A routine feasible HPLC analysis for the anti-angiogenic tyrosine kinase inhibitor, sunitinib, and its main metabolite, SU12662, in plasma.
Sunitinib is an oral inhibitor of multiple tyrosine kinase receptors with antitumor activity in metastatic renal cell carcinoma. So far, published methods for analysis of sunitinib and its active metabolite (SU12662) in plasma are exclusively based on mass spectrometry. In the context of a large-scale feasibility pharmacokinetic analysis, we developed an original, simple, high-performance liquid chromatography (HPLC) assay with UV detection. A stability study of sunitinib and SU12662 in different light exposure conditions is presented. Due to photo-instability of the compounds, blood sampling and the whole handling procedure have to be performed quickly and with minimal light exposure (6-7 lx). Following single organic extraction with tert-butyl methyl ether, HPLC analysis was performed on an ODS column and UV detection was monitored at 369 nm (run time 15 min). This assay was selective and sensitive enough (limit of detection approximately 1 ng/ml) to quantify minimal concentrations at steady state (Css min) of sunitinib and SU12662 in treated patients.
Etienne-Grimaldi
Marie-Christine
MC
Oncopharmacology Unit, Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice Cedex 2, France.
Renée
Nicole
N
Izzedine
Hassan
H
Milano
Gérard
G
D020533:Angiogenesis Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D011758:Pyrroles / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D000077210:Sunitinib
D020533:Angiogenesis Inhibitors; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C544393:SU 12662; D000077210:Sunitinib