Pharmacokinetic analysis and tissue distribution of andrographolide in rat by a validated LC-MS/MS method

Abstract

Context: Andrographis paniculata (Burm.f.) Nees (Acanthaceae) is widely used in tribal medicine in India and some other countries for multiple clinical applications. It contains andrographolide (AG) (diterpenoid lactone), a major phytomarker which probably accounts for its medicinal properties. Objective: This study investigates the site-specific distribution of AG in different tissues of rats and its pharmacokinetic parameter evaluation by using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Materials and methods: A simple and sensitive LC-MS/MS method has been developed and validated to quantify the presence of AG in plasma and various tissues of rat following oral administration of A. paniculata extract and AG in a dose of 133.33 and 100mg/kg/day, respectively, for four weeks. Results: The present study showed that the highest concentration of AG was in kidney (156.12ng/g) followed by liver, spleen and brain while almost same concentration was found in heart and lung. The apparent Cmax, Tmax, elimination half-life and total exposure (AUC0-α) were 115.81ng/ml, 0.75, 2.45 and 278.44ngh/ml, respectively. Conclusion: This was an attempt to determine the presence of AG (a known biomarker) in tissues such as kidney, heart, lungs, brain and plasma of rats using a validated LC-MS/MS method. Furthermore, the observed reduced concentration in plasma and various tissues from 1 to 8h might be attributed to relatively rapid elimination or distribution of AG from the central compartment. © 2014 Informa Healthcare USA, Inc. All rights reserved.