Menthol is a monocyclic monoterpene with a distinct flavor that is frequently utilized in a variety of food and medicinal items. In this study, a sensitive method based on quartz crystal microbalance (QCM) with gold nanoparticles amplification was developed. A gold chip was initially modified with mono(6-mercapto-6-deoxy)-β-cyclodextrin (SH-β-CD) through Au-S affinity binding. When menthol is absent, the host–guest interaction brings ferrocene (Fc) labeled-ssDNA (Fc-ssDNA) to enter the SH-β-CD cavity. The hybridization between Au nanoparticles functionalized-ssDNA (AuNPs-ssDNA) and Fc-ssDNA produces a significant frequency shift. However, in the presence of menthol, the inclusion competition between Fc and menthol reduces AuNPs-ssDNA modification on the chip surface. In this case, the change of QCM frequency is greatly reduced by menthol. Thus, menthol determination is accomplished by measuring the change in QCM frequency with a linear range from 10−8 M to 10−2 M and a limit of detection of 7.81 nM, which is superior to previously reported results. The method has also been applied in real samples such as mint and essential oil with satisfactory results.
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