title: Toward SERS-based point-of-care approaches for therapeutic drug monitoring: the case of methotrexate.
abstract: To date, in spite of their toxicity, the plasmatic concentration of most chemotherapeutic drugs is difficult to monitor in oncological patients, because their quantitative determination is expensive and time consuming. This contribution reports a first attempt for the direct quantitative determination of a chemotherapeutic drug in human serum samples by means of Surface Enhanced Raman Spectroscopy (SERS). In this study, SERS substrates constituted by Au nanoparticles deposited on paper by a simple dipping method have been used for rapid (few minutes) analysis of diluted human serum spiked with different concentrations of methotrexate, MTX. The drug concentrations were chosen in a range designed to cover typical therapeutic plasmatic values (from nanomolar to millimolar) in oncological patients, and the pertinent calibration was obtained by Partial Least-Squares Regression (PLSR). Stability selection was employed to evaluate the capability of the PLSR model to accurately predict and extract spectral variations correlated to MTX concentration. Such a quantitative determination is crucial for frequent, and hence adherent, therapeutic drug monitoring, TDM, of chemiotherapic drugs, given their heavy side effects. Its low cost, rapid response and the possibility of obtaining spectra with simple and compact instruments, make SERS particularly apt for implementing effective TDM. The promising results obtained in the analytical validation indicate which steps are to be taken on the way toward a clinical validation with real samples from oncological patients, for MTX as well as for other chemotherapeutic drugs.
authors.affiliation: Department of Engineering and Architecture, University of Trieste, Trieste, Italy. sergo@units.it abonifacio@units.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fornasaro
authors.affiliation: Department of Engineering and Architecture, University of Trieste, Trieste, Italy. sergo@units.it abonifacio@units.it.
authors.forename: Silvia Dalla
authors.initials: SD
authors.lastname: Marta
authors.affiliation: Institute for Maternal and Child Health (I.R.C.C.S.) Burlo Garofolo, UO Pediatric Hemato-Oncology, Trieste, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rabusin
authors.affiliation: Department of Engineering and Architecture, University of Trieste, Trieste, Italy. sergo@units.it abonifacio@units.it.
authors.forename: Alois
authors.initials: A
authors.lastname: Bonifacio
authors.affiliation: Department of Engineering and Architecture, University of Trieste, Trieste, Italy. sergo@units.it abonifacio@units.it.
authors.forename: Valter
authors.initials: V
authors.lastname: Sergo
mesh_terms: D016903:Drug Monitoring / Q000379:methods*; D006046:Gold; D006801:Humans; D053768:Metal Nanoparticles; D008727:Methotrexate / Q000097:blood*; D019095:Point-of-Care Systems; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D006046:Gold; D008727:Methotrexate