Determination and quantification of arbutin in plants using stable isotope dilution liquid chromatography–mass spectrometry

Arbutin is a very safe whitening agent for human skin. Since it is more expensive than other agents and has a challenging synthesis, novel methods to obtain this valuable agent are needed. In this study, we developed a precise and accurate method to detect and quantify arbutin using stable isotope dilution liquid chromatography–mass spectrometry (LC–MS). One challenge that needed to be overcome was the matrix effect occurring during the LC–MS analysis due to the analyte ionisation enhancement or suppression in the electrospray ionisation source by co-eluting compounds. Notably, arbutin had different matrix effects in the various sample matrices. A solution to this problem was the use of [ d 4 ]-arbutin as a stable isotope-labelled internal standard (SIL-IS), as it compensated the matrix effect of arbutin because it was affected by almost the same matrix effect. The validation of the developed method showed excellent linearity ( r 2 = 1.000), precision (relative standard deviation ≤ 2.5%), accuracy (recovery, 97.42–98.52%), limit of detection (0.03 μg/mL), and limit of quantification (0.1 μg/mL). Finally, the method of arbutin detection was applied to blueberry leaves to compare the precision and accuracy results obtained by performing stable isotope dilution using LC–MS and gas chromatography–mass spectrometry. The method was applied to strawberry leaves and pear peels, indicating that the SIL-IS method can be expected to find application in the arbutin analysis in other plants.