title: 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.
abstract: 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).
authors.affiliation: Cancer Research UK Centre for Cancer Therapeutics, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK. yasmin@icr.ac.uk
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Asad
authors.forename: Gillian
authors.initials: G
authors.lastname: Cropp
authors.forename: Alison
authors.initials: A
authors.lastname: Adams
authors.forename: Anne
authors.initials: A
authors.lastname: O'Donnell
authors.forename: Florence
authors.initials: F
authors.lastname: Raynaud
authors.forename: Ian
authors.initials: I
authors.lastname: Judson
authors.forename: Paul
authors.initials: P
authors.lastname: Workman
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles; C412603:orantinib