Low-concentration measurement of pharmaceutical analytes using droplet evaporation Raman spectroscopy for therapeutic drug monitoring

Sora Tomita; Terumasa Ito; Kazuyuki Iwaikawa; Gen Hayase; Daisuke Yoshino; Kazuhiko Misawa

doi:10.1117/12.2609490

7 March 2022 Low-concentration measurement of pharmaceutical analytes using droplet evaporation Raman spectroscopy for therapeutic drug monitoring

Sora Tomita, Terumasa Ito, Kazuyuki Iwaikawa, Gen Hayase, Daisuke Yoshino, Kazuhiko Misawa

Author Affiliations +

Proceedings Volume PC11957, Biomedical Vibrational Spectroscopy 2022: Advances in Research and Industry; PC1195713 (2022) https://doi.org/10.1117/12.2609490
Event: SPIE BiOS, 2022, San Francisco, California, United States

Conference Poster

Abstract

Therapeutic drug monitoring (TDM) is required for an optimal treatment plan to control the dosage of high-risk drugs by monitoring their blood concentration. Currently, a combination of liquid chromatography and tandem mass spectrometry is used for TDM. However, this method requires expertise and skills in sample pretreatment and is not available in all hospitals. Raman spectroscopy allows us to quantify substances in biological samples with only simple pretreatment. Two methods have been reported for detecting low-concentration substances using Raman spectroscopy: surface-enhanced Raman spectroscopy and drop coating deposition Raman spectroscopy. However, it is difficult to quantify the concentration by these methods because the Raman spectra are measured in a dry state. Here, we present a new method to quantify low-concentration pharmaceutical analytes using droplet evaporation Raman spectroscopy. Methotrexate (MTX), one of the immunosuppressive drugs, is reported to cause adverse effects above 10 μM of its blood concentration 24 hours after administration. To quantify low-concentration MTX, we drop the solution onto a superhydrophobic substrate, and simultaneously measure the Raman spectra and the volume of the droplets before completely dried. In particular, we control the evaporation rate of the droplets in a humidified environment, allowing Raman measurements with sufficient exposure time. The initial concentration of the solution is determined from the measured drug concentration during evaporation and the concentration ratio obtained from the volume measurement. Using the new method, we can quantify the concentration of MTX at 50 μM, which is in the order of magnitude required for clinical use.

Citation Download Citation

Sora Tomita, Terumasa Ito, Kazuyuki Iwaikawa, Gen Hayase, Daisuke Yoshino, and Kazuhiko Misawa "Low-concentration measurement of pharmaceutical analytes using droplet evaporation Raman spectroscopy for therapeutic drug monitoring", Proc. SPIE PC11957, Biomedical Vibrational Spectroscopy 2022: Advances in Research and Industry, PC1195713 (7 March 2022); https://doi.org/10.1117/12.2609490

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