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Simultaneous multiphase detection of multiplex analytes is important, albeit challenging, especially in pharmaceuticals analysis since drugs with lipid and water solubility were often administrated together for synergistic therapy. Surface-enhanced Raman spectroscopy (SERS) is a label-free and sensitive tool for multiplex analytes detection at multiphase interfaces. However, the requirements of inducers or surfactant surface modification of the SERS substrate have restricted extensive applications. Herein, we developed a graphene-isolated-Au-nanocrystal based multiphase analysis system. Unexpectedly, the gold graphitic SERS substrate can simply suspend at the interface of the different phase without the involvement of any surfactant. Therefore, the proximity of substrate with analyte molecules remains unaffected. Such suspended substrate not only ensures sensitive SERS detection but also enables the enrichment of analytes from the different phase simultaneously without interference. Moreover, the graphitic shell of the SERS substrate has a unique vibration band located in the Raman biological silence region which is utilized as the internal standard and improves the SERS quantification accuracy. Efficient ex vivo multiphase enrichment and detection of mimic lipid- and water-soluble drugs injected into mice were demonstrated with such gold graphitic substrate, showing the potential of this simultaneous multiplex pharmacokinetic analysis.

Surfactant-Free Interface Suspended Gold Graphitic Surface-Enhanced Raman Spectroscopy Substrate for Simultaneous Multiphase Analysis