Adsorbents for detection, isolation and evaluation of ethynyl steroids

After the administration of norethisterone to seven human subjects 37\m=.\4 % to 80\m=.\6 % of the dose was excreted in the urine within 5 days. About half of the urinary radioactivity was extractable after acid or enzymatic hydrolysis and about 80 % was extracted by using a serial hydrolytic and extraction procedure. About 15 % of the urinary radioactivity was present as sulphate conjugates. About 5 % of the urinary radioactivity was present in acidic or phenolic compounds. No metabolism ofthe ethynyl group seemed to occur and the Girard reaction showed that about half of the urinary metabolites were ketonic. The metabolites in the glucuronide fraction of urine were predominantly more polar on paper chromatography than tetrahydronorethisterone, whereas in the sulphate fraction most of the metabolites had a polarity similar to the simple reduction products of norethisterone. Two days after injection the plasma still contained about 5 % of the administered dose.

Section: Badioactivity In Urinementioning

confidence: 99%

Metabolism of [4-14c]norethisterone in Women

Kamyab¹,

Fotherby²,

Klopper³

1968

“…for the chromatography of norethisterone metabolites. Silvered florisil was prepared according to Ercoli, Vitali & Gardi (1964). Columns (0-5 cm.…”

Section: Introductionmentioning

confidence: 99%

Metabolism and Tissue Distribution of Norethisterone and Norgestrel in Rabbits

Kamyab¹,

Littleton²,

Fotherby³

1967

After injection of [4-14C]norethisterone or norgestrel labelled with 14C in the ethynyl group into rabbits, 45 % and 57\m=.\4% of the radioactivity was excreted in the urine, mostly within 2 days. Although small amounts of radioactivity were excreted in the expired air of rabbits receiving norgestrel, little metabolism of the ethynyl group occurred. Radioactivity in plasma declined quickly after injection and 24 hr. later less than 0\m=.\5 % of the dose remained in the circulation. Up to 5 hr. after injection large amounts of radioactivity were found in liver, kidney, intestine and bile; a large proportion of the dose appeared to undergo an entero-hepatic circulation. Although the concentration in fat and muscle was low the total amount in these tissues may approach 5%. The uterus contained a high concentration of radioactivity suggesting that this tissue may bind the progestins or their metabolites. By 24 hr. the amount of radioactivity in the tissues had markedly decreased. Small amounts of radioactivity crossed the placenta of pregnant animals near term and small amounts were found in the foetus and amniotic fluid. Within 3 hr. of the injection at least half of the radioactivity in the tissues was in a conjugated form and considerable metabolism of the injected progestins had occurred. Little, if any, norethisterone or norgestrel was present in the tissues. The metabolites of norethisterone were mainly polar compounds showing that hydroxylation of the steroid had occurred, whereas the metabolites of norgestrel appeared to be similar to the compounds produced by partial or complete reduction of the \g=a\,\g=b\-unsaturated ketone grouping in ring A.

“…Since most of the radioactivity was recovered in the 'glucuronide' fraction it alone was subjected to column chromatography on silvered Florisil (Ercoli, Vitali & Gardi, 1964) for the separation of compounds containing ethynyl groups from other urinary steroids as described elsewhere (Kulkarni & Goldzieher, 1969). The ethynyl steroid fraction was chromatographed on Whatman no.…”

Section: Chromatographymentioning

confidence: 99%

Metabolism of [14c]ethynyloestradiol in the Baboon

Kulkarni¹

1970

The amounts of radioactivity in the plasma and in the urine of two normally cycling baboons was studied after intravenous administration of [14C]ethynyloestradiol labelled in the ethynyl side-chain. Within 6 days 76\m=.\9\p=m-\83\m=.\3 % of the dose was excreted in the urine; 36\m=.\4\p=m-\50\m=.\9 % appeared on the day of injection, and radioactivity continued to be excreted to the extent of 2\ m=. \ 4\ p=m-\ 2\ m=. \ 9% even on day 6. Of the urinary conjugates isolated by neutral resin chromatography, enzymic hydrolysis and solvolysis liberated 57\m=.\2\p=m-\ 70\m=.\5% and 14% of radioactivity respectively. Paper chromatography of the \g=b\-glucuronidase-liberated fraction with an intact ethynyl group suggested the presence of at least 11 metabolites. Peaks of radioactivity were found among the more polar compounds which barely moved from the starting line, and among compounds similar in polarity to the administered steroid. The chromatographic results with the metabolites suggest that hydroxylation is an important metabolic pathway for ethynyloestradiol in the baboon.