Bioanalysis and pharmacokinetics of the p38 MAPkinase inhibitor SB202190 in rats.
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.
Prakash
Jai
J
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
Saluja
Vinay
V
Visser
Jan
J
Moolenaar
Frits
F
Meijer
Dirk K F
DK
Poelstra
Klaas
K
Kok
Robbert J
RJ
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
D007093:Imidazoles; D011725:Pyridines; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole