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Protocol for Therapeutic Drug Monitoring Within the Clinical Range Using Mid-infrared Spectroscopy
Analytical Chemistry ( IF 6.7 ) Pub Date : 2024-11-18 , DOI: 10.1021/acs.analchem.4c03864
Pin Dong, Kezheng Li, David J. Rowe, Thomas F. Krauss, Yue Wang

Therapeutic drug monitoring (TDM), which involves measuring drug levels in patients’ body fluids, is an important procedure in clinical practice. However, the analysis technique currently used, i.e. liquid chromatography–tandem mass spectrometry (LC–MS/MS), is laboratory-based, so does not offer the short response time that is often required by clinicians. We suggest that techniques based on Fourier transform infrared spectroscopy (FTIR) offer a promising alternative for TDM. FTIR is rapid, highly specific and can be miniaturized for near-patient applications. The challenge, however, is that FTIR for TDM is limited by the strong mid-IR absorption of endogenous serum constituents. Here, we address this issue and introduce a versatile approach for removing the background of serum lipids, proteins and small water-soluble substances. Using phenytoin, an antiepileptic drug, as an example, we show that our approach enables FTIR to precisely quantify drug molecules in human serum at clinically relevant levels (10 μg/mL), providing an efficient analysis method for TDM. Beyond mid-IR spectroscopy, our study is applicable to other drug sensing techniques that suffer from the large background of serum samples.

中文翻译:


使用中红外光谱法在临床范围内监测治疗药物的方案



治疗药物监测 (TDM) 涉及测量患者体液中的药物水平,是临床实践中的一项重要程序。然而,目前使用的分析技术,即液相色谱-串联质谱 (LC-MS/MS),是基于实验室的,因此无法提供临床医生通常要求的短响应时间。我们建议基于傅里叶变换红外光谱 (FTIR) 的技术为 TDM 提供了一种有前途的替代方案。FTIR 快速、高特异性,可小型化用于近患者应用。然而,挑战在于,用于 TDM 的 FTIR 受到内源性血清成分的强中红外吸收的限制。在这里,我们解决了这个问题,并介绍了一种去除血清脂质、蛋白质和水溶性小物质背景的通用方法。以抗癫痫药物苯妥英钠为例,我们表明我们的方法使 FTIR 能够精确量化人血清中临床相关水平 (10 μg/mL) 的药物分子,为 TDM 提供了一种有效的分析方法。除了中红外光谱之外,我们的研究还适用于其他受血清样品大背景影响的药物传感技术。
更新日期:2024-11-19
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