title: Simultaneous determination of gabapentin, pregabalin, vigabatrin, and topiramate in plasma by HPLC with fluorescence detection.
abstract: Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) has been recognized as a useful tool in management of epilepsy. We developed a simple analytical method for simultaneous determination of four second generation AEDs, including gabapentin (GBP), pregabalin (PGB), vigabatrin (VGB), and topiramate (TOP). Analytes were extracted from human plasma using universal solid phase extraction, derivatized with 4-chloro-7-nitrobenzofurazan (NBD-Cl) and analyzed by HPLC with fluorescence detection. Using mass spectrometry we confirmed that NBD-Cl reacts with sulfamate group of TOP similarly as with amine group of the other three analytes. The method is linear (r(2)>0.998) across investigated analytical ranges (0.375-30.0μg/mL for GBP, PGB, and VGB; 0.50-20.0μg/mL for TOP). Intraday and interday precision do not exceed 9.40%. The accuracy is from 95.6% to 106%. The recovery is higher than 80.6%, and the lower limit of quantification is at least 0.5μg/mL. The method is selective and robust. For TOP determination the method was compared to a previously published method and the results obtained by the two methods were in good agreement. The developed method is suitable for routine TDM.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
authors.forename: Boštjan
authors.initials: B
authors.lastname: Martinc
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
authors.forename: Robert
authors.initials: R
authors.lastname: Roškar
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
authors.forename: Iztok
authors.initials: I
authors.lastname: Grabnar
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia. Electronic address: tomaz.vovk@ffa.uni-lj.si.
authors.forename: Tomaž
authors.initials: T
authors.lastname: Vovk
mesh_terms: D000588:Amines / Q000097:blood*; D000927:Anticonvulsants / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003509:Cyclohexanecarboxylic Acids / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods; D005453:Fluorescence; D005632:Fructose / Q000031:analogs & derivatives* / Q000097:blood; D000077206:Gabapentin; D006801:Humans; D057230:Limit of Detection; D000069583:Pregabalin; D052616:Solid Phase Extraction / Q000379:methods; D000077236:Topiramate; D020888:Vigabatrin / Q000097:blood*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000077236:Topiramate; D005632:Fructose; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin
keywords: Fluorescence detection; Gabapentin; Pregabalin; Therapeutic drug monitoring; Topiramate; Vigabatrin