A Method Designed for Point-of-care System Monitoring Plasma Concentration of an Anticancer Molecular Targeting Drug with Diamond Electrode

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  • Takuro Saiki
    Department of Medical Oncology, Niigata Univ
  • Ogata Genki
    Division of Glocal Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University Department of Chemistry, Keio University
  • Sawamura Seishiro
    Division of Glocal Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University
  • Razvina Olga
    Niigata University School of Medicine
  • Watanabe Kota
    Niigata University School of Medicine
  • Kato Rito
    Niigata University School of Medicine
  • Asai Kai
    Department of Chemistry, Keio University
  • Matsumoto Yoshifumi
    Department of Medical Oncology, Niigata Univ
  • Moriyama Masato
    Department of Medical Oncology, Niigata Univ
  • Saijo Yasuo
    Department of Medical Oncology, Niigata Univ
  • Einaga Yasuaki
    Department of Chemistry, Keio University
  • Hibino Hiroshi
    Division of Glocal Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University

Description

<p>Measurement of plasma drug concentrations at a clinical site is essential for personalized medicine. For such purpose, the conventional liquid chromatography-mass spectrometry (LC-MS) method is unlikely to be suitable, owing to time and cost consumption. In this study, we describe an approach to rapid, easy, and low-cost drug monitoring with a boron-doped diamond (BDD) electrode, an advanced electrochemical material. As a test drug, we selected pazopanib, an inhibitor for multiple tyrosine kinase types. A small size sensor system with a simple BDD plate electrode of ~26 mm2 without any chemical modifications determined the drug concentration in a measurement time of ~35 s from 100 µL rat plasma, which was exogenously mixed with pazopanib. We showed that this system was also applicable to blood samples collected from healthy rats orally administrated with pazopanib as well as drug-treated patients with different cancer types. Notably, all the procedures, including sample preparation and electrochemical measurement, were completed in a short time of ~10 min. The pharmacokinetics data obtained by the BDD electrode were similar to the data determined by LC-MS. Finally, we fabricated a prototype of a palm-sized system, which successfully analyzed ~60 µL of rat blood. This strategy may contribute to advances in on-site drug monitoring.</p><p>Based on them, we evaluated plasma samples from five rats orally administered pazopanib and eight clinical patients treated with the drug at our institution. The plasma concentrations and other pharmacokinetic parameters obtained by the BDD method were generally consistent with the LC-MS.</p><p>Because this strategy by the BDD sensor is more compact and inexpensive than the LC-MS setup, the electrochemical approach described here can be commonly used and contribute to tailor-made medicine.</p>

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