Method development and validation for pharmacokinetic and tissue distributions of ellagic acid using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Linlin Yan,Chao Ma,Peipei Yin,Yujun Liu

doi:10.3390/molecules191118923

Linlin Yan, Chao Ma + Show 2 more

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https://doi.org/10.3390/molecules191118923

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Journal: Molecules (Basel, Switzerland)	Publication Date: Nov 18, 2014
Citations: 56	License type: CC BY 4.0

Affiliation: Beijing Forestry University

Abstract

Ellagic acid is a dietary polyphenol found in numerous fruits and vegetables, possessing several health benefits such as antioxidant, anticancer and anti-atherosclerotic biological properties. The purpose of this study was to explore the pharmacokinetics and tissue distribution of ellagic acid in rats. A simple, rapid, sensitive and specific liquid chromatography–tandem mass spectrometry method to determine the ellagic acid in plasma and tissue samples was developed and validated. The separation was achieved using reversed-phase ultra-performance liquid chromatography (UPLC), and the mass spectrometric detection was achieved using heated electrospray ionization (negative mode) and multiple ion monitoring (m/z 301/229). A sample cleanup with a solid phase extraction (SPE) step prior to the UPLC-MS/MS analysis was also developed. The SPE and UPLC-MS/MS method established here was successfully applied to reveal the pharmacokinetic profiles and tissue distribution of ellagic acid. After oral administration dosing at 50 mg/kg, plasma levels of ellagic acid peaked at about 0.5 h, with Cmax value of 93.6 ng/mL, and the results showed that the ellagic acid was poorly absorbed after oral administration. The pharmacokinetic profile of ellagic acid fitted to a two-compartment model with t1/2α 0.25 h and t1/2β 6.86 h, respectively. Following oral administration, ellagic acid was detected in all examined tissues including kidney, liver, heart, lung and brain et al., and the highest levels were found in kidney and liver.

Highlights

Ellagic acid (EA) and hydrolysable ellagitannins (ETs) are dietary polyphenols found in numerous fruits, vegetables and nuts such as pomegranate, blackberry, raspberry, chestnut, and walnut [1,2]
The conventional organic solvent deproteinization and extraction method was used as follows: 400 μL of methanol or acetonitrile was added to 100 μL of blank plasma spiked with 1 μg of EA and vortex mixed for 5 min
high-performance liquid chromatography (HPLC)-DAD analysis revealed that the recoveries for methanol and acetonitrile treatment of EA in plasma were only 17.8% and 13.1%, respectively, conventional organic solvent deproteinization and extraction methods are not suitable for EA detection in plasma

Summary

Introduction

Ellagic acid (EA) and hydrolysable ellagitannins (ETs) are dietary polyphenols found in numerous fruits, vegetables and nuts such as pomegranate, blackberry, raspberry, chestnut, and walnut [1,2]. EA is known to possess many health benefits such as antioxidant, anticancer, antiatherosclerotic and other biological properties [1,2,3]. Elucidating the pharmacokinetic and tissue distribution profiles of EA is important, which can increase our understanding of the health beneficial mechanisms and provide more information for the scientific consumption of EA or EA/ETs-rich foods. The first study on the metabolism of EA was performed in rats after oral administration, and the concentrations of EA and its metabolites in urine and feces were reported [4]. The tissue distribution of EA in mice after oral administration was studied [5]

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