Surface-enhanced Raman spectroscopy for therapeutic drug monitoring in oncology: a study on sample preparation

Reproducible quantification of drugs using surface-enhanced Raman spectroscopy (SERS) is currently drawing considerable attention in the research field of therapeutic drug monitoring (TDM) for cancer therapy, due to the possibility to provide analyses of drugs in body fluids within few minutes, with comparable or smaller errors with respect to routine TDM methods. However, clinical samples are complex mixtures containing lipids and proteins that can bind the drug of interest; thus only a fraction of the drug molecules will be free to interact to the metal surface, and, hence, to benefit from the signal enhancement. Sample preparation methods and experimental conditions must be carefully evaluated to obtain interpretable and comparable results. Here we report the development of a standardized preanalytical method for two chemotherapeutic drugs, imatinib and irinotecan, both exhibiting strong affinity to plasma proteins. To find the most efficient method for sample preparation, we analyzed different protein precipitation methods as well as ultrafiltration, for both reproducibility and reduction of matrix effect.