Determination of SU5416, a novel angiogenesis inhibitor, in human plasma by liquid chromatography.
A high-performance liquid chromatographic (HPLC) assay with UV detection has been developed for the quantitative determination of the antiangiogenic agent SU5416 in human plasma. Sample pretreatment involved a single protein-precipitation step with acetonitrile containing the internal standard, chrysin. Separation of the compounds of interest was achieved on a column packed with HP Zorbax C(8) material (5microm particle size; length: 150mm; i.d.: 4.6mm) using a dual solvent system of 0.01M aqueous ammonium acetate and acetonitrile delivered as a nonlinear gradient at a flow-rate of 1.00ml/min. Simultaneous UV detection was performed at 440nm (SU5416) and 268nm (chrysin). The calibration graph was fit to log-transformed response-concentration data over a range of 10-5000ng/ml. Values for accuracy and precision, obtained from six quality controls analyzed on different days in replicates of 3 or 6, ranged 92.9-109 and 0.8-6.2%, respectively. The developed method was successfully applied to study the pharmacokinetics of SU5416 in a cancer patient receiving the drug as a 1h infusion.
Tohnya
Tanyifor M
TM
Medical Oncology Clinical Research Unit, Clinical Pharmacology Research Core, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA.
Kim
Sonia
S
Fine
Howard A
HA
Dunn
Lara
L
Figg
William D
WD
Sparreboom
Alex
A
D020533:Angiogenesis Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D011758:Pyrroles / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; C116890:Semaxinib