Identification of tiagabine degradation products using liquid chromatography with electrospray ionization multistage mass spectrometry and ultra-performance liquid chromatography/high-resolution mass spectrometry.
BACKGROUND
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.
Université de Rouen, CNRS-UMR6014, Rue tesnières, 76821, Mont-Saint-Aignan cedex, France. marie.hubert@univ-rouen.fr
Marie
M
Hubert-Roux
Mohamed
M
Skiba
Abdussalam
A
Sughir
Malika
M
Lahiani-Skiba
Fabienne
F
Olivier-Chanu
Vincent
V
Levacher
Catherine M
CM
Lange
D000927:Anticonvulsants / Q000737:chemistry; D055598:Chemical Phenomena; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006861:Hydrogen Peroxide / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D009557:Nipecotic Acids / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000078308:Tiagabine
D000927:Anticonvulsants; D007477:Ions; D009557:Nipecotic Acids; D006861:Hydrogen Peroxide; D000078308:Tiagabine