Quantitation of human plasma levels of the anticancer agent carboxyamidotriazole by high-performance liquid chromatography.
The predominant cause of death of cancer patients is growth and metastasis of their tumors. By targeting signal transduction pathways as sites of therapeutic intervention, we have identified a novel anticancer drug carboxyamidotriazole (CAI). A straight-forward and reliable method of detection and quantitation of human CAI plasma levels using solid-phase organic extraction followed by isocratic reversed-phase chromatography is now reported. This assay detected CAI over the concentration range 0.04-10.0 micrograms/ml, which brackets the range shown to be physiologically and biochemically effective. Linearity was demonstrated by linear regression analysis of calibration curves (r2 = 0.999). Equivalence of recovery of extracted versus non-extracted CAI over a broad concentration range was demonstrated (r2 = 0.998, coefficients of variability < 10%). The method was applied to quantitate CAI plasma levels from patients now entered on the Phase I clinical trial underway at the National Cancer Institute.
Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892.
K A
KA
Holmes
S
S
Chaffins
B L
BL
Osborn
L A
LA
Liotta
E C
EC
Kohn
D000970:Antineoplastic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D006247:Harmine / Q000032:analysis / Q000097:blood / Q000652:urine; D006801:Humans; D007202:Indicators and Reagents; D012044:Regression Analysis; D014230:Triazoles / Q000097:blood*
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D014230:Triazoles; D006247:Harmine