A method for increasing the response speed of continuous monitoring of humidified propofol gas

Abstract

The present application belongs to the technical field of chemical analysis and detection, and particularly relates to a method for improving the response speed of continuous monitoring of humidified propofol gas. The disclosed technical solution is characterized in that the sampling system and the gas transmission system are optimized in coordination. In the analysis mode, the flow meter (1) and the air suction pump are continuously operated to extract humidified propofol gas for sample analysis. In the cleaning mode, the flow meter (1) and the air suction pump are continuously operated, the flow meter (2) extracts clean air, the cleaning flow rate is controlled to be greater than the sample flow rate, the sample analysis is performed, and the heat tracing pipe and the buffer tank are cleaned. The monitoring is performed according to the analysis mode-cleaning mode-analysis mode switching, the rapid analysis and rapid cleaning are realized, the propofol adsorption and residue are reduced, the T90 and T10 of the system are significantly shortened, and the effects of continuous monitoring and rapid response are achieved.

Description

Technical Field

[0001] This invention belongs to the field of chemical analysis and detection technology, specifically relating to a method for improving the response speed of continuous monitoring of humidified propofol gas. Background Technology

[0002] Currently, propofol is the most widely used intravenous anesthetic in clinical practice. Its milky-white appearance has earned it the nickname "anesthetic milk." It primarily works by enhancing the function of the inhibitory neurotransmitter GABA in the central nervous system, thereby producing general anesthesia and sedation. After intravenous injection, the drug quickly enters the brain and takes effect, with an onset time of only 30-60 seconds. The drug is metabolized and eliminated from the body very rapidly, resulting in rapid recovery of consciousness and high-quality awakening after discontinuation. Propofol's rapid distribution half-life of only 2-4 minutes means that its blood concentration reaches its peak quickly and then declines rapidly after administration, directly causing dramatic fluctuations in the depth of anesthesia within a short period. The depth of anesthesia is directly related to its concentration at the effect site, while the effect site concentration is driven by the blood concentration; therefore, real-time monitoring is crucial for achieving precise anesthesia.

[0003] Because exhaled propofol concentration accurately reflects blood drug concentration, non-invasive breath-based monitoring is becoming a research hotspot. Among these technologies, ion mobility spectrometry (IMS) is widely recognized as the most clinically valuable real-time propofol monitoring technology due to its ppb-level sensitivity, sub-second response time, and miniaturization advantages. However, despite its theoretically rapid response capability, IMS's actual response speed in clinical propofol monitoring applications falls far short of expectations, primarily due to the following three issues:

[0004] 1. Response lag: The actual T90 (90% saturation response time) is often greater than 10 seconds, far from the theoretical level of <1 second, making it difficult to track pharmacokinetic changes in real time, and there is a delay in anesthesia regulation.

[0005] 2. Slow recovery: The actual T10 (time to drop to 10% of baseline) often exceeds 1 minute. When patients are awake or being tested alternately, residual propofol can cause cross-contamination and interfere with subsequent measurements.

[0006] 3. One-sided optimization: Existing technologies only focus on improving the performance of local modules such as ionization sources and migration tubes, ignoring the limitations of the sampling and gas transmission system on response speed, and lacking systematic optimization of the entire "sampling-transmission-detection" chain.

[0007] CN109781827A discloses a positive ion mobility spectrometry method for detecting propofol in exhaled breath. This method uses a time-resolved dynamic dilution injection device and reagent molecule-assisted photoionization positive ion mobility spectrometry to eliminate the influence of sevoflurane and humidity in exhaled breath during combined anesthesia, and realizes continuous online clinical monitoring of propofol molecules in exhaled breath. However, this method does not disclose the monitoring process parameters of the response time T90 and recovery time T10 of propofol concentration from 3 ppb to blank.

[0008] CN111220683A discloses a method for real-time online monitoring of exhaled propofol. It employs a flowmeter-controlled sampling pump for negative pressure sampling, uses anisole as a dopant, and places three vacuum ultraviolet lamps on the upper, lower, and left sides of the reaction zone to detect exhaled propofol under high humidity conditions. This improves the real-time ionization efficiency of propofol and allows for continuous online simultaneous monitoring of propofol and sevoflurane in the terminal exhaled breath of patients undergoing total intravenous anesthesia. However, this method does not disclose the parameters of response time T90 and recovery time T10 during continuous monitoring.

[0009] CN112924527A discloses a method for improving the sensitivity of exhaled propofol detection. It employs a low-temperature enrichment and high-temperature thermal desorption membrane sampling method, utilizing the hydrophobicity and selective permeability of the PDMS membrane to effectively eliminate the influence of humidity in exhaled breath. Through semiconductor-cooled low-temperature enrichment sampling and high-temperature thermal desorption membrane sampling, the sensitivity of exhaled propofol detection is improved to the ppbv level. This method only discloses the response time and recovery time for a single sample injection analysis; it does not disclose the impact of high and low concentration changes on the monitoring speed of humidified propofol gas.

[0010] To address the aforementioned deficiencies in the prior art, the core objective of this invention is to provide a method for improving the response speed of propofol gas monitoring. By synergistically optimizing the sampling system and the gas transmission system, the T90 and T10 of the system are significantly shortened, enabling real-time and accurate monitoring of propofol concentration to meet the stringent requirements of clinical anesthesia. Summary of the Invention

[0011] To address the aforementioned technical problems, this invention provides a method for improving the response speed of continuous monitoring of humidified propofol gas, enabling rapid analysis and cleaning, reducing propofol adsorption and residue, and achieving the effects of continuous monitoring and rapid response.

[0012] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows: A method to improve the response speed of continuous monitoring of humidified propofol gas, using ion mobility spectrometry for continuous monitoring of humidified propofol gas; The ion mobility spectrometer consists of an ion mobility tube, a heat tracing tube, a buffer tank, a flow meter (1), a vacuum pump, a flow meter (2), a drift gas, and a carrier gas; The heat tracing pipe is connected in sequence to the buffer tank, the ion migration tube, the flow meter (1), and the air pump. The ion migration tube connects the carrier gas, the drift gas and the buffer tank via a tee. The heat tracing pipe is connected to the outlet (2) and the flow meter (2) via a tee, and the flow meter (2) is connected to clean air; The carrier gas contains a dopant; In analysis mode, the flow meter (1) and the vacuum pump run continuously to extract humidified propofol gas for analysis. In cleaning mode, the flow meter (1) and the air pump keep running continuously. The flow meter (2) draws clean air, injects it for analysis, and cleans the heat tracing tube and buffer tank.

[0013] Based on the above technical solution, the outlet (2) is used to introduce humidified propofol gas in the analysis mode; The outlet (2) is used to discharge clean air in cleaning mode.

[0014] Based on the above technical solution, in the analysis mode, the humidified propofol gas, at the injection flow rate, passes through the heat tracing tube, the buffer tank, enters the ion migration tube, and is discharged through the outlet (1) to realize the analysis and detection of propofol. At this time, the flow meter (2) and clean air are not running and are not provided.

[0015] Based on the above technical solution, in the cleaning mode, a portion of the clean air passes through the heat tracing tube and buffer tank in sequence at the sample injection flow rate, enters the ion migration tube, and is discharged through the outlet (1) to quickly clean the propofol in the heat tracing tube and buffer tank; another portion of the clean air is discharged through the outlet (2), and the discharge flow rate is the difference between the cleaning flow rate and the sample injection flow rate.

[0016] Based on the above technical solution, in the analysis mode, the flow meter (1) and the pump run continuously, and their flow rate is the pumping flow rate. At this time, the injection flow rate = pumping flow rate - (drift gas flow rate + carrier gas flow rate). In cleaning mode, the flow meter (1) and the air pump keep running continuously, and the clean air is controlled to ensure that the cleaning flow rate is greater than the sample injection flow rate.

[0017] Based on the above technical solution, by switching between analysis mode, cleaning mode and analysis mode, rapid analysis of propofol and rapid cleaning of residual propofol adsorbed in the heat tracing pipe and buffer tank can be completed, shortening the response time T90 and recovery time T10.

[0018] Based on the above technical solution, the heat tracing pipe is a heatable and temperature-controlled pipe with a temperature control range of 120~170℃, a length of 2.5 meters, and the pipe material is at least one of stainless steel, passivated stainless steel, and polytetrafluoroethylene.

[0019] Based on the above technical solution, in the analysis mode, the injection flow rate of humidified propofol gas is 0.3~0.5L / min, the carrier gas flow rate is 0.1~0.2L / min, the bleaching gas flow rate is 0.4~0.6L / min, and the extraction gas flow rate is 0.8~1.1L / min; In cleaning mode, the clean air injection flow rate is 0.8~1.0L / min, and the cleaning flow rate is 0.3~0.5L / min.

[0020] Based on the above technical solution, the ion mobility spectrometry operates in positive ion mode, the dopant is anisole or toluene, the amount added is controlled by a small hole on the cap and measured by the peak intensity of the anisole ion peak, the peak intensity is between 3.0 and 5.0 V, and the relative humidity of the humidified propofol gas is 90 to 99% RH.

[0021] Beneficial effects (1) The technical solution disclosed in this invention detects humidified propofol gas and monitors the time taken from low concentration to high concentration, which is 1.6 times faster.

[0022] (2) The technical solution disclosed in this invention detects humidified propofol gas and monitors the time taken from high concentration to low concentration, which is 1.5 times faster; (3) The technical solution disclosed in this invention enables rapid cleaning of ion migration tubes and injection tubes, reduces propofol adsorption and residue, and achieves continuous monitoring and rapid response. Attached Figure Description

[0023] Figure 1 A flowchart for analyzing the pattern; Figure 2 A flowchart for the cleaning mode; Figure 3 The ion migration spectra are for propofol and the dopant anisole. Figure 4 The monitoring results of humidified propofol gas using the continuous method and the switching method in Examples 1-2 and Comparative Examples 1-2 are shown in the figure (left: high concentration - low concentration, right: low concentration - high concentration). Figure 5 The monitoring results of humidified propofol gas using the continuous method and switching method in Example 3 and Comparative Example 3 are shown (upper limit: no cleaning, high concentration - low concentration; lower limit: with cleaning, high concentration - low concentration - high concentration). Detailed Implementation

[0024] To make the objectives and technical solutions of this invention clearer, the following embodiments are provided for further explanation. However, the scope of protection of this invention is not limited to these embodiments; the embodiments are merely for illustrative purposes. Those skilled in the art should understand that any changes or equivalent substitutions that do not depart from the concept of this invention are included within the scope of protection of this invention.

[0025] Unless otherwise specified, all reagents and raw materials used in this invention are obtained through purchase.

[0026] The present invention provides a method for improving the response speed of continuous monitoring of humidified propofol gas in the specific implementation section. The analysis conditions of ion mobility spectrometry are as follows: the ion mobility spectrometry is operated in positive ion mode, the ionization source is a VUV radio frequency lamp, the ion mobility tube temperature is 120~170℃, the inner diameter of the migration region of the ion mobility tube is 20mm and the length is 7cm, the inter-ring voltage is (270~310)±10V in positive ion mode, the TP type ion gate voltage is (270~310)±10V, the gate opening time is 0.050ms, the time of each analysis cycle is 10ms, and the average number of spectra is 20.

[0027] The bleaching gas (clean air) enters from the Faraday disk end of the migration tube at a flow rate of 0.4~0.6 L / min; the carrier gas (clean air, or humidified air with water vapor added to clean air by bubbling through a series of bubble bottles, at room temperature or 37°C with humidity ≥90%RH) enters from the reaction zone of the ion migration tube at a flow rate of 0.1~0.2 L / min; the injection tube is connected to the reaction zone of the ion migration tube or connected to the reaction zone of the ion migration tube after being combined with the carrier gas through a T-connector; the vacuum pump is connected to the outlet of the ion migration tube near the radio frequency lamp, and the flow rate of the vacuum pump is adjusted to 0.8~1.1 L / min so that the injection flow rate through the injection tube is 0.3~0.5 L / min.

[0028] The dopant anisole is contained in a capped reagent bottle with a small hole punched in the cap. The reagent bottle is placed in a temperature-controlled stainless steel container (temperature controlled at 25~80℃). The stainless steel container has inlet and outlet ports connected in series with the carrier gas (clean air). Anisole is released into the carrier gas through the small hole and sent into an ion migration tube for testing and analysis. The temperature is adjusted to ensure that the peak height of anisole is between 3 and 5V when the carrier gas is clean air.

[0029] Propofol solution is contained in a capped reagent bottle with a small hole punched in the cap. The reagent bottle is placed in a constant-temperature stainless steel container (temperature controlled at 25~80℃). The stainless steel container has an air inlet and an air outlet connected in series with a carrier gas (humidified air). By controlling and changing the high and low temperatures (approximately 50℃ or approximately 37℃), high and low concentrations of humidified propofol gas can be generated for monitoring and analysis.

[0030] Ion mobility spectrometry was used to monitor propofol gas in positive ion mode, with clean air or air added as a carrier gas and anisole as a dopant.

[0031] Example 1 A method for improving the response speed of continuous monitoring of humidified propofol gas includes the following steps: Step 1: In analysis mode, the flow meter (1) and the vacuum pump are running at a vacuum flow rate of 1.0 L / min and an injection flow rate of 0.5 L / min. Humidified propofol gas (relative humidity of 90~99%RH) is introduced into the outlet (2). The humidified propofol gas passes through a 170℃ heated tube (2 mm inner diameter, 2.5 m length) and enters a 3 ml stainless steel buffer tank (200℃), and then enters the ion migration tube. At this time, drift gas (flow rate of 0.4 L / min) and carrier gas (flow rate of 0.1 L / min) are introduced and mixed with the gas to be tested in the ion migration tube. In analysis mode, the high concentration of humidified propofol gas is continuously monitored. The ion migration spectra of the humidified / unhumidified dopant anisole and the humidified / unhumidified propofol gas are shown in the figure. Figure 3 For a detailed flowchart of the analysis model, please see [link / diagram]. Figure 1 .

[0032] Step 2: While changing the concentration of humidified propofol gas (from high concentration to low concentration, specifically adjusting the concentration of humidified propofol gas from 7 ppb to 3 ppb), enter the cleaning mode; in the cleaning mode, turn on the flow meter (2) and introduce clean air to clean the propofol in the heating pipe, buffer tank and other pipelines. The peak height of propofol will quickly decrease to near the baseline. At this time, the injection flow rate of clean air is 0.5 L / min and the cleaning flow rate is 1.0 L / min. See the schematic diagram of the specific cleaning mode process. Figure 2 ; Step 3: Turn off the flow meter (2), switch to analysis mode, and continuously monitor the low concentration of humidified propofol gas. The test results are shown in [link to test results]. Figure 4 (Left image, with cleaning) The switching method takes T10+T90=4.1 minutes to monitor from high concentration to low concentration, which is 1.5 times faster than the continuous method.

[0033] Comparative Example 1 The difference from Example 1 is that it is not necessary to switch to cleaning mode; only the continuous method of analysis mode is used. The tracking graph of continuous monitoring of humidified propofol gas from high to low concentration is shown in the figure. Figure 4 (Left image, without cleaning) The time taken for continuous monitoring from high concentration to low concentration is T10 = 6.2 minutes.

[0034] Example 2 The difference from Example 1 is that a switching method was used to monitor the humidified propofol gas from low to high concentrations. Specifically, in step 1, the humidified propofol concentration was 2 ppb, and in step 2, the humidified propofol gas concentration was adjusted from 6 ppb to 2 ppb. The rest remained the same as in Example 1. The test results are shown below. Figure 4 (Right image, with cleaning) The time taken to monitor from low concentration to high concentration is T10+T90=6.4 minutes, which is 1.6 times faster than the continuous method.

[0035] Comparative Example 2 The difference from Example 2 is that it is not necessary to switch to cleaning mode; only the continuous method of analysis mode is used. The tracking graph of continuous monitoring of humidified propofol gas from low to high concentration is shown in the figure. Figure 4 (Right image, no cleaning) The time taken to monitor from low concentration to high concentration is T90 = 10.8 minutes.

[0036] Example 3 The difference from Example 1 is that in step 1, the temperature of the heat tracing pipe is 120°C, the temperature of the stainless steel buffer tank is 150°C, the evacuation flow rate is 1.1 L / min, the bleaching gas flow rate is 0.6 L / min, the carrier gas flow rate is 0.2 L / min, and the propofol injection flow rate is 0.3 L / min; in step 2, the air injection flow rate is 0.3 L / min, the purging flow rate is 0.8 L / min, and the rest is the same as in Example 1 (testing humidified propofol gas from high to low concentrations, specifically adjusting the concentration of humidified propofol gas from 5 ppb to 2 ppb, and the relative humidity of the humidified propofol gas is 90~99%RH). The test results are shown in […]. Figure 5 (Offline, cleaning has been performed) The switching method takes 6.6 minutes (T10+T90) to monitor the concentration from high to low, which is 1.2 times faster than the continuous method.

[0037] Comparative Example 3 The difference from Example 3 is that it is not necessary to switch to cleaning mode; only the continuous method of analysis mode is used. The tracking graph of continuous monitoring of humidified propofol gas from high to low concentration is shown in the figure. Figure 5 (Online, no cleaning), the time taken for continuous monitoring from high concentration to low concentration is T10=8.0 minutes.

[0038] Example 4 The difference from Example 3 is that the test involved increasing the concentration of humidified propofol gas from low to high. Specifically, the concentration of the humidified propofol gas was adjusted from 2 ppb to 5 ppb. The time taken to monitor the transition from low to high concentration using the switching method was T10 + T90 = 15.5 minutes. The switching method was 1.07 times faster than the continuous method. The test results are shown in […]. Figure 5 (Offline, cleaning process underway).

[0039] Comparative Example 4 The difference from Example 4 is that there is no need to switch to cleaning mode; only the continuous method of analysis mode is used. The continuous method takes T90 = 16.6 minutes to monitor from low concentration to high concentration.

[0040] The above description is merely a few embodiments of this application and is not intended to limit this application in any way. Although this application discloses preferred embodiments as described above, it is not intended to limit this application. Any changes or modifications made by those skilled in the art without departing from the scope of the technical solution of this application using the disclosed technical content are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. A method for improving the response speed of continuous monitoring of humidified propofol gas, characterized in that, Continuous monitoring of humidified propofol gas was performed using ion mobility spectrometry. The ion mobility spectrum consists of an ion mobility tube, a heat tracing tube, a buffer tank, a flow meter (1), a vacuum pump, a flow meter (2), a drift gas, and a carrier gas; The heat tracing pipe is connected in sequence to the buffer tank, the ion migration tube, the flow meter (1), and the air pump. The ion migration tube connects the carrier gas, the drift gas and the buffer tank via a tee. The heat tracing pipe is connected to the outlet (2) and the flow meter (2) via a tee, and the flow meter (2) is connected to clean air; The carrier gas contains a dopant; In analysis mode, the flow meter (1) and the vacuum pump run continuously to extract humidified propofol gas for analysis. In cleaning mode, the flow meter (1) and the air pump keep running continuously, the flow meter (2) draws clean air, the cleaning flow rate is controlled to be greater than the injection flow rate, the sample is injected for analysis, and the heat tracing tube and buffer tank are cleaned.

2. The response speed method according to claim 1, characterized in that, In analysis mode, the outlet (2) is used to introduce humidified propofol gas; The outlet (2) is used to discharge clean air in cleaning mode.

3. The response speed method according to claim 1, characterized in that, In the analysis mode, the humidified propofol gas is introduced at the sample flow rate, passing through the heat tracing tube, the buffer tank, the ion migration tube, and then discharged through the outlet (1) to achieve the analysis and detection of propofol. At this time, the flow meter (2) and the clean air are not running.

4. The response speed method according to claim 1, characterized in that, In the cleaning mode, a portion of the clean air passes through the heat tracing tube and buffer tank at the injection flow rate, enters the ion migration tube, and is discharged through the outlet (1) to quickly clean the propofol in the heat tracing tube and buffer tank; another portion of the clean air is discharged through the outlet (2), and the discharge flow rate is the difference between the cleaning flow rate and the injection flow rate.

5. The response speed method according to claim 1, characterized in that, By switching between analysis mode, cleaning mode, and analysis mode, rapid analysis of propofol and rapid cleaning of residual propofol adsorbed in the heat tracing pipe and buffer tank can be completed, shortening the response time T90 and recovery time T10.

6. The response speed method according to claim 1, characterized in that, The heat tracing pipe is a heatable and temperature-controlled pipeline with a temperature control range of 120~170℃, a length of 2.5 meters, and the pipeline material is at least one of stainless steel, passivated stainless steel, and polytetrafluoroethylene.

7. The response speed method according to claim 1, characterized in that, In analysis mode, the injection flow rate of humidified propofol gas is 0.3~0.5 L / min, the carrier gas flow rate is 0.1~0.2 L / min, the bleaching gas flow rate is 0.4~0.6 L / min, and the extraction gas flow rate is 0.8~1.1 L / min; In cleaning mode, the clean air injection flow rate is 0.8~1.0L / min, and the cleaning flow rate is 0.3~0.5L / min.

8. The response speed method according to claim 1, characterized in that, The ion mobility spectrometry is operated in positive ion mode, and the dopant is anisole or toluene. The amount added is controlled by a small hole on the cap and is measured by the peak intensity of the anisole ion peak, which is between 3.0 and 5.0 V. The relative humidity of the humidified propofol gas is 90 to 99% RH.

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