A stable isotope dilution tandem mass spectrometry method of major kavalactones and its applications.

Yi Wang,Shainnel O Eans,Linda Haddad,Bonnie A Avery,Chengguo Xing,Sreekanth C Narayanapillai,Abhisheak Sharma,Naomi Fujioka,Heather M Stacy,Jay Mclaughlin,Carla A Ng

doi:10.1371/journal.pone.0197940

Abstract

Kava is regaining its popularity with detailed characterizations warranted. We developed an ultraperformance liquid chromatography high-resolution tandem mass spectrometry (UPLC-MS/MS) method for major kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin and desmethoxyyangonin) with excellent selectivity and specificity. The method has been validated for different matrices following the Food and Drug Administration guidance of analytical procedures and methods validation. The scope of this method has been demonstrated by quantifying these kavalactones in two kava products, characterizing their tissue distribution and pharmacokinetics in mice, and detecting their presence in human urines and plasmas upon kava intake. As expected, the abundances of these kavalactones differed significantly in kava products. All of them exhibited a large volume of distribution with extensive tissue affinity and adequate mean residence time (MRT) in mice. This method also successfully quantified these kavalactones in human body fluids upon kava consumption at the recommended human dose. This UPLC-MS/MS method therefore can be used to characterize kava products and its pharmacokinetics in animals and in humans.

Highlights

Kava is a beverage in the South Pacific regions
We have developed an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) coupled with the high-resolution Orbitrap, which minimizes the isobaric interferences from the matrix, resulting in increased sensitivity and specificity [36, 37]
The observed ions [M+H]+ of the pure kavalactones at the full MS scan stage had excellent agreement with the calculated m/z values. Their reconstructed ion chromatograms and product ion spectra were assayed by online UPLC-MS/MS (S1 Fig)

Summary

Introduction

Kava is a beverage in the South Pacific regions. It has been documented to help people relax, socialize and improve the quality of sleep [1]. The traditional form of kava is prepared by grinding the rhizome of kava (Piper methysticum Forst) in ambient temperature water or coconut milk. Kava can be prepared by extracting the rhizomes with ethanol or acetone. A number of clinical studies suggest that kava has an anxiolytic effect with the organic extract preparation once marketed as an anxiolytic agent [2,3,4].

Methods

Results

Conclusion