11β,16α,17α,21-Tetrahydroxypregna-1,4-diene-3,20-dione

• CAT Number: R003898
• CAS Number: 13951-70-7
• Molecular Formula: C₂₁H₂₈O₆
• Molecular Weight: 376.44
• Purity: ≥95%
• Storage: Store at RT
• IUPAC Name: (8S,9S,10R,11S,13S,14S,16R,17S)-11,16,17-trihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-one
• InChI: InChI=1S/C21H28O6/c1-19-6-5-12(23)7-11(19)3-4-13-14-8-16(25)21(27,17(26)10-22)20(14,2)9-15(24)18(13)19/h5-7,13-16,18,22,24-25,27H,3-4,8-10H2,1-2H3/t13-,14-,15-,16+,18+,19-,20-,21-/m0/s1
• InChIKey: SEKYBDYVXDAYPY-ILNISADRSA-N
• SMILES: CC12CC(C3C(C1CC(C2(C(=O)CO)O)O)CCC4=CC(=O)C=CC34C)O

16alpha-Hydroxyprednisolone(CAS: 13951-70-7) is a C21 steroid that is obtained by hydroxylation of pregnenolone at the C17a position. This step is performed by the mitochondrial cytochrome P450 enzyme 17a-hydroxylase (CYP17A1) that is present in the adrenal and gonads. Peak levels are reached in humans at the end of puberty and then decline. High levels are also achieved during pregnancy. 16alpha-Hydroxyprednisolone is also an advanced intermediate in the synthesis of various corticosteroids such as budesonide and ciclesonide.

Reference

[1]. Molecules. 2020 Oct 23;25(21):4912. doi: 10.3390/molecules25214912.
Biotechnological Transformation of Hydrocortisone into 16α-Hydroxyprednisolone by Coupling Arthrobacter simplex and Streptomyces roseochromogenes.
Restaino OF(1), Barbuto Ferraiuolo S(1), Perna A(1), Cammarota M(1), Borzacchiello MG(1), Fiorentino A(2), Schiraldi C(1).
Author information: (1)Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138 Naples, Italy. (2)Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Via Vivaldi 43, 81100 Caserta, Italy.
16α-Hydroxyprednisolone, an anti-inflammatory drug, could be potentially obtained from hydrocortisone bioconversion by combining a 1,2-dehydrogenation reaction performed by Arthrobacter simplexATCC31652 with a 16α-hydroxylation reaction by Streptomyces roseochromogenes ATCC13400. In this study we tested, for the first time, potential approaches to couple the two reactions using similar pH and temperature conditions for hydrocortisone bioconversion by the two strains. The A. simplex capability to 1,2-dehydrogenate the 16α-hydroxyhydrocortisone, the product of S. roseochromogenes transformation of hydrocortisone, and vice versa the capability of S. roseochromogenes to 16α-hydroxylate the prednisolone were assessed. Bioconversions were studied in shake flasks and strain morphology changes were observed by SEM. Whole cell experiments were set up to perform the two reactions in a sequential mode in alternate order or contemporarily at diverse temperature conditions. A. simplex catalyzed either the dehydrogenation of hydrocortisone into prednisolone efficiently or of 16α-hydroxyhydrocortisone into 16α-hydroxyprednisolone in 24 h (up to 93.9%). Surprisingly S. roseochromogenes partially converted prednisolone back to hydrocortisone. A 68.8% maximum of 16α-hydroxyprednisolone was obtained in 120-h bioconversion by coupling whole cells of the two strains at pH 6.0 and 26 °C. High bioconversion of hydrocortisone into 16α-hydroxyprednisolone was obtained for the first time by coupling A. simplex and S. roseochromogenes.
DOI: 10.3390/molecules25214912 PMCID: PMC7660607 PMID: 33114231 [Indexed for MEDLINE]

[2]. MethodsX. 2016 Feb 24;3:139-43. doi: 10.1016/j.mex.2016.02.004. eCollection 2016.
An LC-MS/MS method for the determination of budesonide and 16α-hydroxyprednisolone in dog plasma.
Gazzotti T(1), Barbarossa A(1), Zironi E(1), Roncada P(1), Pietra M(1), Pagliuca G(1).
Author information: (1)Department of Veterinary Medical Sciences – University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano dell'Emilia (BO), Italy.
Although budesonide is frequently used in veterinary medicine for the treatment of canine respiratory and bowel inflammatory diseases, knowledge is lacking regarding its kinetics in this species. We developed and validated a liquid chromatography-tandem mass spectrometry method for the determination of budesonide and its metabolite 16α-hydroxyprednisolone in dog plasma. The analytes were extracted by solid phase extraction and analysis was performed by high performance liquid chromatography-tandem mass spectrometry, with positive electrospray ionization.•This method allows budesonide and one of its main metabolites to be simultaneously quantified in dog plasma at fairly low concentrations.•The proposed protocol is very easy and fast to execute, without compromising analytical performances.•A small amount (0.5 mL) of plasma is required, making this approach suitable for pharmacokinetic studies also in small sized dogs.
DOI: 10.1016/j.mex.2016.02.004 PMCID: PMC4929248 PMID: 27408833

[3]. Biomed Chromatogr. 2003 Mar-Apr;17(2-3):158-64. doi: 10.1002/bmc.233.
Simultaneous quantification of budesonide and its two metabolites, 6beta-hydroxybudesonide and 16alpha-hydroxyprednisolone, in human plasma by liquid chromatography negative electrospray ionization tandem mass spectrometry.
Wang Y(1), Tang Y, Moellmann H, Hochhaus G.
Author information: (1)Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
A sensitive, rapid and selective liquid chromatography negative electrospray ionization tandem mass spectrometry [LC-(-)ESI-MS-MS] method has been developed and validated for the simultaneous quantification of budesonide (BUD) and its major metabolites, 6beta-hydroxybudesonide (OH-BUD) and 16alpha-hydroxyprednisolone (OH-PRED) in human plasma. The method was validated over a linear range from 0.1 to 10 ng/mL for all three analytes using a solid-phase extraction procedure with 9-fluoro-hydrocortisone as the internal standard. The between-day and within-day coefficients of variation for all compounds were < or =20% at the concentrations of lower limit of quantification and < or =15% at other quality control concentrations. The utility of this assay was demonstrated by monitoring BUD, OH-BUD and OH-PRED plasma concentrations in one healthy subject for 24 h following a 3 mg oral dose of budesonide, administered as a pH modified release capsule (Budenofalk) to healthy volunteers.
DOI: 10.1002/bmc.233 PMID: 12717805 [Indexed for MEDLINE]

[4]. Acta Endocrinol (Copenh). 1969 Jul;61(3):477-82. doi: 10.1530/acta.0.0610477.
The relative effects of cortisone and triamcinolone (9alpha-fluoro-16alpha-hydroxyprednisolone) on the urinary excretion of trsin inhibitor in man.
Faarvang HJ, Lauritsen OS.
DOI: 10.1530/acta.0.0610477 PMID: 5820058 [Indexed for MEDLINE]

[5]. J Pharm Biomed Anal. 2006 Oct 11;42(4):474-9. doi: 10.1016/j.jpba.2006.05.016. Epub 2006 Jul 12.
Detection of budesonide in human urine after inhalation by liquid chromatography-mass spectrometry.
Deventer K(1), Mikulcíková P, Van Hoecke H, Van Eenoo P, Delbeke FT.
Author information: (1)Doping Control Laboratory (DoCoLab), Ghent University, UGent, Technologiepark 30B, B-9052 Zwijnaarde, Belgium.
Budesonide, a corticosteroid frequently used in the treatment of asthma, is most often administered via inhalation. Its use in sports is allowed when medically necessary. A fast, sensitive and accurate LC-MS method was developed and validated for the quantification of budesonide and its major metabolite 16alpha-hydroxyprednisolone in urine samples after inhalation of a metered dose (Pulmicort-Turbohaler 200). Sample preparation consists of an alkaline liquid-liquid extraction with ethyl acetate. Analysis was performed using liquid chromatography-tandem mass spectrometry with electrospray ionization (ESI). The method was linear in the range of 5-100 and 0.5-10ng/mL for 16alpha-hydroxyprednisolone and budesonide, respectively. The limits of quantification were 5ng/ml for 16alpha-hydroxyprednisolone and 0.5ng/mL for budesonide. The accuracy ranged from 2.2 to 3.5% for 16alpha-hydroxyprednisolone and from 0.8 to 16.4% for budesonide. After administration of 200microg of budesonide to five healthy volunteers budesonide could not be detected in any urine sample whereas 16alpha-hydroxyprednisolone was detectable up to 12h post-administration.
DOI: 10.1016/j.jpba.2006.05.016 PMID: 16842962 [Indexed for MEDLINE]