实时定量测量呼出气中痕量麻醉剂的离子迁移谱方法研究

The concentration of exhaled anesthetic is closely related to its concentration in blood. It is of significant clinical significance for the implementation of accurate anesthesia to develop real-time quantitative analysis method for the determination of exhaled trace anesthetic. Intravenous anesthetic propofol and inhaled anesthetic sevoflurane are commonly used in balanced anesthesia. With the advantages of rapid and sensitive, ion mobility spectrometry has been used for the determination of exhaled anesthetic. But it faces the problems of the influence of high humidity, complex components, and high concentration of sevoflurane on real-time quantitative determination of trace propofol. Based on the bipolar photoionization ion mobility spectrometry, this application aims to achieve highly selective detection of propofol and sevoflurane in positive and negative modes respectively by optimizing and screening reagent molecules. With the real-time dynamic dilution injection technique, the exhaled breath was dynamic diluted in the unidirectional flow mode, so as to reduce the influence of humidity. Fluent simulation and experiment guide the structural improvement design of the reaction zone to improve the sensitivity of the measurement. Based on the second-order reaction kinetic equation, a theoretical quantitative model under the condition of changeable reagent ion intensity will be established by using the ratio of product ion to reagent ion intensity, so as to improve the accuracy and robustness of the quantitative analysis. The established analytical method will be applied to the detection of exhaled anesthetics in balanced anesthesia, to verify its feasibility and applicability, and to provide a new research method for clinical accurate anesthesia.

呼出气麻醉剂浓度与麻醉剂的血药浓度密切相关，发展实时定量测量呼出气中痕量麻醉剂的分析方法，对实施精准麻醉具有重要的临床意义。复合麻醉中常用的有静脉麻醉剂丙泊酚和吸入式麻醉剂七氟烷。离子迁移谱测量呼出气麻醉剂具有快速、灵敏等优点，但是面临高湿度、复杂组分以及高浓度七氟烷影响痕量丙泊酚实时定量的问题。本申请拟基于正负双模式的光电离离子迁移谱，通过优化和筛选试剂分子，在正负模式下分别实现丙泊酚和七氟烷的选择性测量；采用实时动态稀释进样技术，在单向气流模式下对呼出气样品进行动态稀释，降低湿度的影响，通过fluent模拟和实验指导反应区结构改进设计，提高测量的灵敏度；基于二级反应动力学方程，利用产物离子和试剂离子强度比值，建立试剂离子强度波动状态下的理论定量模型，提升实时定量的准确性和稳健性。将建立的分析方法应用到复合麻醉中呼出气麻醉剂的检测，验证其可行性和适用性，为临床精准麻醉提供新的研究方法。

呼出气中麻醉剂浓度与其血药浓度密切相关，实时定量测量呼出气中痕量麻醉剂的分析方法，对实施精准麻醉具有重要的临床意义。离子迁移谱测量呼出气麻醉剂具有快速、灵敏等优点，但是面临高湿度、复杂组分以及高浓度七氟烷影响痕量丙泊酚实时定量的问题。本研究基于试剂辅助光电离离子迁移谱，通过优化和筛选试剂分子苯甲醚，在正离子模式下实现了复合麻醉高浓度七氟烷下痕量丙泊酚的高选择性测量；通过实时动态稀释进样技术，在单向气流模式下对呼出气样品进行动态稀释，降低了湿度的影响，丙泊酚检测的灵敏度达到pptv量级，响应时间75ms；基于二级反应动力学方程，利用产物离子和试剂离子的强度比值作为定量因子，建立了试剂离子强度波动状态下以及呼出气湿度变化状态下的理论定量模型，提升了定量的准确性和稳健性，实现了术中呼出气痕量丙泊酚的实时定量监测（0.2-40ppbv），为麻醉药代动力学研究提供了更多的临床信息，同时为临床精准麻醉提供了新的研究方法。