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Quantitative determination of gabapentin and vigabatrin by HPLC in the serum of patients with epilepsy

Introduction: Gabapentin (Gabalept_, Katena_, Neurontin_) and vigabatrin (Sabril_) are chemical compounds that represent new-generation antiepileptic drugs. Gabapentin (GBP) has been designed as a structural analogue of GABA, and has been demonstrated to increase GABA concentration. The mechanism of action is related to events modulated through its interaction with a receptor thought to be associated with L-system amino acid carrier protein. Vigabatrin (VGB) is a synthetic GABA derivate. It is an enzyme-activated, irreversible inhibitor of GABA transaminase that resulted from a systematic search into possible ways of increasing GABAergic inhibition through interference with GABA metabolism. GBP and VGA are eliminated renally completely unchanged and the pharmacokinetic varability is more predictable. Material and Method: A simple method was developed for the routine clinical monitoring of the antiepileptic drugs GBP and VGB in the serum of patients with epilepsy using high- performance liqid chromatography (HPLC) with fluorescence detector set at λexc=235 nm and λem=435 nm. After protein precipitation with acetonitril compounds are pre-column derivatized by o-phthaldehyde (OPA). Separations were carried out at 28° C on Nucleodur C18 100-5 column (dp=5_m) from Macherey Nagel. The mobile phase was isocratic, consisting of 0.02 M phosphoric acid and acetonitril (45:55, v/v) with flow-rate 0.6 ml/min. Results: The method was fully validated and linear calibration curves were obtained in the concentration ranges from 21.9 to 146.0 _mol/L for GBP and 57.9 to 386.5 _g/ml for VGB. The limit of detection (LOD) was 0.047 _mol/L for GBP, and 1.724 _mol/L for VGB. The limit of quatitation (LOQ) was 0.123 _mol/L for GBP, and 3.718 _mol/L for VGB. The within-day precision expressed as relative standard deviations (RSD) for two different concentration levels (n = 10) were 10% for both compounds, and day-to-day RSD at two different concentration levels during 3 separate days were 5% for GBA, and 10 % for VGB. Conclusion: The described method was simple, fast, highly sensitive and reproducible, while endogenous compounds did not interfere with the assay. It was used for simultaneous analysis of both antepileptic drugs in therapeutic drug monitoring.

gabapentin; vigabatrin; HPLC; epilepsy

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