Stability-indicating analysis of injectable estrogen-androgen combinations in formulations containing corn oil.

A method was developed for the analysis of testosterone 17-enanthate 3-benzilic acid hydrazone, 17-beta-estradiol 3,17-dienanthate, and estradiol benzoate combinations dissolved in an oily vehicle. Testosterone 17-enanthate 3-benzilic acid hydrazone was separated from the other drugs and vehicle components by chromatography on an acetonitrile-infusorial earth column followed by quantitation using UV spectroscopy. The estradiol esters were separated from the oil by an additional chromatographic step using a heptane-silanized infusorial earth column prior to quantitation by GLC. Subjecting formulations to elevated temperatures resulted in detectable losses for testosterone 17-enanthate 3-benzilic acid hydrazone and 17-beta-estradiol 3,17-dienanthate. For both drugs, degradation was due to hydroxysis; the degradation products, testosterone 17-enanthate and 17-beta-estradiol 17-enanthate, did not interfere with the intact drug determination. Methods also were developed to estimate degradation product levels in the formulation.