Gas chromatography-mass spectrometry assay method for the therapeutic drug monitoring of the antiepileptic drug tiagabine.
A gas chromatography-mass spectrometry assay method suitable for the therapeutic drug monitoring of the antiepileptic drug tiagabine is described. Tiagabine and its desmethylated analogue used as internal standard were first extracted from serum by liquid-liquid extraction using an ethyl ether-isobutanol 98:2 mixture. Tiagabine and the internal standard were then methylated in the organic phase in presence of methanol by means of a safe and stable diazomethane derivative. After evaporation, the reconstituted extracts were chromatographed on a crosslinked phenyl methyl siloxane capillary column and detected by mass fragmentometry at m/z = 156. No other antiepileptic drug possibly administrated in polytherapy and no metabolite were found to interfere in the assay. The limit of quantification was 5 ng/ml. The precision and the accuracy were found to be suitable for the therapeutic drug monitoring of tiagabine.
Chollet
D F
DF
Covance Central Laboratory Services SA, Meyrin/Geneva, Switzerland. daniel.chollet@covance.com
Castella
E
E
Goumaz
L
L
Anderegg
G
G
D000927:Anticonvulsants / Q000032:analysis / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D009557:Nipecotic Acids / Q000032:analysis / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D000078308:Tiagabine
D000927:Anticonvulsants; D009557:Nipecotic Acids; D000078308:Tiagabine