Identification of the secondary degradates of L-648,548 in an animal health formulation.
L-648,548 is a semisynthetic analog of avermectin. During stability investigations of this compound in an animal health formulation, two new degradates were discovered. These degradates (L-648,548 phenol and its 8,9-Z isomer) were identified as the reaction products of 5-oxo-L-648,548 formed by oxidation of L-648,548. Addition of base to the reaction medium containing 5-oxo-L-648,548 was found to catalyze the formation of L-648,548 phenol via a postulated dehydration by an E1cb elimination followed by the rapid tautomerization of the C5 carbonyl. Photolysis of L-648,548 phenol with visible light (including ambient laboratory lighting) was found to readily produce 8,9-Z-L-648,548 phenol. This transformation was confirmed to be exclusively a photoinduced process.
Wang
Q
Q
Merck Research Laboratories, West Point, PA 19486, USA.
Stong
J D
JD
Demontigny
P
P
Ballard
J M
JM
Murphy
J S
JS
Shim
J S
JS
Faulkner
A J
AJ
D004340:Drug Contamination; D004355:Drug Stability; D007306:Insecticides / Q000737:chemistry*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry
D007306:Insecticides; C100820:L 648548; D007559:Ivermectin