Comparative metabolites profiles of osthole in normal and osteoporosis rats using liquid chromatography quadrupole time-of-flight mass spectrometry

J Pharm Biomed Anal. 2018 May 30:154:460-467. doi: 10.1016/j.jpba.2018.03.036. Epub 2018 Mar 20.

Abstract

Osthole is a derivative of coumnarin, which has been used to treat several diseases, including osteoporosis. To investigate the metabolite profile of osthole in osteoporosis rats was utilized to understand its underlying mechanisms of its anti-osteoporosis effect. In this study, plasma samples were collected from normal and osteoporosis rats after oral administration of osthole and analyzed to identify the metabolites of osthole by high performance liquid chromatography quadrupole time-of-flight mass spectrometry. By comparing the molecular weight and MS fragmentation of the metabolites with those of parent drug and reference standards, a total of 36 metabolites in plasma were identified. Demethylation, hydroxylation, hydroxymethylene loss and reduction, and subsequent glucuronidation, methylation and sulfation were the major metabolic pathways of osthole in both normal and osteoporosis rats. A specific hydration metabolic pathway was found in osteoporosis rats. These results provided a meaningful basis for studying the underlying mechanism of the anti-osteoporosis effect of osthole.

Keywords: Liquid chromatography quadrupole time-of-flight mass spectrometry; Metabolite; Osteoporosis; Osthole.

MeSH terms

  • Administration, Oral
  • Animals
  • Coumarins / blood*
  • Female
  • Mass Spectrometry
  • Metabolic Networks and Pathways / physiology*
  • Osteoporosis / blood*
  • Plasma / chemistry
  • Rats
  • Rats, Wistar

Substances

  • Coumarins
  • osthol