Protocol for\nTherapeutic Drug Monitoring Within the\nClinical Range Using Mid-infrared Spectroscopy

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