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In order to study anesthetic pharmacokinetics and adequately adjust the anaesthesia depth of patients, real-time measurement of the intraoperative exhaled propofol concentration is of significant importance for anaesthetists. Although a series of analytical techniques and methods have been developed for the detection of exhaled propofol, differential mobility spectrometry (DMS) with the advantages of a much smaller instrument, faster response time and cheaper cost shows great potential for the point of care in the operating room. In this paper, a planar DMS was constructed for real-time continuous measurement of trace propofol in exhaled air. The effects of DMS parameters, such as the radio frequency voltage, the drift gas flow rate and the sampling flow rate of exhaled air on the propofol measurement under high humidity conditions were carefully investigated and discussed. Under the optimum experimental conditions, the limit of detection (LOD) for propofol was achieved in ppbv with a linear range of 0.5 to 25 ppbv, both of which meet clinical requirements. Finally, the planar DMS was performed on a patient undergoing thyroidectomy surgery to real-time monitor the intraoperative exhaled propofol, which demonstrated the capability of DMS for sensitive and breath-by-breath continuous measurement of intraoperative trace exhaled propofol.

Humidity as a major issue affects the quantitative performance of ion mobility spectrometry (IMS) in field applications. According to the kinetic equations of ion-molecular reaction, the intensity ratio of the product ion peak (PIP) over the reactant ion peak (RIP) is proposed as a quantitative factor to correct real-time humidity variation. By coupling this method with a unidirectional anisole-assisted photoionization IMS, direct breath-by-breath measurement of intraoperative propofol was achieved for the first time, which provided more clinical information for studying the anesthetics pharmacokinetics. Although the signal intensities of the RIP and the propofol PIP both declined along with the increase of humidity, the intensity ratio of Propofol/(RIP + Propofol) kept almost constant in a wide relative humidity range of 0%-98%, enabling direct quantitation of exhaled propofol with varying humidity. Furthermore, interfering ion peaks resulted from the high concentration humidity and anesthetics in single exhalation were eliminated during the balanced anesthesia as the exhaled sample was diluted by the unidirectional gas flow scheme. As a demonstration, breath-by-breath variation profiles of propofol were obtained via monitoring end-tidal propofol concentration of intraoperative anesthetized patients (n = 7). The analyses were quantitative, corrected for humidity in real-time, without measuring the humidity content of each breath sample during operation, which show potential for the quantitative analysis of other high humidity samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rapid and quantitative determination of blood propofol concentration is important for anesthesiologists to accurately control intraoperative propofol dose, timely monitor physiological statuses of patients and greatly improve the safety of surgery. Herein, a dopant-assisted negative photoionization ion mobility spectrometer with the optimized ionization region structure and the three-way inlet design was developed, increasing the generation ratio of the reactant ions O 2 , and improving the ionization efficiency of propofol molecules. Besides, the addition of methanol-anisole solution during injection promoted the neutral desorption of propofol in blood, further improving the detection sensitivity by an order of magnitude, eliminating any sample pretreatment and effectively reducing the single analysis time to less than 1 min compared to the previous article. The dual calibration quantitative method, i.e. the method of calibrating the O - concentration and the sample concentration changes during the entire process of detecting propofol through the integral value of M·O 2 - , successfully achieved accurate quantification of blood propofol. And the linear calibration curve of propofol was obtained with the range of 0.1-15 ng μL 2 - , which was fulfilled to conduct propofol determination throughout the perioperative period. Finally, this method was applied to clinically measure the blood propofol concentration in patients newly regained consciousness with concentrations ranging from 0.2 ng μL 2 - , and it turned out that the older patient had the lower propofol concentration in blood.-1 and with the limit of detection of 0.03 ng μL -1 , which was fulfilled to conduct propofol determination throughout the perioperative period. Finally, this method was applied to clinically measure the blood propofol concentration in patients newly regained consciousness with concentrations ranging from 0.2 ng μL -1 to 3 ng μL -1 , and it turned out that the older patient had the lower propofol concentration in blood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Online measuring end-tidal propofol concentration during balanced anesthesia is important for anesthetists to learn the patient's anesthesia depth as exhaled propofol concentration is well related to blood propofol concentration. In previous work, exhaled propofol was detected using acetone assisted negative photoionization ion mobility spectrometer, however, the existence of high concentration sevoflurane interfered the response of propofol. In this work, an anisole assisted photoionization ion mobility spectrometer operated in positive mode was developed to sensitively and selectively measure the end-tidal propofol by eliminating the interferences of exhaled humidity and sevoflurane during balanced anesthesia. Anisole molecular ion is stable enough not to go under proton transfer reaction with water presents in the exhaled breath. Hence, the exhaled humidity related peaks were eliminated and only one propofol product ion peak (K 0  = 1.50 cm 2  V -1  s -1 ) was observed. The relative standard deviation (RSD) ranging from 0.64%-0.91% showed good repeatability and the quantitative range was 0.2-40 ppbv with a response time of 4 s. Finally, the performance of the proposed method was demonstrated by monitoring end-tidal propofol of balanced anesthetized patients during gastric cancer surgery., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The concentration of propofol in blood is an important indicator for anesthesiologists to monitor and regulate the anesthesia depth of patients during surgery. Herein, a negative photoionization ion mobility spectrometry with acetone as the dopant was developed for rapid and direct determination of intraoperative blood propofol concentration in the operating theatre. High concentration of acetone molecules in the carrier gas was used not only to enhance neutral desorption and release free propofol molecules from the whole blood, but also to increase the intensity of reactant O 2 - ions simultaneously, which allowed to measure trace propofol in less than 2 min without any tedious pretreatment. Under optimized conditions, a linear calibration curve of propofol was obtained with the range of 0.5-20 ng μL 3 - , which met the clinical requirements and correlated well with standard HPLC methods. Finally, the method was applied to detect intraoperative blood propofol concentration in nearly 100 surgical patients, demonstrating its excellent detection capability and facilitating the study of propofol pharmacokinetics.-1 and with a limit of detection of 0.14 ng μL -1 , which met the clinical requirements and correlated well with standard HPLC methods. Finally, the method was applied to detect intraoperative blood propofol concentration in nearly 100 surgical patients, demonstrating its excellent detection capability and facilitating the study of propofol pharmacokinetics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Online monitoring of end-tidal propofol provides important information of anesthesia deepness for anesthetists as propofol concentrations in plasma and breath are well correlated. In this work, a dopant-assisted photoionization positive ion mobility spectrometry (DAPI-PIMS) coupled with time-resolved purge introduction was developed for online quantitative monitoring end-tidal propofol. With optimized dopant, toluene, the selectivity and sensitivity of propofol was improved as interference from sevoflurane was eliminated. Using the time-resolved purge introduction, the response of propofol and moisture was separated due to their absorption differences on the inwall of the fluorinated ethylene propylene (FEP) sample loop, ensuring sensitive measurement of end-tidal propofol with a short response time of 4 s. The quantitative equation derived from the second order reaction kinetics model extended the quantitative range of propofol from 0.2 ppbv to 45 ppbv. Finally, the method was used to monitor the intraoperative end-tidal propofol of six patients, and the results nicely demonstrated its feasibility in practical clinical environment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Online monitoring of exhaled propofol concentration is important for anesthetists to provide adequate anesthesia as propofol concentrations in plasma and breath are correlated reasonably well. Exhaled propofol could be detected by 63 Ni ion mobility spectrometry in negative ion mode; however, the radioactivity of 63 Ni source restricts its clinical application due to safety, environmental, and regulatory concerns. An acetone-assisted negative photoionization ion mobility spectrometer (AANP-IMS) using a side-mounted vacuum ultraviolet (VUV) lamp in the unidirectional (UD) flow mode was developed for sensitive measurement of exhaled propofol by producing a high percentage of O 2 - (H 2 . An adsorption sampling and time-resolved purge introduction system was developed to eliminate the interference of residual inhaled anesthetic sevoflurane based on their different adsorptions between propofol and sevoflurane on the inwall of the fluorinated ethylene propylene (FEP) sample loop. The effects of the inner diameter and the length of the sample loop on the signal intensity of propofol and the time-resolution between propofol and sevoflurane were theoretically and experimentally investigated. A sample loop with 3 mm i.d. and 150 cm length allowed sensitive measurement of exhaled propofol with a response time of 4 s, a linear response range for propofol was achieved to be 0.2 to 14 ppbv with a limit of detection (LOD) of 60 pptv, and the quantification of propofol was not influenced by the change of the sevoflurane concentration. Finally, the performance of monitoring exhaled propofol during surgery was demonstrated on a patient undergoing laparoscopic distal pancreatectomy combined with cholecystectomy.n . An adsorption sampling and time-resolved purge introduction system was developed to eliminate the interference of residual inhaled anesthetic sevoflurane based on their different adsorptions between propofol and sevoflurane on the inwall of the fluorinated ethylene propylene (FEP) sample loop. The effects of the inner diameter and the length of the sample loop on the signal intensity of propofol and the time-resolution between propofol and sevoflurane were theoretically and experimentally investigated. A sample loop with 3 mm i.d. and 150 cm length allowed sensitive measurement of exhaled propofol with a response time of 4 s, a linear response range for propofol was achieved to be 0.2 to 14 ppbv with a limit of detection (LOD) of 60 pptv, and the quantification of propofol was not influenced by the change of the sevoflurane concentration. Finally, the performance of monitoring exhaled propofol during surgery was demonstrated on a patient undergoing laparoscopic distal pancreatectomy combined with cholecystectomy.

The plasma propofol concentration is important information for anaesthetists to monitor and adjust the anaesthesia depth for patients during a surgery operation. In this paper, a stand-alone ion mobility spectrometer (IMS) was constructed for the rapid measurement of the plasma propofol concentrations. Without any sample pre-treatment, the plasma samples were dropped on a piece of glass microfiber paper and then introduced into the IMS cell by the thermal desorption directly. Each individual measurement could be accomplished within 1 min. For the plasma propofol concentrations from 1 to 12 μg mL -1 , the IMS response was linear with a correlation coefficient R 2 of 0.998, while the limit of detection was evaluated to be 0.1 μg mL -1 . These measurement results did meet the clinical application requirements. Furthermore, other clinically-often-used drugs, including remifentanil, flurbiprofen and atracurium, were found no significant interference with the qualitative and quantitative analysis of the plasma propofol. The plasma propofol concentrations measured by IMS were correlated well with those measured by the high performance liquid chromatography (HPLC). The results confirmed an excellent agreement between these two methods. Finally, this method was applied to monitor the plasma propofol concentrations for a patient undergoing surgery, demonstrating its capability of anaesthesia monitoring in real clinical environments.

Based on the adsorption of analytes in the sampling loop, a time-resolved dynamic dilution introduction method was developed for negative ion mobility spectrometry to continuously monitor end-tidal propofol without other sample pre-separation. The dynamic dilution characteristics of propofol and moisture in the Teflon sample loop (4 mm o.d. and 2.4 mm i.d., 150 cm length) were both theoretically and experimentally investigated. The prominent absorption differences between propofol and moisture on the inwall of the sample loop allowed their concentrations to be time-resolved during the injection process, realizing sensitive measurement of end-tidal propofol with a response time of 2 s. At the optimized carrier gas flow rate of 700 mL min(-1), the linear response range for propofol was achieved to be 0.2 to 20 ppbv with a limit of detection (LOD) of 65 pptv. Finally, this method was performed on a patient undergoing mastectomy surgery to continuously monitor the end-tidal propofol with an interval of five respirations and the result nicely demonstrated its fast response to the propofol changes.

On-line monitoring of propofol in exhaled air is a potential way to evaluate the anaesthesia depth for patients during surgery. In this study, a negative (63)Ni ionization high resolution ion mobility spectrometer with Bradbury-Nielsen-Gate-Grid structure was built to measure propofol with reactant ions Cl(-)(H2O) n using dichloromethane as dopant. Instead of forming three propofol ions (M - H)(-), M · O2(-), and (M2 - H)(-) with reactant ions O2(-)(H2O)n, only product ion M · Cl(-) was produced when introducing dichloromethane gas. The peak-to-peak resolution (R p-p) between reactant ions Cl(-)(H2O)n and product ion M · Cl(-) was 17.4, which was 1.6 times larger than that between O2(-)(H2O)n and product ion. Furthermore, the linear response range using reactant ions Cl(-)(H2O)n was 3.5 times wider than that obtained with reactant ions O2(-)(H2O)n.

The concentration of propofol in patient's exhaled air is an indicator of the anesthetic depth. In the present study, a membrane inlet ion mobility spectrometer (MI-IMS) was built for the on-line measurement of propofol. Compared with the direct sample introduction, the membrane inlet could eliminate the interference of moisture and improve the selectivity of propofol. Effects of membrane temperature and carrier gas flow rate on the sensitivity and response time have been investigated experimentally and theoretically. Under the optimized experimental conditions of membrane temperature 100 °C and carrier gas flow rate 200 mL min(-1), the calculated limit of detection (LOD) for propofol was 1 ppbv, and the calibration curve was linear in the range of 10-83 ppbv with a correlation coefficient (R(2)) of 0.993. Finally, the propofol concentration in an anaesthetized mouse exhaled air was monitored continuously to demonstrate the capability of MI-IMS in the on-line measurement of propofol in real samples., (Copyright © 2012 Elsevier B.V. All rights reserved.)