Structural elucidation of two photolytic degradation products of tetrabenazine.
Structural elucidation of two photolytic degradation products of tetrabenazine.
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DOI：
10.1016/j.jpba.2013.12.032
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发表时间：
2014-03
影响因子：
3.4
通讯作者：
Zouaoui Bourezg;N. Cartiser;L. Ettouati;J. Guillon;Aline Lacoudre;N. Pinaud;M. Le Borgne;H. Fessi
中科院分区：
文献类型：
--
作者：
Zouaoui Bourezg;N. Cartiser;L. Ettouati;J. Guillon;Aline Lacoudre;N. Pinaud;M. Le Borgne;H. Fessi
丁苯那嗪（tetrabenazine， TBZ）是一种多巴胺消耗剂，用于亨廷顿舞蹈病相关的舞蹈病和多动运动障碍的对症治疗，在溶液配方研究中，观察到储存时强烈变色。我们通过强制降解研究来研究这种物理化学行为。仅在TBZ溶液的Suntest®光照射下观察到泛黄。LC-MS（液相色谱耦合质谱仪检测）分析表明，1,11b-去二氢四苯那嗪（DTBZ）和1,3,4,11b-去四氢四苯那嗪（TTBZ）是光暴露TBZ样品的主要杂质。研究了DTBZ和TTBZ·HCl的合成，并用核磁共振和x射线晶体学对其结构进行了完整的测定。它们在LC-MS中与在光暴露TBZ样品中发现的极性杂质相同。然而，即使这些太赫兹降解产物与太赫兹溶液的变色有关，也没有证据表明它们是直接导致变色的原因。
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.