, 1 microg/g and 1 microg/ml, respectively. The average recoveries were 74, 75 and 92% in serum, kidney and urine, respectively. The intra- and inter-day precision (% CV) and accuracy (% bias) were below 15% for all concentrations. The method was successfully applied for a pharmacokinetic study of SB202190 in rats.
authors.affiliation: Department of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Exploration (GUIDE), University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. J.Prakash@rug.nl
authors.forename: Jai
authors.initials: J
authors.lastname: Prakash
authors.forename: Vinay
authors.initials: V
authors.lastname: Saluja
authors.forename: Jan
authors.initials: J
authors.lastname: Visser
authors.forename: Frits
authors.initials: F
authors.lastname: Moolenaar
authors.forename: Dirk K F
authors.initials: DK
authors.lastname: Meijer
authors.forename: Klaas
authors.initials: K
authors.lastname: Poelstra
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Kok
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007093:Imidazoles / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
chemical_list: D007093:Imidazoles; D011725:Pyridines; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole