RESUMO
PIP: The in vivo and in vitro metabolism of norethynodrel was studied in detail, and the configuration and conformation of the major metabolites were established. In both the in vivo and in vitro studies, the initial concentration of the ethynyl steroidal fractions was obtained by using silver nitrate-silica gel columns, further purified with alumina chromatography. Only traces of unchanged norethynodrel were found. The major ethynyl steroidal metabolites from in vitro rabbit liver homogenate studies were isolated in pure form and were found to be idential to the product obtained by reducing norethynodrel with sodium borohydride. Through use of proton nuclear magnetic resonance spectra (NMR) and mass spectra studies, the configurations of the major metabolites of both the in vivo and in vitro systems were identified as 17alpha-ethynyl-3alpha, 17beta-dihydroxy-delta-estrene and 17alpha-ethynyl-3beta, 17beta-dihydroxy-delta-estrene. In humans, both compounds are found as the beta-glucosiduronates in the ratio of 7:3 in favor of the 3alphaisomer. The conformation of the 3alpha-hydroxyl group was shown to be equatorial, while that of the 3beta-epimer was axial.^ieng
