Mechanism driven structural elucidation of forced degradation products from hydrocortisone in solution.
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.
Analytical Development, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States. Electronic address: fzhang1@its.jnj.com.
Fa
F
Zhang
Analytical Development, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States.
Jay
J
Zhou
Analytical Development, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States.
Yiqun
Y
Shi
Analytical Development, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States.
Panagiotis
P
Tavlarakis
Analytical Development, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States.
Kenneth
K
Karaisz
D000893:Anti-Inflammatory Agents / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D004355:Drug Stability; D006854:Hydrocortisone / Q000032:analysis*; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D019999:Pharmaceutical Solutions / Q000032:analysis; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D014867:Water
D000893:Anti-Inflammatory Agents; D019999:Pharmaceutical Solutions; D014867:Water; D006854:Hydrocortisone
Degradation; HPLC–MS; Hydrocortisone; Mechanism; NMR