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Updated: May 3, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Structural elucidation of two photolytic degradation products of tetrabenazine
Zouaoui Bourezg1, Nathalie Cartiser2, Laurent Ettouati2
1Université de Lyon, Université Lyon 1, LAGEP, UMR 5007, CNRS, CPE, 43 bd du 11 novembre, 69100 Villeurbanne, France.
Abstract:
During solution formulation study of tetrabenazine (TBZ), a dopamine depleting agent, used in chorea associated with Huntington's disease and symptomatic treatment of hyperkinetic movement disorder it was observed a strong discoloration upon storage. We investigated this physico-chemical behavior by implementing forced degradation studies. It was observed yellowing only under Suntest(®) light exposure of TBZ solution. LC-MS (liquid chromatography coupled to mass spectrometer detection) analysis of light exposed TBZ samples allowed us to propose 1,11b-dedihydrotetrabenazine (DTBZ) and 1,3,4,11b-detetrahydrotetrabenazine (TTBZ) as the main TBZ impurities. Synthesis and complete structural determination of DTBZ and TTBZ·HCl by NMR and X-ray crystallography were carried out. They were identical in LC-MS with polar impurities found in light exposed TBZ samples. However, even if these TBZ degradation products are correlated with discoloration of TBZ solution there is no evidence they are directly responsible of it.
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