Several chemical and biological studies have revealed R,S-goitrin as the main bioactive constituent of Isatis indigotica Fort., responsible for antiviral antiendotoxin activity; however, few pharmacokinetic studies have been conducted. To comprehend the kinetics of R,S-goitrin and promote its curative application, a rapid and sensitive UHPLC-MS/MS method was developed. The selected reaction monitoring transitions were m/z 130.0 → 70.0 for R,S-goitrin and m/z 181.1 → 124.0 for the internal standard in a positive-ion mode. The established UHPLC-MS/MS method achieved good linearity for R,S-goitrin at 10-2000 ng/mL. The intra- and interday accuracy levels were within ±9.7%, whereas the intraday and interday precision levels were <11.3%. The extraction recovery, stability and matrix effect were within acceptable limits. The validated method was successfully applied for the pharmacokinetic analysis of R,S-goitrin in rats after oral administration. Moreover, a total of six metabolites were structurally identified through UHPLC-Q/TOF-MS. The proposed metabolic pathways of R,S-goitrin in rats involve demethylation, acetylation, glutathionylation and oxygenation.
Keywords: LC-MS/MS; LC-Q/TOF-MS; R,S-goitrin; drug metabolism; pharmacokinetics.
© 2019 John Wiley & Sons, Ltd.