Identification of a new by-product detected in metoprolol tartrate.
A new impurity has been found in some batches of metoprolol tartrate. As the amount exceeded 0.1% it was of interest to deduce the structure. Techniques involved in solving the problem were LC, LC-MS and GC-MS. The LC systems showed that the impurity and metoprolol behaved differently to modifications of the mobile phase, indicating that there were differences in the functional groups. LC-MS was used to determine the molecular weight, which was 74 mass units higher than metoprolol. A hydrogen-deuterium shift technique using micro column LC-MS gave the information that three hydrogen atoms were bound to heteroatoms, i.e. one more than in metoprolol. This led to the conclusion that the impurity had three extra carbon and two extra oxygen atoms. It was supposedly a by-product in the synthesis. Knowledge of the synthesis steps for beta-receptor blocking drugs suggested three possible structures. Two were independently synthesized and one of these was found to be identical to the impurity.
Erickson
M
M
Astra Hässle AB, Department of Analytical Chemistry, Mölndal, Sweden.
Karlsson
K E
KE
Lamm
B
B
Larsson
S
S
Svensson
L A
LA
Vessman
J
J
D002853:Chromatography, Liquid; D004340:Drug Contamination; D008401:Gas Chromatography-Mass Spectrometry; D013058:Mass Spectrometry; D008790:Metoprolol / Q000032:analysis*; D013056:Spectrophotometry, Ultraviolet
D008790:Metoprolol