TY - JOUR T1 - NORETHYNODREL METABOLITES IN HUMAN PLASMA AND URINE JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 197 LP - 205 VL - 183 IS - 1 AU - C. E. COOK AU - MARGARET E. TWINE AU - C. RAY TALLENT AU - MONROE E. WALL AU - RUBIN C. BRESSLER Y1 - 1972/10/01 UR - http://jpet.aspetjournals.org/content/183/1/197.abstract N2 - 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 ER -