Abstract
A rapid, precise and reliable LC-MS/MS method has been developed for the identification and characterization of stressed degradation products of Tetrabenazine. Tetrabenazine is a drug, for the symptomatic treatment of hyperkinetic movement disorder. Tetrabenazine works mainly as a VMAT inhibitor. It promotes the early metabolic degradation of monoamines, in particular the neurotransmitter dopamine. Tetrabenazine was subjected to hydrolysis acidic, alkaline, neutral peroxidation, light and thermal stress conditions as per ICH-specified conditions. The drug showed degradation under peroxidation, thermal, acid and base hydrolysis stress conditions. However, it was stable to neutral stress conditions and light degradation. A total of 4 degradation products were observed and the chromatographic separation of the drug and its degradation products were achieved on Inertsil ODS-3V 150 mm × 4.6 mm, i.d., 5 μm column using 0.01 M ammonium acetate and ACN in the ratio of 640:360 as mobile phase-A and 900:100 ratio of ACN:Water as mobile phase –B. The degradation products were characterized by LC–MS/MS and its fragmentation pathways were proposed. Probable possible structures were drawn based on parent and daughter molecular ions.
Highlights
Tetrabenazine TBZ [1,2,3,4] a catecholamine-depleting agent initially developed for the treatment of schizophrenia, when tested for other indications, has proven to be more useful for the treatment of a variety of hyperkinetic movement disorders
Aqueous ammonium acetate buffer 0.01 M as Mobile phase A and Acetonitrile:water 40:60%, v/v in gradient elution mode and Inertsil ODS-3V 150 mm × 4.6 mm, i.d., 5 μm column was used for successful separation of Tetrabenazine and its degradation products
The degradation behaviour of Tetrabenazine under hydrolysis acid, base and neutral, oxidation conditions was carried out according to ICH guidelines
Summary
Tetrabenazine TBZ [1,2,3,4] a catecholamine-depleting agent initially developed for the treatment of schizophrenia, when tested for other indications, has proven to be more useful for the treatment of a variety of hyperkinetic movement disorders. Its chemical name is SS, RR3- isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-pyrido [2,1-a isoquinoline-2-one (Figure 1). The hyperkinetic movement disorders include neurological diseases characterized by abnormal involuntary movements such as chorea associated with Huntington’s disease, tics in Received December 30, 2015; Accepted December 31, 2016; Published January 08, 2016. Chem Sci J ISSN: 2150-3494 CSJ, an open access journal
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