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Mechanism driven structural elucidation of forced degradation products from hydrocortisone in solution
Fa Zhang1, Jay Zhou1, Yiqun Shi1
1Analytical Development, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States.
Abstract:
Hydrocortisone degradation products 1, 2, 3, and 4 along with hemiacetal derivatives 5, 6, 7, and 8 were observed through stressed hydrocortisone in solution. Their structures were identified based on HPLC-UV, HPLC-MS, and HPLC-HRMS (high resolution/high accuracy mass spectrometry) analyses as well as reaction mechanistic investigation and synthesis for structural confirmation. 1 and 2 are a pair of E/Z isomers and they were generated through acid catalyzed tautomerization/dehydration of hydrocortisone. Incorporation of water to 1 and 2 resulted in the formation of 3. We also discovered new degradation product 4 which was converted from 3 by oxidation. The degradation products were synthesized by stressing hydrocortisone under the optimized conditions and their structures were characterized by NMR ((1)H/(13)C, COSY, HMBC, HSQC, NOESY) and HRMS analyses. The degradation pathway of hydrocortisone is postulated.
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