Isotopic dilution GC-MS measurement of 4-hydroxyandrostenedione in postmenopausal breast cancer

Using a novel isotopic dilution gas chromatography-mass spectrometry method, the plasma kinetics of 4-hydroxyandrostenedione (4-OHA) after a single i.m. injection of 250 or 500 mg of the drug have been studied in two groups of postmenopausal women affected by advanced breast cancer. Although the mean values of C-Max (the maximum concentration), t(1/2) and AUC (the area under the curve) for the 500 mg dose group were higher, the differences were not statistically significant, possibly because of the high intersubject variability. In addition, the 4-OHA levels in the breast adipose tissue of the quadrant where the tumor was located were measured in another group of women affected by breast cancer who received a 250 mg dose of drug 2, 7 and 15 days before surgical intervention. The tissue concentrations of 4-OHA were more than five times higher than the corresponding plasma concentrations; in addition they correlated significantly with the circulating levels of the drug and showed an exponential disappearance pattern.