2. Academic Validation
  3. The in vitro/in vivo metabolic pathways analysis of lobetyol, lobetyolin, and lobetyolinin, three polyacetylenes from Codonopsis Radix, by UHPLC-Q/TOF-MS and UHPLC-MS/MS

The in vitro/in vivo metabolic pathways analysis of lobetyol, lobetyolin, and lobetyolinin, three polyacetylenes from Codonopsis Radix, by UHPLC-Q/TOF-MS and UHPLC-MS/MS

  • J Pharm Biomed Anal. 2023 Jan 20;223:115140. doi: 10.1016/j.jpba.2022.115140.
Qi Xie 1,  Hanxue Wang 1,  Huida Guan 1,  Nan Xu 1,  Xiang Zhao 1,  Xuemei Cheng 1,  Changhong Wang 2
Affiliations

Affiliations

  • 1 Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Road, Shanghai 201203, China.
  • 2 Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai R&D Centre for Standardization of Chinese Medicines, 1200 Cailun Road, Shanghai 201203, China. Electronic address: [email protected].
PMID: 36356406 DOI: 10.1016/j.jpba.2022.115140
Abstract

Polyacetylenes, lobetyol, lobetyolin and lobetyolinin, are responsible for antitumor, antioxidant, anti-inflammatory, immunomodulatory activities of Codonopsis Radix. However, their metabolic pathways are still unknown. The study was purposed to investigate the metabolism of three polyacetylenes in vitro and in vivo by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Moreover, a rapid, sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative and semi-quantitative determination of lobetyol and its 12 metabolites to investigate the metabolic stability and metabolic phenotypes. A total of 47, 30 and 34 metabolites of lobetyol, lobetyolin and lobetyolinin were found in all samples. These metabolites are produced through extensive pathways, mainly involving oxidation, glucuronidation and glutathione conjugation. Lobetyol showed good metabolic stability in liver microsomes. The results of both recombinant human CYP enzymes and chemical inhibition experiments confirmed that CYP2C19, 1A1, 2C9, and 1A2 are the major isozymes mediating lobetyol metabolism.

Keywords

Codonopsis Radix; Lobetyol; Lobetyolin; Lobetyolinin; Metabolism; Polyacetylenes.

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