Degradation chemistry of a Vitamin D analogue (ecalcidene) investigated by HPLC-MS, HPLC-NMR and chemical derivatization.
Ecalcidene (1-[(1alpha,3beta,5Z,7E,20S)-1,3-dihydroxy-24-oxo-9,10-secochola-5,7,10(19)-trien-24-yl]-piperidine) is a new 1-hydroxyvitamin D analogue. In this report, the thermal degradation, acid induced degradation and iodine induced degradation of ecalcidene were investigated using HPLC-MS, HPLC-NMR and chemical derivatization. In solution ecalcidene was thermally and reversibly transformed to a pre-Vitamin D type isomer 1 which subsequently produced the dehydrated pyrocalciferol and isopyrocalciferol type isomers 2 and 3 by cyclization and dehydration at elevated temperatures. Acidic conditions resulted in the formation of a novel C9-hydroxylated isomer 4 of ecalcidene, possibly via a tachysterol type intermediate, followed by the acid facilitated nucleophilic addition of water. In the presence of iodine, cis/trans isomerization of both ecalcidene and its pre-Vitamin D type isomer 1 occurred. The results may shed light on the stability and metabolism of ecalcidene, provide useful information for its potential pharmaceutical development, and enrich the knowledge of Vitamin D chemistry.
Zhang
Fa
F
Analytical and Chemical Development, Drug Development Operations, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ 08558, USA. fzhang1@cpcus.jnj.com
Nunes
Mathews
M
Segmuller
Brigitte
B
Dunphy
Richard
R
Hesse
Robert Henry
RH
Setty
Sundara Katugam Srinivasetty
SK
D050071:Bone Density Conservation Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007455:Iodine; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000737:chemistry
D050071:Bone Density Conservation Agents; D014807:Vitamin D; C519578:ecalcidene; D007455:Iodine