Ultrasensitive SERS substrate for label-free therapeutic drug monitoring of chlorpromazine hydrochloride and aminophylline in human serum.

Surface-enhanced Raman spectroscopy (SERS) has been widely used in the field of therapeutic drug monitoring (TDM) because of its powerful fingerprinting capability. In this paper, we used an in situ synthesis method to anchor Ag nanoparticles (AgNPs) on the surface of MIL-101(Cr) to obtain MIL-101(Cr)@Ag. Owing to the large specific surface area and ultra-high porosity of MIL-101(Cr)@Ag, we developed a method for the determination of chlorpromazine hydrochloride (CPZ) and aminophylline (AMP) in human serum by using it as a solid-phase extraction sorbent and SERS substrate. The label-free TDM-SERS method was able to evaluate the levels of CPZ and AMP in serum samples with detection limits as low as 8.91 × 10-2 µg/mL and 3.4 × 10-2 µg/mL, respectively. In addition, influencing factors including sample solution pH, AgNO3 concentration, drug adsorption time, and the amount of sample solution were optimized. This protocol provides a new method with good selectivity, stability, reproducibility, homogeneity, and sensitivity for the determination of small-molecule drug content in serum samples. This label-free TDM-SERS method will help to achieve rapid individualized dosing regimens in clinical practice and has potential applications in the field of TDM.