title: Design and synthesis of a novel pre-column derivatization reagent with a 6-methoxy-4-quinolone moiety for fluorescence and tandem mass spectrometric detection and its application to chiral amino acid analysis.
abstract: A new pre-column derivatization reagent with a 6-methoxy-4-quinolone (6-MOQ) moiety for amino acid analysis, 2,5-dioxopyrrolidin-1-yl(2-(6-methoxy-4-oxoquinolin-1(4H)-yl)ethyl) carbonate (6-MOQ-EtOCOOSu), was designed and synthesized. 6-MOQ is a thermo/photostable fluorophore with a high proton-affinity site and sensitive determination could be carried out by a fluorescence detector and also by an electrospray ionization mass spectrometer. Derivatization of amino acids with 6-MOQ-EtOCOOSu was completed within 1 min under mild basic conditions at room temperature. The 6-MOQ derivatives of all chiral proteinogenic amino acids were separated using the combination of three enantioselective columns, Chiralpak QN-AX, Chiralpak ZXIX(+), and KSAACSP-001S, with separation factors of higher than 1.07. The present reagent enables the sensitive determination of amino acid enantiomers, and the values of LLOD using a chiral-HPLC-MS/MS system were 0.05-50 fmol/injection.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Shiseido Irica Technology Inc., 12 Nishikawabecho, Higashikujo, Minami-ku, Kyoto 601-8037, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Negishi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Onigahara
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Kusano
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Miyoshi
authors.affiliation: Shiseido Co., Ltd., 1-6-2, Higashi-shimbashi, Minato-ku, Tokyo 105-8310, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mita
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakazono
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Ohtsuki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Ojida
authors.affiliation: Institute of Analytical Chemistry, University of Vienna, Waehringerstrasse 38, A-1090 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lindner
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: hamase@phar.kyushu-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hamase
mesh_terms: D000596:Amino Acids / Q000032:analysis* / Q000737:chemistry; D000818:Animals; D015195:Drug Design; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015363:Quinolones / Q000737:chemistry*; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C500010:6-methoxy-4-quinolone; D000596:Amino Acids; D005456:Fluorescent Dyes; D015363:Quinolones
keywords: Amino acid; Chiral separation; Derivatization reagent; Fluorescence; MS/MS