title: Utility of postcolumn addition of 2-(2-methoxyethoxy)ethanol, a signal-enhancing modifier, for metabolite screening with liquid chromatography and negative ion electrospray ionization mass spectrometry.
abstract: A strategy for highly sensitive metabolite screening by liquid chromatography-electrospray ionization (ESI) mass spectrometry with the negative-ion mode that involves the use of a reversed-phase column in gradient-elution mode and postcolumn addition of 2-(2-methoxyethoxy)ethanol (2-MEE), a novel signal-enhancing modifier, has been described. When a mobile phase of 50 mM ammonium acetate/acetic acid buffer (pH 4.4) at a flow rate of 100 microL/min was employed, poor ESI response of ibuprofen as a model drug, probably due to both the high surface tension of the mobile phase and the ion-suppression effect of acetate anion in the mobile phase, was observed. On the other hand, the postcolumn addition of 2-MEE (50 microL/min) into the mobile phase counteracted the ion suppression as well as the surface tension problem, resulting in approximately 100-fold signal enhancement of the analyte. The metabolite screening of ibuprofen in human urine was subsequently carried out comparing the results with and without postcolumn addition of 2-MEE. The results indicated that the postcolumn addition of 2-MEE dramatically improved the ESI responses of all urinary metabolites detected without affecting the chromatographic separation.
authors.affiliation: Drug Metabolism Laboratory, Taisho Pharmaceutical Co., Ltd., Saitama, Japan. s13557@ccm.taisho.co.jp
authors.forename: J
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: M
authors.initials: M
authors.lastname: Ohmichi
authors.forename: S
authors.initials: S
authors.lastname: Jingu
authors.forename: N
authors.initials: N
authors.lastname: Ogawa
authors.forename: S
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000652:urine; D002853:Chromatography, Liquid / Q000379:methods*; D000431:Ethanol / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D007052:Ibuprofen / Q000652:urine; D007202:Indicators and Reagents / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*
chemical_list: C403469:2-(2-methoxyethoxy)ethanol; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D000431:Ethanol; D007052:Ibuprofen