Vigabatrin (4-amino-5-hexenoic acid) is an antiepileptic drug whose probable mechanism of action is the inhibition of GABA transaminase, which leads to reduced neuronal activity as a consequence of the increased GABA concentration. The drug is orally administered at doses ranging from 1.5 to 4 g/day and the commonly reported therapeutic plasma concentrations are between 20 and 60 g/mL. Side effects such as fatigue, drowsiness, headache and weight gain are frequent, but also irreversible visual field defects may occur in long-term treated patients. In order to accurately and selectively determine Vigabatrin plasma levels in patients under treatment with the drug, a capillary electrophoretic method with laser-induced fluorescence (LIF) detection (laser wavelength 488 nm) has been developed. Sample pre-treatment is based on SPE with mixed-mode lipophilic-strong cation exchange (MCX) cartridges, that allowed the removal of interference and good extraction yield (>96%). Since the analyte is neither fluorescent nor UV-active, a fast (30 min) derivatisation procedure with 6-carboxyfluorescein-N-succinimidyl ester has been developed, allowing the selective determination of Vigabatrin by LIF. The BGE is composed of a pH 9 borate buffer, supplemented with N-methylglucamine in order to separate the analyte from labelling agent excess peaks. Good linearity was found over the 10-120 µg/mL concentration range. The method shows good precision (RSD%< 6.7). Finally, the method has been applied to the determination of the analyte in real plasma samples from patients undergoing treatment with Vigabatrin; accuracy assays gave all results between 97.0 and 101.6%. Thus, the method seems to be suitable for the therapeutic drug monitoring of Vigabatrin in epileptic patients.

Application of capillary electrophoresis coupled to laser-induced fluorescence detection for the selective determination of vigabatrin in human plasma

MUSENGA, ALESSANDRO;MOHAMED, SUSAN;MANDRIOLI, ROBERTO;RAGGI, MARIA AUGUSTA
2007

Abstract

Vigabatrin (4-amino-5-hexenoic acid) is an antiepileptic drug whose probable mechanism of action is the inhibition of GABA transaminase, which leads to reduced neuronal activity as a consequence of the increased GABA concentration. The drug is orally administered at doses ranging from 1.5 to 4 g/day and the commonly reported therapeutic plasma concentrations are between 20 and 60 g/mL. Side effects such as fatigue, drowsiness, headache and weight gain are frequent, but also irreversible visual field defects may occur in long-term treated patients. In order to accurately and selectively determine Vigabatrin plasma levels in patients under treatment with the drug, a capillary electrophoretic method with laser-induced fluorescence (LIF) detection (laser wavelength 488 nm) has been developed. Sample pre-treatment is based on SPE with mixed-mode lipophilic-strong cation exchange (MCX) cartridges, that allowed the removal of interference and good extraction yield (>96%). Since the analyte is neither fluorescent nor UV-active, a fast (30 min) derivatisation procedure with 6-carboxyfluorescein-N-succinimidyl ester has been developed, allowing the selective determination of Vigabatrin by LIF. The BGE is composed of a pH 9 borate buffer, supplemented with N-methylglucamine in order to separate the analyte from labelling agent excess peaks. Good linearity was found over the 10-120 µg/mL concentration range. The method shows good precision (RSD%< 6.7). Finally, the method has been applied to the determination of the analyte in real plasma samples from patients undergoing treatment with Vigabatrin; accuracy assays gave all results between 97.0 and 101.6%. Thus, the method seems to be suitable for the therapeutic drug monitoring of Vigabatrin in epileptic patients.
Proceedings of RDPA 2007, 12th Meeting on Recent Developments in Pharmaceutical Analysis
90
90
A. Musenga; S. Mohamed; R. Mandrioli; E. Kenndler; C. Bartoletti; M.A. Raggi
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/50252
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact