Identification of tiagabine degradation products using liquid chromatography with electrospray ionization multistage mass spectrometry and ultra-performance liquid chromatography/high-resolution mass spectrometry.

Abstract

RATIONALE:

Tiagabine hydrochloride monohydrate drug substance (TGB) is an antiepileptic agent effective in the treatment of seizure disorders. The stability of TGB was studied and its degradation products were identified for the first time.

METHODS:

TGB was heated in the presence of H(2)O(2). Degradation products were analyzed by liquid chromatography coupled to electrospray ionization multistage mass spectrometry (LC/ESI-MS(n)) and high-resolution mass spectrometry (HR-MS).

RESULTS:

This study showed that TGB was degraded by oxidative pathways involving attack of oxygen at different centers but mainly at the double bond of the molecule. The oxidative cascade reactions initiated by the epoxidation of the double bond of tiagabine led to dihydroxy, ketohydroxy and ketone derivatives as well as bisthiophene ketone.

CONCLUSIONS:

Nine degradation products of TGB were identified. Some diagnostic MS/MS product ions, characteristic of the piperidine or thiophene moiety, were highlighted.

• Authors: Marie Hubert-Roux, Mohamed Skiba, Abdussalam Sughir, Malika Lahiani-Skiba, Fabienne Olivier-Chanu, Vincent Levacher, Catherine M Lange
• Journal: Rapid communications in mass spectrometry : RCM (Rapid Commun Mass Spectrom) Vol. 26 Issue 3 Pg. 287-96 (Feb 15 2012) ISSN: 1097-0231 [Electronic] England
• PMID: 22223315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 John Wiley & Sons, Ltd.

Chemical References

• Anticonvulsants
• Ions
• Nipecotic Acids
• Hydrogen Peroxide
• Tiagabine

Topics

• Anticonvulsants (chemistry)
• Chemical Phenomena
• Chromatography, High Pressure Liquid (methods)
• Drug Stability
• Hydrogen Peroxide (chemistry)
• Ions (chemistry)
• Nipecotic Acids (chemistry)
• Spectrometry, Mass, Electrospray Ionization (methods)
• Tandem Mass Spectrometry (methods)
• Tiagabine