MSACL 2025 Abstract

Nanosheet-Assisted LDI-ToF Studies for Therapeutic Drug Monitoring of Human Blood Samples

Tae Geol Lee (1), Sunho Joh (1), Jaekak Yoo (1), Hee-Kyung Na (1), Jin Gyeong Son (1), Seungmi Lee (1), Mun Seok Jeong (2), Sang-Guk Lee (3), Jeong Hee Moon (4)
(1) Korea Research Institute of Standards and Science (KRISS), Daejeon, Korea (2) Hanyang University, Seoul Korea (3) Yonsei University College of Medicine, Seoul, Korea (4) Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea

Tae Geol Lee, PhD (Presenter) Korea Research Institute of Standards and Science

Presenter Bio: ❙Education❙
1995 PhD in Physical Chemistry, Seoul National University
1991 MS in Physical Chemistry, Seoul National University
1989 BS in Chemistry, Seoul National University

❙Professional Training❙
2001 ~ Principal Researcher in KRISS
2000 ~ 2001 Senior Researcher in Nortel Networks, Canada
1996 ~ 2000 Postdoctoral Researcher in Department of Chemistry, University of Toronto
1995 ~ 1996 Postdoctoral Researcher in Department of Chemistry, Seoul National University

❙Awards and Honors❙
2016 Ministry of Science and Technology Award
2016 Prime Minister Award

Relevant Financial Disclosures (within past 24 months, reported on Mar 18, 2025) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

INTRODUCTION:
Two-dimensionally layered transition metal dichalcogenides (TMDs) have been widely used in various biomedical applications such as biosensing and cancer therapy due to their characteristics including UV absorbance, photoinduced thermal effect, tunable bandgap and photoluminescence [1]. However, their applications in therapeutic drug monitoring, which is essential for individualizing drug dosage regimens, is rarely reported.

METHODS:
A facile platform for rapid quantitative determination was fabricated via inkjet printing of TMD exfoliates and the concentrations of therapeutic drug in the patient blood sample were analyzed by using laser desorption/ionization time-of-flight (LDI-ToF) method.

RESULTS:
In this work, we report that chemically exfoliated TMD nanosheets including tungsten disulfide (WS2), tungsten ditelluride (WTe2) and molybdenum ditelluride (MoTe2) are suitable for therapeutic drug monitoring based on laser desorption/ionization mass spectrometry (LDI-MS). The WS2 nanosheets allowed for sensitive detection of commonly prescribed immunosuppressive drugs including cyclosporine A and tacrolimus [2]. Quantification of antiepileptic drugs in human blood was achieved using WTe2 and MoTe2 nanosheets, while they also facilitated the concentration determination of vitamin D3 [3]. Computational investigation using density function theory further elucidated that desorption can be facilitated by electrostatic repulsion between positively charged analytes and holes generated on the substrate surface upon laser irradiation (i.e., charge-driven desorption).

CONCLUSION:
Employing TMDs as matrices in LDI-MS enhances the sensitivity of quantitative drug and biomarker analysis, even at low concentrations. The process benefits from improved reproducibility through inkjet printing and is supported by the statistical analysis for method agreement. The compatibility of LDI-MS with LC-MS/MS techniques will facilitates the broader adoption in clinical diagnostics. The DFT calculations allowed for estimation of potential protonation sites for various drugs, where the electronic interaction between the TMD nanosheets can be critical. It is expected that the influence of the properties of TMD in LDI mechanism can be elucidated by incorporating the drugs and the TMDs into a single system so that the interactions during the ionization process can estimated.

REFERENCES:
[1] Agarwal, V., et al., Recent advances in the field of transition metal dichalcogenides for biomedical applications. Nanoscale, 2018. 10: p. 16365-16397.
[2] Joh, S., et.al., Quantitative analysis of immunosuppressive drugs using tungsten disulfide nanosheet-assisted laser desorption ionization mass spectrometry. ACS Nano, 2021. 15: p. 10141-10152.
[3] Joh, S., et al., Role of chalcogenides in sensitive therapeutic drug monitoring using laser desorption and ionization. ACS Nano, 2024. 18: p. 17681-17693.