%0 Journal Article %A C. E. COOK %A MARGARET E. TWINE %A C. RAY TALLENT %A MONROE E. WALL %A RUBIN C. BRESSLER %T NORETHYNODREL METABOLITES IN HUMAN PLASMA AND URINE %D 1972 %J Journal of Pharmacology and Experimental Therapeutics %P 197-205 %V 183 %N 1 %X After p.o. administration to healthy women, 6,7-3H-norethynodrel (1) was rapidly metabolized. The principal free metabolite extracted from plasma was the 3α-hydroxy compound (3a) from reduction of the 3-ketone of 1, with lesser amounts of its 3β-isomer (3b) and norethindrone (2), and some more polar products. Compounds 2, 3a and 3b were identified by carrier addition analysis and their concentrations estimated by thin-layer radiochromatography. The bulk of metabolite material in plasma consisted of conjugates, and over 95% of urinary metabolites (20% of total dose) were conjugated. At least three types of conjugates were present (two of which were β-glucuronides). After enzymatic hydrolysis of urinary metabolites, compounds 2, 3a and 3b, together with a small amount of an alcohol in which the A-ring was saturated (4b), were identified by gas-liquid chromatography-mass spectrometry. Hydroxylated compounds composed 70 to 80% of the enzymatically hydrolyzed urinary metabolites (thus representing about 10% of the administered dose). The principal hydroxylated compounds isolated were triols (C20H28O3) retaining the double bond and the ethynyl group of 1, as shown by gas-liquid chromatography-mass spectrometry and high resolution mass spectrometry of the trimethylsilyl ethers. Thus reduction of the 3-ketone of 1 is a principal metabolic pathway and is accompanied by hydroxylation. © 1972, by The Williams & Wilkins Company %U https://jpet.aspetjournals.org/content/jpet/183/1/197.full.pdf