title: Derivatization of chiral carboxylic acids with (S)-anabasine for increasing detectability and enantiomeric separation in LC/ESI-MS/MS.
abstract: A simple and practical derivatization procedure for increasing the detectability and enantiomeric separation of chiral carboxylic acids in LC/ESI-MS/MS has been developed. (S)-Anabasine (ANA) was used as the derivatization reagent and rapidly reacted with carboxylic acids [3-hydroxypalmitic acid (3-OH-PA), 2-(β-carboxyethyl)-6-hydroxy-2,7,8-trimethylchroman (γ-CEHC), and etodolac] in the presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholium chloride. The resulting ANA-derivatives were highly responsive in ESI-MS operating in the positive-ion mode and gave characteristic product ions during MS/MS, which enabled sensitive detection using selected reaction monitoring; the detection responses of the ANA-derivatives were increased by 20-160-fold over those of the intact carboxylic acids and the limits of detection were in the low femtomole range (1.8-11 fmol on the column). The ANA-derivatization was also effective for the enatiomeric separation of the chiral carboxylic acids; the resolution was 1.92, 1.75, and 2.03 for 3-OH-PA, γ-CHEC, and etodolac, respectively. The derivatization procedure was successfully applied to a biological sample analysis; the derivatization followed by LC/ESI-MS/MS enabled the separation and detection of trace amounts of 3-OH-PA in neonatal dried blood spot and γ-CEHC in human saliva with a simple pretreatment and small sample volume.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan. higashi@rs.tus.ac.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Higashi
authors.forename: Megumi
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tadokoro
authors.forename: Shoujiro
authors.initials: S
authors.lastname: Ogawa
authors.forename: Haruhito
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukushima
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Toyo'oka
mesh_terms: D000328:Adult; D000691:Anabasine / Q000737:chemistry*; D002264:Carboxylic Acids / Q000097:blood / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D059788:Dried Blood Spot Testing / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012463:Saliva / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002264:Carboxylic Acids; D000691:Anabasine