title: Chiral analysis of ammuxetine enantiomers in dog plasma using online SPE/liquid chromatography with tandem mass spectrometric detection after precolumn chiral derivatization.
abstract: Ammuxetine (AMT), a novel chiral antidepressant candidate compound, exhibits better antidepression effects than duloxetine in different animal models. In this article, a chiral derivatization method, combined with online solid phase extraction (online SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), was developed for the chiral separation of AMT enantiomers after administration of racemic AMT to dogs. The derivatization reaction employed 2,3,4,6-tetra-O-acetyl-b-glucopyr-anosyl isothiocyanate (GITC) as a precolumn chiral derivatization reagent. A SPE column Retain PEP Javelin (10 × 2.1 mm) was used to remove proteins and other impurities in plasma samples. The enantiomeric derivatives were separated on a ZORBAX SB-C18column (50 × 2.1 mm × 3.5 μm) with an isocratic elution procedure. The selected multiple reaction monitoring mode of the positive ion was performed and the parent to the product transitions m/z 681.0/543.1 and m/z 687.4/543.1 were used to measure the derivatives of AMT and duloxetine (internal standard) with electrospray ionization. The method was validated in terms of specificity, linearity, sensitivity, precision, accuracy, matrix effect, and stability. The method was applied to a pharmacokinetics study of AMT racemate in dogs. The results suggested that the pharmacokinetic of AMT enantiomers might be stereoselective in dogs.
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Jimei
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Jiezhao
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Youzhi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Zheng
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Mei
authors.affiliation: Department of Pharmacy, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Ying
authors.identifier: 0000-0002-0325-7886
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D057230:Limit of Detection; D008297:Male; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods*; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry; D013876:Thiophenes / Q000097:blood* / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D013876:Thiophenes; C000627015:ammuxetine
keywords: GITC derivatization; SPE LC-MS/MS; ammuxetine enantiomers; dogs; pharmacokinetics; stereoselective analysis