title: Simple and practical derivatization procedure for enhanced detection of carboxylic acids in liquid chromatography-electrospray ionization-tandem mass spectrometry.
abstract: A simple and practical derivatization procedure for increasing the detection responses of carboxylic acids in liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) has been developed. 2-Hydrazinopyridine (HP) and 2-picolylamine (PA) rapidly reacted with biologically and clinically important carboxylic acids [chenodeoxycholic acid, glycochenodeoxycholic acid, prostaglandin E2, 2-(-carboxyethyl)-6-hydroxy-2,7,8-trimethylchroman (gamma-CEHC),alpha-lipoic acid, homovanillic acid (HVA) and 5-hydroxyindole-3-acetic acid] in the presence of 2,2'-dipyridyl disulfide and triphenylphosphine. The resulting HP- and PA-derivatives were highly responsive in ESI-MS operating in the positive-ion mode and gave characteristic product ions during MS/MS, which enabled the sensitive detection using selected reaction monitoring. Among the two reagents, PA was of more practical use; the detection responses of the PA-derivatives were increased by 9-158-fold over the intact carboxylic acids and the limits of detection were in the low femtomole range (1.5-5.6 fmol on column). The PA-derivatization was successfully applied to a biological sample analysis; the derivatization followed by LC-ESI-MS/MS enabled the detection of trace amounts of bile acids, gamma-CEHC and HVA in human saliva with a simple pretreatment, small sample volume and short analysis time.
authors.affiliation: School of Pharmaceutical Sciences and Global COE Program, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. higashi@u-shizuoka-ken.ac.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Higashi
authors.forename: Takuya
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Inagaki
authors.forename: Jun Zhe
authors.initials: JZ
authors.lastname: Min
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukushima
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Toyo'oka
mesh_terms: D002264:Carboxylic Acids / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D012463:Saliva / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002264:Carboxylic Acids