16α-Hydroxy Steroids. VII.¹ The Isomerization of Triamcinolone

Abstract

Triamcinolone and triamcinolone 16a,2 1-diacetate have been characterized by ultraviolet absorption spectra, infrared absorption spectra, absorption spectra in sulfuric acid, polarogra hy, reduction of tetrazolium blue, and by Porter-Silber chromogens. The use of agsorption spectra, polarography, and colorimetry for quantitative determination of bulk triamcinolone and of triamcinolone in tablets is discussed.Some new chemistry of 16a-hydroxylated steroids is reviewed. RIAMCINOLONE (9a -fluoro -11/3,16a,lia,21tetrahydroxy-l,4-pregnadiene-3,20-dione) is a new potent corticosteroid of clinical importance (1-3). Triamcinolone is currently marketed in this country as the alcohol, although the IGa,21diacetate has been tested clinically (4). Characterization of the hormone has been limited to brief accounts in the chemical journals (5-i) and in the patent literature (8). A more detailed characterization of both triamcinolone and triamcinolone diacetate is the subject of this report. in the preparation of triamcinolone and triamcinolone diacetate standards. Ultraviolet absorption spectra were obtained under the direction of Mr. Walter Muller, infrared spectra were kindly supplied by Mr. William Fulmor.

16α-Hydroxy Steroids

“…In addition, a third component was at times present. This was suggested to be the isomer of 23, 16a-dihydroxy-9afluorohydrocortisone analogous to that found previously for 9a-fluoro , 16a-hydroxyhydrocortisone (Smith et al, 1960a). With the Waksman strain, 2g-hydroxylated products were only rarely found.…”

Detection and characterization of triamcinolone acetonide metabolites in human urine by liquid chromatography/tandem mass spectrometry after intramuscular administration

“…Compound M‐X was also detected in methanolic solutions of T; however, it was not detected in an acetonitrile solution, indicating that it is also a degradation product of T. The compound was not detected in urines spiked with T and, therefore, no degradation occurs during the extraction procedure. An isomerization to generate a six‐membered D‐ring in methanol and other conditions have been described for T, and the structure of the product was established by NMR as 9‐fluoro‐11β,16β,17α‐trihydroxy‐17‐hydroxymethyl‐D‐homoandrosta‐1,4‐diene‐3,17α‐dione (Fig. ) .…”

Use of liquid chromatography/tandem mass spectrometric molecular fingerprinting for the rapid structural identification of pharmaceutical impurities

“…6(D). The latter species is a degradant resulting from an isomerization process known as D‐homoannular ring expansion of the core steroid structure 12. Hence, based on the MS 3 fingerprint, BSP Isomer 3 was identified as 9‐fluoro‐11 β ,17a β ‐dihydroxy‐17a‐[(phosphonooxy)methyl]‐D‐homoandrosta‐1,4‐diene‐3,17a‐dione, formed via pathway (a) of a plausible D‐homoannular ring expansion of BSP in the solid state (Scheme ).…”