Identification and structural elucidation of an oxidation product generated during stability studies of Cabergoline drug product.

Cabergoline is a dopamine agonist with applications as anti-Parkinson drug and prolactin inhibitor. The cabergoline drug product Laktostop® 50 µg/mL is used in veterinary medicine for lactation suppression in cats and dogs e.g. during false pregnancy. Recently, during ongoing HPLC stability testing of Laktostop® 50 µg/mL a new oxidation product of Cabergoline was identified. A synthesis starting from Cabergoline was developed, followed by full characterization of the unknown impurity. Preliminary HPLC and LC-MS analyses indicated the unknown impurity as mono-oxygenated product of Cabergoline (Cabergoline N-oxide) that is presumably formed with oxygen by a radical mechanism. Thus, Cabergoline was treated with oxidizing agents such as m-chloroperoxybenzoic acid to afford the desired Cabergoline-N-oxide as a byproduct. After isolation by column chromatography, NMR and LC-MS-MS studies provided evidence that oxidation occurred at the N-allyl nitrogen of Cabergoline to form Cabergoline-N-oxide. © 1905 Elsevier Science. All rights reserved.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships: T. Lechel, R. Silva Otero, A. Rutkowski, D. Matzkow, J. Zart and T. Hartmann are employed at Chemisch-pharmazeutisches Labor, Rolf Sachse GmbH (CPL). D. Hochhuth is employed at CP-Pharma Handelsgesellschaft mbH which financed the project. However, no one at CPL or CP-Pharma had an influence on the results presented in the manuscript. A. Springer collaborated with CPL for LC-MS analysis of cabergoline N-oxide 5. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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