title: (S)-1-(4-Dimethylaminophenylcarbonyl)-3-aminopyrrolidine: a derivatization reagent for enantiomeric separation and sensitive detection of chiral carboxylic acids by LC/ESI-MS/MS.
abstract: A novel derivatization reagent, (S)-1-(4-dimethylaminophenylcarbonyl)-3-aminopyrrolidine (1-DAPAP), was developed for increasing the detection sensitivity and enantiomeric separation of chiral carboxylic acids by liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS). 1-DAPAP reacted with carboxylic acids at room temperature within 5min in the presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The epimerization (racemization) during the derivatization reaction was negligible. The resulting derivatives were highly responsive during the ESI-MS operating in the positive-ion mode and gave a characteristic product ion during the MS/MS, which enabled the sensitive detection using selected reaction monitoring; the detection responses of the 1-DAPAP-derivatives were increased by 10-1100-fold over the intact carboxylic acids and the limits of detection ranged from 0.97 and 5.2fmol on the column. The 1-DAPAP-derivatization was also effective for the enantiomeric separation of chiral carboxylic acids; the resolution values were 1.2-4.3 for the evaluated carboxylic acids. The derivatization procedure was successfully applied to biological sample analyses; the derivatization followed by LC/ESI-MS/MS enabled the separation and detection of trace amounts of ibuprofen and naproxen in human saliva with a simple pretreatment and small sample volume.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278 8510, Japan.
authors.forename: Shoujiro
authors.initials: S
authors.lastname: Ogawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tadokoro
authors.forename: Maho
authors.initials: M
authors.lastname: Sato
authors.forename: Takehisa
authors.initials: T
authors.lastname: Hanawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Higashi
mesh_terms: D029681:Arabidopsis Proteins / Q000737:chemistry; D002264:Carboxylic Acids / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057230:Limit of Detection; D009025:Morpholines / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: C467606:4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; D029681:Arabidopsis Proteins; D002264:Carboxylic Acids; C581866:LAMP1 protein, Arabidopsis; D009025:Morpholines; D011759:Pyrrolidines
keywords: Chiral carboxylic acid; Derivatization reagent; Enantiomeric separation; Increasing sensitivity; LC/ESI-MS/MS