title: Validation of a method for the determination of the anticancer agent Combretastatin A1 phosphate (CA1P, OXi4503) in human plasma by HPLC with post-column photolysis and fluorescence detection.
abstract: A validated method for the determination of Combretastatin A1 phosphate (CA1P, OXi4503), a bisphosphate prodrug of the vascular disrupting agent Combretastatin A1 in human plasma has been developed using fluorescence detection after post-column photolysis. The separation used the ion-pairing agent tetrabutylammonium hydrogen sulphate, and this agent was also required to give consistently high recovery from plasma. Initially, the range was shown to be linear (r(2)>0.995) from the LOQ of 0.025 μM to 5 μM, but as the trial progressed to much higher doses, using a lower injection volume, the assay was subsequently subject to limited revalidation to cover the range from 0.05 to 50 μM. Intra-assay precision and accuracy ranged from 2.2 to 11.8% and 1.8 to 13% respectively, and for inter-assay from 4.4 to 14.9% and 1.7 to 6.5%. Mean recovery of OXi4503 from plasma was 80.2%.
authors.affiliation: University of Oxford, Gray Institute for Radiation Oncology and Biology, Department of Oncology, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. michael.stratford@rob.ox.ac.uk
authors.forename: Michael R L
authors.initials: MR
authors.lastname: Stratford
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Folkes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D011756:Diphosphates / Q000097:blood*; D006801:Humans; D016014:Linear Models; D051379:Mice; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D013267:Stilbenes / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D011756:Diphosphates; C465018:Oxi 4503; D013267:Stilbenes