Degradation of vitamin D3 in a stressed formulation: the identification of esters of vitamin D3 formed by a transesterification with triglycerides.
Four unknown degradants in the LC-UV profile of a stressed experimental tablet formulation that contains vitamin D3 have been identified by a combination of Ag+-cationization electrospray ionization (ESI) LC/MS and atmospheric pressure chemical ionization (APCI) LC/MS/MS. The peaks elute in the method chromatography in two pairs of two peaks. The first pair of peaks has m/z 511 while the second pair has m/z 539. The major, first peak of each set of peaks corresponds to the octanoate and decanoate ester of vitamin D3, respectively. These are formed by a transesterification with the two major fatty acid components (octanoate and decanoate) of the triglycerides present in the formulation. The formation of two degradation products with each fatty acid is due to the presence of both vitamin D3 (major component) and the isomeric pre-vitamin D3 (minor component) in the stressed formulation.
Ballard
John M
JM
Pharmaceutical Research and Development, Merck Research Laboratories, P.O. Box 4, West Point, PA 19486, United States.
Zhu
Limin
L
Nelson
Eric D
ED
Seburg
Randal A
RA
D002626:Chemistry, Pharmaceutical; D002762:Cholecalciferol / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004952:Esters / Q000032:analysis; D006358:Hot Temperature; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets; D014280:Triglycerides / Q000032:analysis
D004952:Esters; D013607:Tablets; D014280:Triglycerides; D002762:Cholecalciferol