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Steroid sulphatase inhibitors which decrease or prevent the biosynthesis of oestrogens, potentially have an important role in the treatment of breast cancer in postmenopausal women. The non-steroidal sulphatase inhibitor 667 COUMATE has been shown to be active both in vitro and in vivo. The pharmacokinetics of this drug have not been investigated. In preparation for the clinical evaluation of this agent, a sensitive and robust reversed phase high-performance liquid chromatography (HPLC) method was developed for the detection of 667 COUMATE in biological fluids. The sulphatase inhibitor was extracted from plasma with diethyl ether and separated from putative metabolites and endogenous plasma components with a C3-phenyl column. Using this method an extraction efficiency of 76+/-5% and a limit of detection of less than 0.1 ng/ml was achieved. The stability of this agent was investigated under different pH conditions and during storage in plasma at room temperature or -20 degrees C. 667 COUMATE was found to be stable when stored in acidified plasma (pH 4.5) at -20 degrees C. In conclusion, the HPLC method developed is a reproducible and sensitive assay that will enable quantitation of the potent non-steroidal sulphatase inhibitor 667 COUMATE in biological fluids in the forthcoming Phase I clinical trial.


Conference paper

Publication Date





337 - 342


Chemistry, Clinical, Chromatography, High Pressure Liquid, Coumarins, Ether, Humans, Hydrogen-Ion Concentration, Models, Chemical, Sulfonamides, Sulfonic Acids, Temperature, Time Factors