A rapid and simple electrochemical detection of the free drug concentration in human serum using boron-doped diamond electrodes
A rapid and simple electrochemical detection of the free drug concentration in human serum using boron-doped diamond electrodes
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DOI：
10.1039/d2an01037b
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发表时间：
2022-09-13
期刊：
影响因子：
4.2
通讯作者：
Einaga, Yasuaki
中科院分区：
文献类型：
--
作者：
Moriyama, Hideto;Ogata, Genki;Einaga, Yasuaki
监测血液中的药物浓度并将其反映在剂量中对于安全有效的药物治疗至关重要。大多数药物测定是基于血清中结合和未结合蛋白质的总浓度，尽管只有未结合浓度会引起有益和不良事件。预计单独监测未结合浓度可提供进一步优化药物治疗的方法。然而，由于常规方法的分析时间长和成本高，未结合浓度监测尚未常规用于药物治疗。在这里，我们已经开发了一种快速的电化学方法来确定在超滤的人血清中使用掺硼金刚石（BDD）电极的未结合浓度。当抗癌药物多柔比星被用作测试药物时，多柔比星介导的溶解氧的催化还原提供了灵敏的电化学信号，检测限为0.14 nM。相反，在相同条件下，由于溶解氧还原电流的干扰，玻璃碳（GC）的灵敏度较差。BDD和GC的信号背景比（S/B）分别为11.5（10 nM阿霉素）和1.1（50 nM）。结果表明，在临床浓度范围内，10秒内的快速测量时间是可能的。此外，在超滤的人血清中，获得的未结合阿霉素浓度值与通过常规液相色谱-质谱法定量的值显示出良好的一致性。这种方法具有在临床环境中应用的潜力，其中快速和简单的分析方法将是有益的。
Monitoring drug concentration in blood and reflecting this in the dosage are crucial for safe and effective drug treatment. Most drug assays are based on total concentrations of bound and unbound proteins in the serum, although only the unbound concentration causes beneficial and adverse events. Monitoring the unbound concentration alone is expected to provide a means for further optimisation of drug treatment. However, unbound concentration monitoring has not been routinely used for drug treatment due to the long analysis time and the high cost of conventional methods. Here, we have developed a rapid electrochemical method to determine the unbound concentration in ultrafiltered human serum using boron-doped diamond (BDD) electrodes. When the anticancer drug doxorubicin was used as the test drug, the catalytic doxorubicin-mediated reduction of dissolved oxygen provided a sensitive electrochemical signal, with a detection limit of 0.14 nM. In contrast, the sensitivity of glassy carbon (GC) was inferior under the same conditions due to interference from the dissolved oxygen reduction current. The signal background ratio (S/B) of BDD and GC was 11.5 (10 nM doxorubicin) and 1.1 (50 nM), respectively. The results show that a fast measurement time within ten seconds is possible in the clinical concentration range. Additionally, in the ultrafiltered human serum, the obtained values of unbound doxorubicin concentration showed good agreement with those quantified by conventional liquid chromatography-mass spectrometry. This approach has the potential for application in clinical settings where rapid and simple analysis methods would be beneficial.