Department of Chemistry, University of Waterloo, 200 University Avenue west, Waterloo, ON, CanadaN2L 3G1.
Department of Anaesthesia and Pain Management, Toronto General Hospital, Toronto, ON, Canada M5G 2C4.
Analyst. 2019 Jun 21;144(12):3721-3728. doi: 10.1039/c9an00041k. Epub 2019 Apr 10.
Tranexamic acid (TXA) is an antifibrinolytic used during cardiac surgery that presents high inter-patient variability. High plasma concentrations have been associated with post-operative seizures. Due to the difficulties with maintaining acceptable concentrations of TXA during surgery, implementation of a point-of-care strategy for testing TXA plasma concentration would allow for close monitoring of its concentration during administration. This would facilitate timely corrections to the dosing schedule, and in effect tailor treatment for individual patient needs. In this work, a method for the rapid monitoring of TXA from plasma samples was subsequently carried out via biocompatible solid-phase microextraction (Bio-SPME) coupled directly to tandem mass spectrometry via a microfluidic open interface (MOI). MOI operates under the concept of a flow-isolated desorption volume and was designed with aims to directly hyphenate Bio-SPME to different detection and ionization systems. In addition, it allows the desorption of Bio-SPME fibers in small volumes while it concurrently continues feeding the ESI with a constant flow to minimize cross-talking and instabilities. The methodology was used to monitor six patients with varying degrees of renal dysfunction, at different time points during cardiac surgery. MOI proves to be a reliable and feasible tool for rapid therapeutic drug monitoring. Affording total times of analysis as low as 30 seconds per sample in its high throughput mode configuration while the single sample turn-around time was 15 minutes, including sample preparation. In addition, cross-validation against a standard thin film solid phase microextraction using liquid chromatography coupled to tandem mass spectrometry (TFME-LC-MS/MS) method was performed. Bland-Altman analysis was used to cross-validate the results obtained by the two methods. Data analysis demonstrated that 92% of the compared data pairs (n = 63) were distributed within the acceptable range. The data was also validated by the Passing Bablok regression, demonstrating good statistical agreement between these two methods. Finally, the currently presented method offers comparable results to the conventional liquid chromatography with acceptable RSDs, while only necessitating a fraction of the time. In this way, TXA concentration in plasma can be monitored in a close to real time throughput during surgery.
氨甲环酸（TXA）是一种在心脏手术中使用的抗纤维蛋白溶解剂，患者间的血浆浓度差异很大。高浓度的 TXA 与术后癫痫发作有关。由于在手术过程中难以维持可接受的 TXA 浓度，因此实施即时检测 TXA 血浆浓度的策略可以在给药过程中密切监测其浓度。这将有助于及时调整给药方案，从而根据患者的个体需求进行精准治疗。在这项工作中，随后通过生物相容性固相微萃取（Bio-SPME）结合微流控开放式接口（MOI）直接与串联质谱法，对从血浆样本中快速监测 TXA 进行了研究。MOI 基于流动隔离解吸体积的概念设计，旨在直接将 Bio-SPME 与不同的检测和离子化系统联用。此外，它允许在小体积下解吸 Bio-SPME 纤维，同时通过恒定的流量继续向 ESI 进样，以最大限度地减少串扰和不稳定性。该方法用于监测 6 名肾功能不同的患者，在心脏手术的不同时间点进行监测。MOI 被证明是一种可靠且可行的快速治疗药物监测工具。在高通量模式配置下，每个样品的总分析时间低至 30 秒，而单个样品的周转时间为 15 分钟，包括样品制备。此外，还对使用液相色谱串联质谱法（LC-MS/MS）的标准薄膜固相微萃取（TFME-LC-MS/MS）方法进行了交叉验证。Bland-Altman 分析用于交叉验证两种方法的结果。数据分析表明，92%的比较数据对（n = 63）分布在可接受范围内。这些数据还通过 Passing Bablok 回归进行了验证，表明这两种方法具有良好的统计学一致性。最后，目前提出的方法提供了与传统液相色谱法相当的结果，且接受度良好，同时仅需要传统方法的一小部分时间。通过这种方式，可以在手术过程中以接近实时的高通量监测血浆中的 TXA 浓度。
