title: Determination of topiramate in human plasma using liquid chromatography tandem mass spectrometry.
abstract: The LC-MS/MS method for determination of the anti-epileptic drug topiramate (TPM) in human plasma was developed and validated for pharmacokinetic and bioequivalence study purposes. For quantitative determination of TPM values the method with deuterated internal standard (topiramate-d12) and liquid chromatography with tandem mass spectrometry was used. TPM was extracted from the human plasma using the solid-phase extraction procedure on a Strata X extraction column. Negative ions were monitored in the selected reaction monitoring mode (SRM) and transitions m/z 338.2 > 78.2 and m/z 350.3 > 78.2 were used for the quantitative evaluation of TPM and the internal standard, respectively. The results obtained from validation were statistically evaluated according to the requirements of European Medicines Agency (EMA) and Food and Drug Administration (FDA) regulatory guidelines. The linearity of the method was checked within a concentration range from 10 to 2000 ng/mL. Successful validation confirmed that this method is precise, accurate, sensitive and therefore suitable for determination of topiramate plasma levels in pharmacokinetic and bioequivalence studies.
authors.affiliation: Krka, d.d., Novo mesto, Smarjeska cesta 6, SI-8501 Novo mesto, Slovenia. tanja.vnucec-popov@krka.biz
authors.forename: Tanja Vnucec
authors.initials: TV
authors.lastname: Popov
authors.forename: Lea Cvitkovic
authors.initials: LC
authors.lastname: Maricic
authors.forename: Helena
authors.initials: H
authors.lastname: Prosen
authors.forename: Darinka Brodnjak
authors.initials: DB
authors.lastname: Voncina
mesh_terms: D002851:Chromatography, High Pressure Liquid; D005632:Fructose / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D053719:Tandem Mass Spectrometry; D000077236:Topiramate
chemical_list: D000077236:Topiramate; D005632:Fructose