Comprehensively investigating pharmacokinetics and metabolic fate of andrographolide in rats by liquid chromatography/mass spectrometry-based approach

Abstract

Andrographolide, a natural labdane diterpenoid lactone isolated from Andrographis paniculata, possesses diverse pharmacological properties such as anti-tumor, anti-inflammatory, antiviral, and immunomodulatory activities, rendering it a promising candidate for therapeutic development. In this study, pharmacokinetic profiles, excretion features, and metabolism of andrographolide were systematically investigated in rats using a liquid chromatography/mass spectrometry (LC/MS)-based approach. Following intravenous and oral administration, andrographolide exhibited high elimination and moderate bioavailability. Excretion study revealed that less than 5% of the administered dose was eliminated in its parent form in urine and feces. Metabolic profiling identified a total of 39 analytes, among which 34 were sulfated conjugates—establishing sulfation as the most structurally diverse metabolic pathway of andrographolide in rats. A novel MS/MS fragmentation workflow was established, which enabled the unambiguous discrimination of four sulfation modification sites: O-sulfation at the C3 and C19 positions, and C-sulfation at the C12 and C14 positions. Collectively, this comprehensive study delineates the complete in vivo disposition of andrographolide in rats and clarifies the site-specific sulfation rules of its metabolites.