Citation: HUAI Bin-Bin, GUO Chun-Na, LI Qiang, GAO Jin, XIE Shun, HUANG Xian-Hui. In vivo Identification of Metabolites of Pyrimethamine in Rats by Liquid Chromatography-Linear Ion Trapped-Orbitrap Mass Spectrometry[J]. Chinese Journal of Analytical Chemistry, ;2016, 44(1): 32-40. doi: 10.11895/j.issn.0253-3820.150309 shu

In vivo Identification of Metabolites of Pyrimethamine in Rats by Liquid Chromatography-Linear Ion Trapped-Orbitrap Mass Spectrometry

1.
College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues, South China Agricultural University, Guangzhou 510640, China

Corresponding author: HUANG Xian-Hui,
Received Date: 17 April 2015
Available Online: 12 September 2015
Fund Project: 本文系农业行业标准制修订项目(No.201391194)资助 (No.201391194)

The metabolism of pyrimethamine (PYR) after a single oral administration at a dose of 5 mg/kg in rats was investigated. In vivo samples including rat plasma, urine and feces were collected respectively at different times. We performed liquid chromatography tandem two-dimensional linear ion trapped orbitrap mass spectrometry spectrometer (LC-LTQ-Orbitrap MS) to identify the unknown metabolites of PYR. Then 10 metabolites of PYR were found in rats with this approach, which indicates that hydroxylation on benzene ring, N-oxidation, dioxidation, N-glucuronidation, methylation+glucuronidation, hydroxylation+glucuronidation and N-oxidation+glucuronidation were the major metabolic pathways of PYR in rats. 9 of these metabolites were identified in vivo for the first time while the PYR 3-N-oxide was ever detected in vitro metabolism of PYR in isolated rat liver. We identified the structure of the metabolites according to their accurate mass data and the characteristic MSn product ions. Based on the above analyses, we proposed the phase I and II metabolic pathways for PYR in rat. The major phase I metabolites were formed via hydroxylation and N-oxidation pathways, and the major phase II metabolites were methylation and glucuronidation.
- Pyrimethamine,
- Rats,
- Liquid chromatography tandem two-dimensional linear ion trapped-orbitrap mass spectrometry,
- Metabolites
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沈阳化工大学材料科学与工程学院沈阳 110142