A Method Designed for Point-of-care System Monitoring Plasma Concentration of an Anticancer Molecular Targeting Drug with Diamond Electrode
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2022-01-01 |
| Journal | Proceedings for Annual Meeting of The Japanese Pharmacological Society |
| Authors | Takuro Saiki, Genki Ogata, Seishiro Sawamura, Olga Razvina, Kota Watanabe |
| Institutions | Keio University, The University of Osaka |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive Summaryâ- Core Value Proposition: Development of a rapid, low-cost, and compact point-of-care (POC) system for therapeutic drug monitoring (TDM) using an electrochemical approach.
- Material Technology: The system utilizes a simple boron-doped diamond (BDD) plate electrode as the core advanced electrochemical sensing material.
- Target Application: Monitoring the plasma concentration of the anticancer molecular targeting drug, pazopanib (a tyrosine kinase inhibitor).
- Speed and Efficiency: The total procedure, including sample preparation and electrochemical measurement, is completed in approximately 10 minutes, with the measurement itself taking only ~35 seconds.
- Performance Validation: Pharmacokinetic data obtained by the BDD sensor were found to be generally consistent with results derived from the conventional, time-intensive Liquid Chromatography-Mass Spectrometry (LC-MS) method.
- Miniaturization: A palm-sized prototype was successfully fabricated, demonstrating the potential for on-site, tailor-made medicine applications.
- Resource Reduction: The BDD sensor strategy is significantly more compact and inexpensive than traditional LC-MS setups.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| Sensor Material | Boron-Doped Diamond (BDD) | N/A | Advanced electrochemical electrode |
| Electrode Area | ~26 | mm2 | Simple BDD plate configuration |
| Target Analyte | Pazopanib | N/A | Anticancer molecular targeting drug |
| Sample Volume (Plasma) | 100 | ”L | Used for initial concentration determination |
| Sample Volume (Blood) | ~60 | ”L | Successfully analyzed by the prototype system |
| Measurement Time | ~35 | s | Time required for drug concentration determination |
| Total Procedure Time | ~10 | min | Including sample preparation and electrochemical measurement |
| Chemical Modification | None | N/A | Electrode used without chemical surface modification |
| System Size | Palm-sized | N/A | Prototype fabricated for on-site monitoring |
| Validation Standard | LC-MS | N/A | Used to confirm pharmacokinetic data consistency |
Key Methodologies
Section titled âKey MethodologiesâThe study focused on developing and validating a compact electrochemical sensor system for drug monitoring:
- Electrode Selection: A simple boron-doped diamond (BDD) plate electrode (~26 mm2) was selected for its advanced electrochemical properties, requiring no chemical modifications.
- Test Drug Selection: Pazopanib, a tyrosine kinase inhibitor, was chosen as the model anticancer drug for monitoring.
- Initial Plasma Testing: Drug concentration was determined in 100 ”L rat plasma samples that were exogenously mixed with pazopanib.
- Procedure Optimization: All necessary procedures, including sample preparation and electrochemical measurement, were optimized to be completed rapidly (total time ~10 min).
- Pharmacokinetic Evaluation: Pharmacokinetics data obtained using the BDD electrode were compared against data derived from the conventional LC-MS method, showing general consistency.
- In Vivo Application: The system was successfully applied to analyze blood samples collected from healthy rats orally administered pazopanib, as well as plasma samples from eight clinical patients treated with the drug.
- System Miniaturization: A palm-sized prototype system was fabricated, capable of analyzing small volumes (~60 ”L) of rat blood, demonstrating feasibility for on-site use.
Commercial Applications
Section titled âCommercial ApplicationsâThe BDD sensor technology described is highly relevant to several high-growth sectors requiring rapid, decentralized analytical capabilities:
- Therapeutic Drug Monitoring (TDM):
- Enabling rapid, personalized dosing adjustments for molecular targeting drugs (like pazopanib) in oncology.
- Moving TDM from centralized laboratories to the clinical bedside (Point-of-Care).
- Decentralized Diagnostics:
- Development of compact, portable, and inexpensive analytical devices for use in remote clinics or low-resource settings, replacing bulky LC-MS equipment.
- BDD Electrochemical Sensing:
- Applications leveraging the wide potential window and stability of BDD for direct electrochemical detection of complex organic molecules in biological matrices.
- Pharmacokinetic Studies:
- Accelerating preclinical and clinical drug development by providing rapid, real-time pharmacokinetic data with minimal sample volume requirements.
- Tailor-Made Medicine:
- Facilitating the implementation of individualized treatment strategies based on immediate, accurate drug concentration feedback.
View Original Abstract
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 ”L 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 ”L of rat blood. This strategy may contribute to advances in on-site drug monitoring.