Validation of liquid chromatography assay for the quantitation of (Z)-3-[2,4-dimethyl-5-(2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-1H-pyrrol-3-yl]propionic acid (SU006668) in human plasma and its application to a phase I clinical trial.
The validation of an analytical method to quantify the antiangiogenic, (Z)-3-[2,4-dimethyl-5-(2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-1H-pyrrol-3-yl]propionic acid (SU006668) for pharmacokinetic determination in a phase I clinical trial, is described. HPLC, with a gradient mobile phase and UV detection at 440 nm, was used. SU006668 was extracted from plasma by precipitation of proteins with acetonitrile. The assay was linear from 25 to 2000 ng/ml (r(2)=0.997); sensitive (limit of quantification 25 ng/ml), accurate (RE 2.6-11.9%) and reproducible (inter-batch precision C.V. 3.2%). Pharmacokinetic data for six patients are presented. They show linear pharmacokinetics with a low volume of distribution and induction at doses of 50, 100 and 200 mg/m(2).
Asad
Yasmin
Y
Cancer Research UK Centre for Cancer Therapeutics, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK. yasmin@icr.ac.uk
Cropp
Gillian
G
Adams
Alison
A
O'Donnell
Anne
A
Raynaud
Florence
F
Judson
Ian
I
Workman
Paul
P
D000970:Antineoplastic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D000078183:Oxindoles; D011422:Propionates / Q000097:blood* / Q000493:pharmacokinetics; D011758:Pyrroles / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D007211:Indoles; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles; C412603:orantinib