[Analysis of steroids. Part 42. By-products of the ethynylation of 17-ketosteroids (isolation, identification and determination)].
The therapeutically very important 17 alpha-ethynyl steroids are prepared from 17-keto steroids by means of addition of acetylene. Two important side reactions of this procedure are known: the formation of the isomeric beta-ethynyl derivative and the formation of a dimeric product with acetylene bridge. The aim of this paper is to approach this problem from the point of view of impurity profiling of 17 alpha-ethynyl steroids (norethisterone, ethisterone, norgestrel and delta 9(11)-ethisterone) i.e. isolation, identification and quantification of the above mentioned by-products as impurities in the bulk drugs. Capillary gas chromatography is an ideal tool for the separation and quantitative determination of the beta-ethynyl derivatives (20 m long fused silica capillary, I.D 0.2 mm; stationary phase Ultra-2: 5% phenylmethyl silicon gum phase with a film thickness of 0.33 mu; column temperature 240-250 degrees C). The dimeric impurity cannot be determined directly by gas chromatography as it decomposes in the flash heater to the 17 alpha-ethynyl and the 17-keto derivatives. For this reason reversed-phase HPLC was preferred for their separation and quantitation; (column: 250 x 4 mm LiChrosorb RP-18, 10 microns; eluent methanol-water 7:3; UV detector 240 nm). The HPLC method is suitable for the separation and determination of the beta-ethynyl impurities, too. The chemical shifts of the protons and carbon atoms in the vicinity of C-17 in the 1H and 13C NMR spectra of the epimeric 17-ethynyl steroids greatly depend on the configuration of the ethynyl group and for this reason they (especially that of the C-18 are eminently suitable for the characterization of the isomers.(ABSTRACT TRUNCATED AT 250 WORDS)
Laukó
A
A
Richter Gedeon Vegyészeti Gyár Rt., Budapest.
Csehi
A
A
Balogh
G
G
Csizér
E
E
Herényi
B
B
Görög
S
S
D015068:17-Ketosteroids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005003:Ethisterone / Q000032:analysis; D009640:Norethindrone / Q000032:analysis; D009644:Norgestrel / Q000032:analysis
D015068:17-Ketosteroids; D009644:Norgestrel; D005003:Ethisterone; D009640:Norethindrone
Adatok a szteránvázas vegyületek analitikájához 42. 17-Ketoszteroidok etinilezésének melléktermékei (elválasztás, azonosítás, meghatározás).