446 KB36 KB199820252015Grabnar, IztokMilosheska, DanielaRoškar, RobertVovk, Tomažštevilka:2letnik:62str. 411-419ISSN:1318-0207COBISSID:3880305URN:URN:NBN:SI:doc-FCQNZ25ZenSlovensko kemijsko društvoActa chimica slovenicačloveška plazmatekočinska kromatografija visoke ločljivosti s fluorescenčno detekcijoterapevtsko nadziranje zdravilatopiramatSimple and sensitive high performance liquid chromatography method with fluorescence detection for therapeutic drug monitoring of topiramate|Objective of the present report was to develop and validate a simple, sensitive, reliable, inexpensive and reproducible HPLC method with fluorescence detection (HPLC-FLD), suitable for routine therapeutic drug monitoring (TDM) of an antiepileptic drug topiramate. The determination of plasma topiramate concentration was carried out after precolumn derivatization, using 4-chloro-7-nitrobenzofurazan as a fluorescent labeling agent and bendroflumethiazide as an internal standard. The standard calibration curve was linear over the concentration range of 0.01-24 microg/mL (r2> 0.9998). The intra- and inter-day accuracies expressed as bias were from 1.41 to 9.95 % and from 1.85 to 10.23 %, respectively. The intra- and inter-day precisions were below 7.87 % and 2.73 %, respectively. A simple, sensitive, accurate, precise and inexpensive HPLC-FLD method for determination of topiramate in human plasma was developed and validated. The validated method was applied for the measurement of plasma topiramate concentrations in patients with epilepsy. The reported method is appropriate for TDM of topiramate as well as for pharmacokinetic and bioequivalence studiesRazvili in validirali smo analizno metodo, ki temelji na tekočinski kromatografiji visoke ločljivosti s fluorescenčno detekcijo in omogoča rutinsko terapevtsko spremljanje plazemskih koncentracij protiepileptičnega zdravila topiramata pri bolnikih z epilepsijo. Koncentracijo topiramata v plazmi smo določali po predkolonski derivatizaciji, z uporabo 4-kloro- 7-nitrobenzofurazana kot fluorescenčnega reagenta za označevanje in bendroflumetiazida kot internega standarda. Metoda je enostavna, občutljiva, zanesljiva, ponovljiva, selektivna in ima območje linearnosti pri koncentracijah od 0,01 do 24 microg/mL (r2 > 0.9998). Znotraj dnevna točnost, izražena kot odstopanje od prave vrednosti, je od 1,4 do 9,9 %, meddnevna pa od 1,9 do 10,2 %. Znotraj dnevna in meddnevna natačnost metode, izraženi kot relativni standardni odklon, pa sta boljši od 7,9 oziroma 2,7 %. Validirano metodo smo uporabili za merjenje plazemskih koncentracij topiramata pri bolnikih z epilepsijo, s čimer smo potrdili njeno primernost za terapevtsko spremljanje topiramata. Poleg tega je metoda uporabna tudi za določanje topiramata v farmakokinetičnih in bioekvivalečnih študijahTEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaSlovensko kemijsko društvo