title: Fluorous derivatization and fluorous-phase separation for fluorometric determination of naproxen and felbinac in human plasma.
abstract: Fluorous derivatization followed by fluorous-phase liquid chromatographic (LC) separation exploits the affinity between perfluoroalkyl compounds for highly selective and quantitative isolation of various analytes. However, the applicability of this technique as a simple pretreatment for fluorometric determination in clinical settings has not been fully explored. Here we show the applicability of this technique to the clinical determination of non-steroidal anti-inflammatory drugs (NSAIDs) in human plasma. Naproxen and felbinac, widely used native-fluorescent NSAIDs with a carboxyl group, can have toxic effects at acute doses, and were therefore chosen as representative NSAIDs. Samples were precolumn derivatized with a non-fluorescent fluorous amine, which allowed highly selective retention of only derivatized substances in the fluorous LC column. Thus, subsequently, only the retained fluorous-labeled and fluorescent analytes were detected fluorometrically at appropriate retention times. The detection limits for these two drugs were less than 11fmol on column. Correlation curves were liner over the range of 0.04-10 and 5-250nmol/mL plasma for both two drugs (r>0.999) with good repeatability. Thus, this method offers a simple, sensitive, and selective solution for determination of NSAIDs in clinical settings.
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, Johnan, Fukuoka 814-0180, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hayama
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshitake
authors.forename: Miki
authors.initials: M
authors.lastname: Itoyama
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Todoroki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nohta
mesh_terms: D000328:Adult; D053000:Analytic Sample Preparation Methods; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005466:Fluorocarbons / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry; D057230:Limit of Detection; D008297:Male; D008832:Microchemistry / Q000379:methods*; D009025:Morpholines / Q000737:chemistry; D009288:Naproxen / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D010648:Phenylacetates / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence; D013678:Technology, Pharmaceutical; D055815:Young Adult
chemical_list: C558756:4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoro-n-undecylamine; C467606:4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005466:Fluorocarbons; D007202:Indicators and Reagents; D009025:Morpholines; D010648:Phenylacetates; C012776:biphenylylacetic acid; D009288:Naproxen