Analysis of steroids. XVI

Summary ⁴-3-Hydroxy- or -acetoxysteroids can be determined as 3,5-dienes by spectrophotometry at 236 nm. This method has been employed for the determination of ethynodiol in contraceptive pills. Possible interferences by co-extracted foreign substances have been prevented by differential spectrophotometry. A combination of this method with the reduction by means of sodium borohydride made possible a determination of ⁴-3-ketosteroid contamination in norethynodrel.

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Analyse von Steroiden. XVI

Zusammenfassung ⁴-3-Hydroxy- oder Acetoxysteroide können in Form von 3,5-Dienen spektrophotometrisch bei 236 nm bestimmt werden. Das Verfahren wurde zur Bestimmung von Ethynodiol in Anticoncipientia verwendet, wobei Störungen durch mitextrahierte Fremdsubstanzen durch Differentialspektrophotometrie verhindert wurden. Durch Kombination dieser Methode mit der Reduktion durch Natriumborhydrid konnte eine Verunreinigung von ⁴-3-Ketosteroid in Norethynodrel bestimmt werden.

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Part of the lecture Differential Spectrophotometry in Pharmaceutical Analysis presented to the F.I.P. Congress, London, September, 1969. Part XV.: Mikrochim. Acta (in press).

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The authors thank Mrs. G. Berhidai, Miss M. Kapàs and Miss J. Sütö for their technical assistance.     

Analysis of steroids. XLI. Ion-pair high-performance liquid chromatographic separation of quaternary ammonium steroids on silica.

A normal-phase ion-pair chromatographic system has been developed for the high-performance liquid chromatographic investigation of pipecuronium bromide (2 beta,16 beta-bis-(N'-dimethyl-l-piperazinyl)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide) and related quaternary ammonium steroids. The use of silica as the stationary phase and a 96:4 mixture of acetonitrile and water containing 0.1 mol/dm3 sodium perchlorate as the eluent with detection at 213 nm enable the potential impurities as well as the hydrolytic and oxidative degradation products of pipecuronium bromide to be separated and detected down to the 0.01% level. The above system is also applicable to the high-performance liquid chromatographic investigation of other quaternary ammonium steroids (pancuronium bromide, vecuronium bromide).     

High-pressure liquid chromatography of steroids.

After a brief discussion of the merits and limitations of high-pressure liquid chromatography (HPLC) relative to other chromatographic methods, special problems in the application to steroids are discussed. Publications on HPLC of steroids are then discussed under the headings of individual classes, arranged generally in the order of increasing polarity.     

Antiinflammatory polymer-bound steroids for topical applications II. Controlled release of the steroids

The release of hydrocortisone and dexamethasone due to hydrolysis of the carbonate linkage from the polymeric supports of poly(oxyethyleneglycol), hydroxypropyl cellulose, and N-vinylpyrrolidone/hydrocortisone–²¹CH₂–vinylcarbonate copolymer was observed in a living system, by induction of αGPDH activity in rat C6 glial cells, and in vitro by a kinetic study of release in aqueous sodium phosphate buffer medium. The glucocorticoid release is pH and temperature dependent and highly sensitive to steric hindrance. In vivo testing on antiinflammatory activity in rats with poly(oxyethyleneglycol) and hydroxypropyl cellulose bound dexamethasone was performed. However, it produced negative results probably due to difficulty in splitting the carbonate linkage in the inflammatory region of acidic pH values.     

Highly beta-selective epoxidation of delta5-unsaturated steroids catalyzed by ketones

A general catalytic and environmentally friendly method for beta-epoxidation of delta5-unsaturated steroids has been developed, which uses ketones as the catalysts and Oxone as the terminal oxidant. A whole range of delta5-unsaturated steroids, which bear different functional groups such as hydroxyl, carbonyl, acetyl, or ketal, as well as different side chains, were conveniently converted to the corresponding synthetically and biologically interesting 5beta,5beta-epoxides with excellent beta-selectivities and high yields.     

Transformed steroids 117. Synthesis of 5α-hydroxy-6-oxosteroids with a δ-lactone ring E

The paper is devoted to the synthesis of steroidal 5-hydroxy-6-oxolactones from ethyl esters of 5,6-dienic acids. By epoxidating the latter it has been shown that, in addition to the usual formation of 5,6-oxides, opening of the 16, 17-oxide ring initially formed takes place and this is accompanied by intramolecular cyclization to a 17,20-dihydroxy--lactone. The trans-opening of the 5,6-epoxide in the epoxy--lactone and subsequent oxidation with N-bromosuccinimide has led to a new representative of steroidal -lactones — the 23,16--lactone of the 3-acetate of 3, 5, 16, 17, 20-pentahydroxy-6-oxo-24-norcholan-23-oic acid.N. D. Zelinskii Institute of Organic Chemistry, Academy of Sciences of the USSR, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 208–213, March–April, 1980.     

Translational energy release and stereochemistry of steroids. 14. Epimeric dihydroxy steroids of the androstane series

The stereochemistry of dihydroxy steroids, both the mode of the A/B ring junctions and the configuration of OH groups, may be determined from translational energy (T50%) measurements for the loss of a CH.3 radical, from the ratios of metastable-ion peak heights to those of the main beam (determined for the dehydration reactions), and by comparing unimolecular and collision-induced, mass-analysed ion kinetic energy spectra of the new main beam of [M-H2O]+ ions (i.e. those formed via dehydration of metastable molecular ions of epimeric hydroxy steroids in the first field-free region of a double-focusing mass spectrometer.