TY - JOUR
T1 - Bioanalysis and pharmacokinetics of the p38 MAPkinase inhibitor SB202190 in rats
AU - Prakash, Jai
AU - Saluja, Vinay
AU - Visser, Jan
AU - Moolenaar, Frits
AU - Meijer, Dirk K.F.
AU - Poelstra, Klaas
AU - Kok, Robbert J.
PY - 2005/11/5
Y1 - 2005/11/5
N2 - 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 μg/ml, 1 μg/g and 1 μg/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.
AB - 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 μg/ml, 1 μg/g and 1 μg/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.
KW - Drug analysis
KW - High performance liquid chromatography
KW - Liquid-liquid extraction
KW - Pharmacokinetic studies
KW - Renal fibrosis
UR - http://www.scopus.com/inward/record.url?scp=26844553336&partnerID=8YFLogxK
U2 - 10.1016/j.jchromb.2005.09.005
DO - 10.1016/j.jchromb.2005.09.005
M3 - Article
C2 - 16183336
AN - SCOPUS:26844553336
SN - 1570-0232
VL - 826
SP - 220
EP - 225
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
IS - 1-2
ER -