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Chiral analysis of ammuxetine enantiomers in dog plasma using online SPE/liquid chromatography with tandem mass spectrometric detection after precolumn chiral derivatization
Author(s) -
Yu Jimei,
Li Xin,
Zhou Jiezhao,
Xie Xiangyang,
Chen Meiling,
He Xinhua,
Yang Yang,
Zhang Youzhi,
Zheng Aiping,
Mei Xingguo,
Li Ying
Publication year - 2017
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22692
Subject(s) - chemistry , chromatography , derivatization , enantiomer , selected reaction monitoring , tandem mass spectrometry , electrospray ionization , solid phase extraction , liquid chromatography–mass spectrometry , elution , electrospray , chiral derivatizing agent , mass spectrometry , chiral column chromatography , high performance liquid chromatography , organic chemistry
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‐C 18 column (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.