Department of Electrical Engineering and Electronics, University of Liverpool, Brownlow Hill, Liverpool, L69 3GJ, UK.
Department of Chemistry and Biochemistry, Ohio State University, Columbus, OH, USA.
Sci Rep. 2022 Aug 22;12(1):14308. doi: 10.1038/s41598-022-18365-8.
Accurate quantification of blood creatinine is important to estimate the glomerular filtration rate. Existing techniques using liquid chromatography tandem mass spectrometry (LC-MS/MS) have a high accuracy and eliminate most interferences encountered in routine enzymatic and Jaffé methods. However, they require laborious and time-consuming sample treatment and data acquisition. The aim of this study is to develop a fast and simple method to enable a direct analysis of whole blood creatinine with performance measures that are comparable to conventional LC-MS/MS. 5μL whole blood is formed as a three-dimensional spheroid on hydrophobic silanized paper substrates which then undergoes paper-spray ionization-tandem mass spectrometry (PSI-MS/MS). The method is validated using real human samples and compared with LC-MS/MS. PSI-MS/MS whole blood analysis exhibited a lower limit of quantification of 2.5 μg/mL, precision ≤ 6.3%, recovery in the range of 88-94% and excellent linearity (R > 0.99; 2.5-20 μg/mL) covering the normal range for creatinine levels. Creatinine levels were comparable to those measured by LC-MS/MS with small deviations of less than 0.3 μg/mL. This simple, fast and accurate microsampling technique for direct analysis of creatinine from whole blood shows promise for routine clinical screening and monitoring. This approach can be readily extended for other analytes of interest and, due to inherent advantages relating to cost, storability, speed, and simplicity, it can be especially advantageous for use in resource-limited settings.
准确测定血肌酐对于估计肾小球滤过率非常重要。现有的使用液相色谱串联质谱（LC-MS/MS）的技术具有很高的准确性，并消除了常规酶法和 Jaffé 法中遇到的大多数干扰。然而，它们需要繁琐且耗时的样品处理和数据采集。本研究旨在开发一种快速简单的方法，能够直接分析全血肌酐，并具有与传统 LC-MS/MS 相媲美的性能指标。5μL 全血在疏水硅烷化纸基质上形成三维球体，然后进行纸喷雾电离串联质谱（PSI-MS/MS）分析。该方法使用真实的人体样本进行验证，并与 LC-MS/MS 进行比较。PSI-MS/MS 全血分析的定量下限为 2.5μg/mL，精密度≤6.3%，回收率在 88-94%范围内，线性度极好（R>0.99；2.5-20μg/mL），涵盖了肌酐水平的正常范围。肌酐水平与 LC-MS/MS 测量的水平相当，偏差小于 0.3μg/mL。这种简单、快速、准确的从全血中直接分析肌酐的微采样技术有望用于常规临床筛查和监测。这种方法可以很容易地扩展到其他感兴趣的分析物，并且由于与成本、存储性、速度和简单性相关的固有优势，它在资源有限的环境中特别有利。
