Safety Measurement Institute, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Korea.
Department of Nano Science, University of Science and Technology (UST), Daejeon 34113, Korea.
ACS Nano. 2021 Jun 22;15(6):10141-10152. doi: 10.1021/acsnano.1c02016. Epub 2021 Jun 7.
For organ transplantation patients, the therapeutic drug monitoring (TDM) of immunosuppressive drugs is essential to prevent the toxicity or rejection of the organ. Currently, TDM is done by immunoassays or liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods; however, these methods lack specificity or are expensive, require high levels of skill, and offer limited sample throughput. Although matrix-assisted (MA) laser desorption ionization (LDI) mass spectrometry (MS) can provide enhanced throughput and cost-effectiveness, its application in TDM is limited due to the limitations of the matrixes such as a lack of sensitivity and reproducibility. Here, we present an alternative quantification method for the TDM of the immunosuppressive drugs in the blood of organ transplant patients by utilizing laser desorption ionization mass spectrometry (LDI-MS) based on a tungsten disulfide nanosheet, which is well-known for its excellent physicochemical properties such as a strong UV absorbance and high electron mobility. By adopting a microliquid inkjet printing system, a high-throughput analysis of the blood samples with enhanced sensitivity and reproducibility was achieved. Furthermore, up to 80 cases of patient samples were analyzed and the results were compared with those of LC-MS/MS by using Passing-Bablok regression and Bland-Altman analysis to demonstrate that our LDI-MS platform is suitable to replace current TDM techniques. Our approach will facilitate the rapid accurate analysis of blood samples from a large number of patients for immunosuppressive drug prescriptions.
对于器官移植患者，免疫抑制药物的治疗药物监测（TDM）对于防止器官毒性或排斥至关重要。目前，TDM 是通过免疫测定或液相色谱-串联质谱（LC-MS/MS）方法进行的；然而，这些方法缺乏特异性或昂贵，需要高水平的技能，并且提供的样品通量有限。尽管基质辅助（MA）激光解吸电离（LDI）质谱（MS）可以提供增强的吞吐量和成本效益，但由于基质的局限性，如缺乏灵敏度和重现性，其在 TDM 中的应用受到限制。在这里，我们提出了一种替代的定量方法，用于通过基于二硫化钨纳米片的激光解吸电离质谱（LDI-MS）来检测器官移植患者血液中的免疫抑制药物的 TDM，二硫化钨纳米片因其优异的物理化学性质而闻名，例如强的紫外吸收和高电子迁移率。通过采用微液喷墨打印系统，实现了具有增强的灵敏度和重现性的高通量血液样本分析。此外，通过使用 Passing-Bablok 回归和 Bland-Altman 分析，对多达 80 例患者样本进行了分析，并将结果与 LC-MS/MS 进行了比较，证明我们的 LDI-MS 平台适合替代当前的 TDM 技术。我们的方法将有助于快速准确地分析大量患者的血液样本，以制定免疫抑制药物处方。
