Vibrational study of mycophenolic acid and its quantification with electrochemically assisted surface-enhanced Raman spectroscopy.

Mycophenolic acid (MPA) is an immunosuppressant widely used in transplantations, for which therapeutic drug monitoring (TDM) has proven beneficial. There is furthermore a need to develop affordable, rapid, and benchtop analytical methods to perform TDM of MPA in a point-of-need setting. In this paper, we report for the first time the Raman fingerprint region and surface-enhanced Raman spectroscopy (SERS) vibrations of MPA through density functional theory calculations. The output of these simulations was compared with experimental data from electrochemically assisted SERS, i.e. application of a well-defined potential or sequence of potentials in SERS assays. The systematic electrochemically assisted SERS experimental study was carried out to understand the adsorption behaviour of MPA on gold nanopillars (AuNPs) when different potentials were applied. We found that MPA interacts with the AuNPs through its benzofuran heterocycle and carboxylic acid group. Applying different potentials on the SERS substrate resulted in band shifts, which we hypothesise to originate from molecular reorientation on the metal surface. Moreover, an electrochemically assisted SERS assay was developed and carried out on a portable Raman spectrometer. We show that MPA detection can be performed in less than 5 min in a clinically relevant concentration range (1 – 50 µM), with improved repeatability compared to a SERS assay without any applied potential (overall RSD decrease from 34.6 % to 18.5 %). [Display omitted] • First Raman and SERS vibrational study of mycophenolic acid (MPA) through DFT. • MPA molecular orientation on Au Nanopillars was studied. • An electrochemically assisted SERS assay was developed for MPA determination. • Quantification of MPA in a clinically relevant range (1–50 µM) in PBS. [ABSTRACT FROM AUTHOR]