Forced degradation of betamethasone sodium phosphate under solid state: Formation, characterization, and mechanistic study of all four 17,20-diastereomers of betamethasone 17-deoxy-20-hydroxy-21-oic acid

Journal of Pharmaceutical Sciences

Volumn 98, Issue 3, 2009, Pages 894-904

  Li, Min ^a   Wang, Xin ^a   Chen, Bin ^a   Chan, Tze Ming ^a   Rustum, Abu ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Betamethasone 17 deoxy 20 hydroxy 21 oic acid; Betamethasone enol aldehyde; Corticosteroids; Degradation; LC MS

Indexed keywords

BETAMETHASONE; BETAMETHASONE 17ALPHA DEOXY 20 HYDROXY 21 OIC ACID; BETAMETHASONE 17BETA DEOXY 20 HYDROXY 21 OIC ACID; BETAMETHASONE ENOL ALDEHYDE; BETAMETHASONE SODIUM PHOSPHATE; UNCLASSIFIED DRUG;

ARTICLE; CANNIZZARO REACTION; DIASTEREOISOMER; DRUG DEGRADATION; DRUG STRUCTURE; HEAT STRESS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDRATION; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE; PHYSICAL CHEMISTRY;

EID: 62849108423     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.21477     Document Type: Article

References (9)

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5. Arthur KE, Wolff J-C, Carrier DJ. 2004. Analysis of betamethasone, dexamethasone and related compounds by liquid chromatography/electrospray mass spectrometry. Rapid Commun. Mass Spectrom 18:678-684.
6. The four degradants 2a, 2b, 3a, and 3b correspond to the peaks eluting at retention times of 11.5, 13.3, 14.6, and 12.8 minutes (Fig. 1), respectively.
7. Lewbart ML, Mattox VR. 1963. Conversion of Steroid-17-al Glyoxals to Epimeric Glycolic Esters. J Org Chem 28:1779-1786.
8. Both the E- and Z-isomers of betamethasone enol aldehyde were found to undergo the intramolecular Cannizzaro reaction although the distribution of the four diastereomers were slightly different. Only the reaction of the E-isomer is shown.
9. n studies, which appeared to be caused partly by different instruments used and by the presence of THF in the mobile phase. THF is a strong organic modifier and any small variation in its concentration tends to give large impact to retention times.