Therapeutic drug monitoring of methotrexate with surface-enhanced Raman spectroscopy (SERS)

Description

Methotrexate (MTX) is a key drug in treating several cancers, such as childhood acute lymphoblastic leukaemia. However, its safe use requires therapeutic drug monitoring (TDM) to follow MTX clearance and thereby avoid delayed elimination toxicity by administering a proper dose of MTX rescue drug. Patients are usually followed until MTX concentration falls below 0.2 µM [1]. Current standard analytical methods for MTX quantification rely on immunoassays or chromatographic techniques, which cannot be afforded by every clinic. This entails delayed response time due to sample shipment to reference labs and has stepped up research on affordable and fast alternative techniques for MTX quantification. Surface-enhanced Raman spectroscopy (SERS) is a promising choice given its short time-to-answer and versatility.

This work presents a dual strategy, based on SERS detection, to monitor MTX levels in serum samples of patients receiving high-dose MTX therapy.
On the one hand, nanopillar-assisted separation (NPAS) was applied before SERS detection and enabled MTX quantification in the 5 – 150 µM concentration range [2]. In NPAS, the nanopillars of the SERS substrate function as a sieve or filter, by trapping large molecules such as proteins. As a result, sample handling is kept to a minimum, i.e. serum mixing with an organic solvent.
On the other hand, applying well-defined electric potentials to the SERS substrates resulted in electrochemically assisted SERS, which allowed for MTX attraction and pre-concentration on the SERS substrates. Combined with an appropriate sample preparation, namely gel filtration, electrochemically assisted SERS could be used to quantify MTX in the low concentration range (0.5 – 5 µM) [3].
In both cases, the analysis time was short (< 30 min). Moreover, the SERS detection could be conducted on a portable Raman spectrometer, paving the way for point-of-need monitoring of MTX.

1. A. Paci, G. Veal, C. Bardin, D. Levêque, N. Widmer, J. Beijnen, A. Astier, E. Chatelut, Review of Therapeutic Drug Monitoring of Anticancer Drugs Part 1 - Cytotoxics. Eur. J. Cancer 50 (2014) 2010-2019.
2. Y. Göksel, K. Zor, T. Rindzevicius, B. Als-Nielsen, K. Schmiegelow, A. Boisen, Quantification of methotrexate in human serum using Surface-Enhanced Raman Scattering - Toward therapeutic drug monitoring, ACS Sens. 6 (2021) 2664-2673.
3. Y. Göksel, E. Dumont, R. Slipets, S. Rajendran, S. Sarikaya, L. Thamdrup, K. Schmiegelow, T. Rindzevicius, K. Zor, A. Boisen, Methotrexate detection in serum at clinically relevant levels with electrochemically assisted SERS on a benchtop, custom built Raman spectrometer, ACS Sens. 7 (2022) 2358-2369.

Period	29 Aug 2023
Event title	12th International Conference on Advanced Vibrational Spectroscopy
Event type	Conference
Location	Krakow, PolandShow on map
Degree of Recognition	International