Protocol for Therapeutic Drug Monitoring Within the Clinical Range Using Mid-infrared Spectroscopy

Therapeutic drug monitoring (TDM), which involves measuring drug levels in patients' body fluids, is an important procedure in clinical practice. However, the analysis technique currently used, i.e. liquid chromatography-tandem mass spectrometry (LC-MS/MS), is laboratory-based, so does not offer the short response time that is often required by clinicians. We suggest that techniques based on Fourier transform infrared spectroscopy (FTIR) offer a promising alternative for TDM. FTIR is rapid, highly specific and can be miniaturized for near-patient applications. The challenge, however, is that FTIR for TDM is limited by the strong mid-IR absorption of endogenous serum constituents. Here, we address this issue and introduce a versatile approach for removing the background of serum lipids, proteins and small water-soluble substances. Using phenytoin, an antiepileptic drug, as an example, we show that our approach enables FTIR to precisely quantify drug molecules in human serum at clinically relevant levels (10 μg/mL), providing an efficient analysis method for TDM. Beyond mid-IR spectroscopy, our study is applicable to other drug sensing techniques that suffer from the large background of serum samples.