Pharmacokinetics and Metabolism Study of Deep-Sea-Derived Butyrolactone I in Rats by UHPLC-MS/MS and UHPLC-Q-TOF-MS

Mar Drugs. 2021 Dec 22;20(1):11. doi: 10.3390/md20010011.


Butyrolactone I (BTL-I) is a butanolide isolated from the deep-sea-derived fungus, Aspergillus sp. It provides a potential new target for the prevention and treatment of food allergies. This study aimed to investigate the metabolic and pharmacokinetic profile of BTL-I in rats. The metabolic profiles were obtained by UHPLC-Q-TOF-MS. As a result, eleven metabolites were structurally identified, and the proposed metabolic pathways of BTL-I were characterized. The main metabolites were the oxidative and glucuronidative metabolites. In addition, a sensitive UHPLC-MS/MS method was established for the quantitation of BTL-I in rat plasma (LOQ = 2 ng/mL). The method was fully validated and successfully applied to the pharmacokinetic study of BTL-I in rats after oral administration or intravenous administration. The oral bioavailability was calculated as 6.29%, and the maximum plasma concentrations were 9.85 ± 1.54 ng/mL and 17.97 ± 1.36 ng/mL for intravenous and intragastric dosing groups, respectively.

Keywords: butyrolactone I; food allergy; metabolism; pharmacokinetics.

MeSH terms

  • 4-Butyrolactone / administration & dosage
  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / blood
  • 4-Butyrolactone / pharmacokinetics
  • Administration, Oral
  • Animals
  • Anti-Allergic Agents / administration & dosage
  • Anti-Allergic Agents / blood
  • Anti-Allergic Agents / pharmacokinetics*
  • Aspergillus*
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Food Hypersensitivity / prevention & control
  • Infusions, Intravenous
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry


  • Anti-Allergic Agents
  • butyrolactone I
  • 4-Butyrolactone