In this study, a simple, quick, sensitive and reliable method utilizing ultrahigh performance liquid chromatography with tandem mass spectrometry method was validated for simultaneous quantification of six main 2-(2phenylethyl) chromones, including agarotetrol, isoagarotetrol, (5S,6R,7R,8S)-5,6,7,8-tetrahydroxy-(4-methoxyphenethyl)-5,6,7,8-tetrahydro-4H-chromen-4one, 8-chloro-2-(2-phenyl ethyl)-5,6,7-trihydroxy-5,6,7,8-tetrahydrochromone, 6,7-dimethoxy-2-(2-phenylethyl) chromone, and 2-(2-phenylethyl) chromone in rat plasma after oral administration of agarwood ethanol extract. Separation was performed on a Waters ACQUITY UPLC BEH C 18 column (2.1 × 100 mm, 1.7 μm) using gradient elution with mobile phase of 0.2% formic acid-water and acetonitrile. The tandem mass was performed in the multiple reaction monitoring mode with positive ionization. The calibration curves indicated good linearity (r 2 > 0.99) over the corresponding concentration range. The precision and accuracy were within the acceptable range. Mean absolute recoveries of all analytes were between 73.31% and 94.76%, and the relative standard deviations of matrix effects were not higher than 15%. The six analytes were proven to be stable during sample storage and analysis procedures. The validated method was successfully applied to pharmacokinetic study of six 2-(2-phenylethyl) chromones in rat after oral administration of agarwood ethanol extract for the first time. This study could serve as a reference and provide theoretical guidance for further pharmacodynamic research and clinical applications of agarwood.
K E Y W O R D S2-(2-phenylethyl) chromones, agarwood, pharmacokinetic study, rat plasma, traditional Chinese medicine Article Related Abbreviations: AUC 0-t , the area under curve; C max , the maximum plasma concentration; IS, internal standard; LLOQ, lower limit of quantification; MRM, multiple reaction monitoring; MRT, mean residence time; RE, relative error; T max , the time to peak concentration