A processing device and analysis method for extraction liquid for ultrasonic extraction

Abstract

The invention relates to the technical field of extraction detection, and in particular to a processing device and an analysis method for extraction liquid for ultrasonic extraction, comprising a support, a liquid inlet pipe, a mixing barrel, a lead-out pipe, a separation barrel, a liquid outlet pipe, a processing table, a mixing mechanism and a separation mechanism; the bottom end of the support is the processing table, the side wall of the mixing barrel is provided with a liquid inlet pipe, and the side wall of the mixing barrel opposite to the liquid inlet pipe is provided with a lead-out pipe; the separation barrel is provided on the support, the separation barrel is connected with the mixing barrel through the lead-out pipe, and the liquid outlet pipe is provided at the lower end of the separation barrel; the mixing mechanism is provided in the mixing barrel; the separation mechanism is provided in the separation barrel; the invention drives the rotation of the stirring blade of the motor of the mixing mechanism to stir and mix the drug sample fed into the feeding port, the design of the one-way plate ensures that ethanol can evenly overflow and be fully mixed with the drug sample to be tested, thereby improving the extraction efficiency of the target component, and the slope provided at the connection between the stirring chamber and the transition chamber is combined to ensure the uniformity of mixing.

Description

Technical Field

[0001] The invention relates to the technical field of extraction detection, and in particular to a processing device and an analysis method for extraction liquid used for ultrasonic extraction. Background Art

[0002] In the field of drug testing, especially for the rapid screening of illegally added antihypertensive drugs in traditional Chinese medicines and edible products, existing technical means mainly rely on efficient extraction and analysis methods, among which ultrasonic extraction combined with magnetic solid phase extraction (MSPE) and two-dimensional ultra-high performance liquid chromatography-tandem mass spectrometry (2D-UPLC-MS / MS) technology has become a commonly used method.

[0003] Ultrasonic extraction uses ultrasonic energy to make the target components in the sample fully contact with the extraction solvent, thereby efficiently extracting the target components. It has the advantages of high extraction efficiency, simple operation and the ability to process a variety of samples. Magnetic solid phase extraction uses magnetic adsorbents (such as Fe3O4@MIL-100(Fe)) to selectively adsorb the target components and separate the adsorbed target components from the sample by magnetic separation. It has the advantages of simple operation, high selectivity and easy automation. Two-dimensional ultra-high performance liquid chromatography-tandem mass spectrometry (2D-UPLC-MS / MS) combines two-dimensional chromatographic separation and mass spectrometry detection technology to achieve high-sensitivity and high-resolution detection of multiple target components in complex samples, and can provide accurate qualitative and quantitative analysis results.

[0004] However, during the sample processing stage, the drug sample needs to be fully mixed with the extraction solvent to ensure efficient extraction of the target component. However, due to limitations in manual operation or equipment design, the mixing process is prone to unevenness, resulting in reduced extraction efficiency of the target component, thereby affecting the accuracy of subsequent test results. At the same time, the amount of extraction solvent added is an important factor affecting the extraction efficiency and test results. Existing technical means usually rely on manual addition of extraction solvents or use simple automated equipment for quantitative addition. However, due to equipment accuracy limitations or operator errors, the actual amount of extraction solvent added is difficult to accurately control. This error not only affects the extraction efficiency of the target component, but may also lead to co-extraction of impurities in the sample, thereby interfering with subsequent analysis. Summary of the invention

[0005] The technical problem to be solved by the present invention is that during the sample processing stage, due to limitations in manual operation or equipment design, large errors are prone to occur in the drug mixing process and the extraction solvent addition process, resulting in reduced extraction efficiency of the target component, thereby affecting the accuracy of subsequent test results.

[0006] In order to solve the technical problem, the technical solution adopted by the present invention is:

[0007] In a first aspect, a processing device for extraction liquid for ultrasonic extraction is provided, comprising a bracket, a liquid inlet pipe, a mixing barrel, a lead-out pipe, a separation barrel, a liquid outlet pipe, a processing table, a mixing mechanism and a separation mechanism; the bottom end of the bracket is the processing table, the mixing barrel is mounted on the bracket, the side wall of the mixing barrel is mounted with a liquid inlet pipe, and the side wall of the mixing barrel opposite to the liquid inlet pipe is mounted with a lead-out pipe; the separation barrel is mounted on the bracket, the separation barrel is connected to the mixing barrel through the lead-out pipe, and the liquid outlet pipe is mounted at the lower end of the separation barrel; the mixing mechanism is mounted in the mixing barrel, the mixing mechanism stirs the drug sample to be tested by rotating the stirring blade, and at the same time mixes the drug sample to be tested with ethanol overflowing through the one-way plate; the separation mechanism is mounted in the separation barrel, the separation mechanism separates the drug sample to be tested by ultrasonic waves, and further separates the drug sample to be tested in combination with the guide plate.

[0008] Optionally, the mixing mechanism includes a stirring assembly, a feeding port, a stirring chamber, a transition chamber, an extension rod and a one-way plate; the stirring chamber is installed at the upper end of the transition chamber, the stirring assembly and the stirring chamber are installed coaxially, the feeding port is arranged on one side of the stirring chamber, the transition chamber is installed coaxially with the stirring chamber and is arranged at the lower end of the stirring chamber; one end of the extension rod is rotatably connected to the one-way plate coaxially, and the one-way plate is rotatably connected in the transition chamber.

[0009] Optionally, the stirring assembly includes a motor, a partition and a stirring blade; the motor is installed at the upper end of the stirring barrel and the output shaft of the motor is connected to the extension rod, wherein a locking piece is provided between the extension rod and the output shaft of the motor; the partition is installed coaxially with the motor output, and the stirring blade is installed on the lower bottom surface of the partition.

[0010] Optionally, a plurality of precipitation holes are provided on the surface of the one-way plate, a through hole is provided at the axis of the one-way plate, a spiral pattern is provided in the through hole, and the spiral pattern is in contact with the surface of the extension rod; a limit block is provided on the side wall of the one-way plate.

[0011] Optionally, the allowed flow direction of the water in the precipitation hole is unidirectional and vertically upward.

[0012] Optionally, the plane at the connection between the stirring chamber and the transition chamber is provided with a slope and the angle between the plane and the slope is an acute angle.

[0013] Optionally, the separation mechanism includes an ultrasonic generating tube, an inner tube, a filter membrane and a guide plate; the ultrasonic generating tube surrounds the inner tube in a circular array, and the inner tube is installed in a separation barrel and coaxially; the filter is arranged on the outer surface of the inner tube, and the guide plate is arranged in a sheet shape and on the side wall of the inner tube, wherein the guide plate is an electromagnet.

[0014] Optionally, filter holes are provided on the inner surface of the inner tube and intervals are provided between adjacent plates.

[0015] Optionally, the lower end of the guide plate is rotatably connected to the bottom end of the inner tube, and a blind hole is provided on the surface of the guide plate.

[0016] In a second aspect, a method for analyzing an extraction liquid for ultrasonic extraction is provided, the method using the processing device of the first aspect, comprising the following steps:

[0017] S1: Weigh a certain amount of the drug sample to be tested by an electronic balance, and then put the drug sample into the stirring chamber through the feeding port;

[0018] S2: Then the motor is turned on, a certain volume of methanol is added to the mixing barrel through the liquid inlet pipe, and ethanol is sent to mix with the drug sample to be tested through the one-way plate;

[0019] S3: ultrasonic extraction is performed on the liquid in the inner tube through an ultrasonic generating tube, and the temperature is cooled to room temperature after ultrasonic extraction for 30 minutes;

[0020] S4: After the extraction is completed, an additional motor is installed at the upper end of the separation barrel, and then the extract is centrifugally filtered through the inner tube and the filter membrane to remove solid impurities in the sample and obtain a clarified extract;

[0021] S5: adding an appropriate amount of Fe3O4@MIL-100(Fe) magnetic adsorbent to the filtered extract through a guide plate; mixing the extract with the adsorbent, and stirring by rotating the inner tube with a motor to ensure full contact, and the stirring time is 10 minutes;

[0022] S6: The guide plate is electrified, and the magnetic adsorbent containing the target antihypertensive drug is separated from the solution by magnetism; then, an appropriate amount of elution solvent is added to the separated magnetic adsorbent, and the elution time is 5 to 15 minutes to ensure that the target substance is completely eluted;

[0023] S7: Finally, the guide plate and the inner tube are separated, and the eluate is sent out through the liquid outlet tube, and then the eluate is injected into the 2D-UPLC-MS / MS system for analysis.

[0024] The beneficial effects of the present invention are as follows:

[0025] 1. The present invention drives the stirring blade to rotate by the motor of the mixing mechanism to stir and mix the drug sample put into the feeding port. At the same time, the design of the one-way plate ensures that ethanol can overflow evenly and fully mix with the drug sample to be tested, thereby improving the extraction efficiency of the target component. Combined with the slope set at the connection between the stirring chamber and the transition chamber, it is helpful to evenly distribute the solvent and ensure the uniformity of mixing.

[0026] 2. The present invention realizes precise control of the amount of extraction solvent added by setting the liquid inlet pipe and the outlet pipe, avoiding the addition error caused by manual operation or equipment precision limitation. The separation mechanism uses ultrasonic energy to separate the drug sample to be tested through the design of the ultrasonic generating tube and the inner tube, and combines the function of the filter membrane and the guide plate to realize efficient filtration and separation of the extract.

[0027] 3. The present invention provides a raised slope between the transition chamber and the stirring chamber, thereby ensuring that the overflowed methanol can enter the stirring chamber and the stirring area of ​​the stirring blades under the action of gravity, while ensuring the stirring efficiency and the lubrication efficiency of the methanol. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0029] The above and other aspects of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0030] Figure 1 It is an overall schematic diagram of the present invention;

[0031] Figure 2 It is a cross-sectional perspective schematic diagram of a mixing barrel of the present invention;

[0032] Figure 3 is a cross-sectional view of the stirring mechanism of the present invention;

[0033] Figure 4 It is a schematic diagram of the internal structure of the stirring chamber of the present invention;

[0034] Figure 5 It is a cross-sectional perspective schematic diagram of the separation barrel of the present invention;

[0035] Figure 6 It is a schematic cross-sectional view of a separation barrel of the present invention;

[0036] Figure 7 It is a structural diagram of a one-way plate of the present invention;

[0037] Figure 8 is the multiple reaction monitoring chromatogram of indapamide of the present invention;

[0038] Fig. 9 is a multi-reaction monitoring chromatogram of timolol of the present invention;

[0039] Fig.10 is a multiple reaction monitoring chromatogram of telmisartan of the present invention;

[0040] Fig.11 is a labetalol reaction monitoring chromatogram of the present invention;

[0041] Fig.12 It is the multiple reaction monitoring chromatogram of propranolol of the present invention;

[0042] Fig.13 It is the multiple reaction monitoring chromatogram of irbesartan of the present invention;

[0043] In the figure: 1. bracket; 2. liquid inlet pipe; 3. mixing barrel; 4. outlet pipe; 5. separation barrel; 6. liquid outlet pipe; 7. processing table; 8. mixing mechanism; 81. stirring assembly; 811. motor; 812. partition; 813. stirring blade; 82. stirring chamber; 821. feeding port; 83. transition chamber; 84. extension rod; 85. one-way plate; 851. precipitation hole; 852. through hole; 853. spiral pattern; 854. limit block; 9. separation mechanism; 91. ultrasonic generating tube; 92. inner tube; 921. filter hole; 922. interval; 93. filter membrane; 94. guide plate; 941. blind hole. DETAILED DESCRIPTION

[0044] In order to better understand the above technical solution, the above technical solution will be described in detail below in conjunction with the accompanying drawings and specific implementation methods.

[0045] Embodiment 1:

[0046] like Figures 1 to 6 As shown, a processing device for extracting liquid for ultrasonic extraction comprises a support 1, a liquid inlet pipe 2, a mixing barrel 3, a lead-out pipe 4, a separation barrel 5, a liquid outlet pipe 6, a processing table 7, a mixing mechanism 8 and a separation mechanism 9; the bottom end of the support 1 is the processing table 7, the mixing barrel 3 is mounted on the support 1, the side wall of the mixing barrel 3 is mounted with a liquid inlet pipe 2, and the side wall of the mixing barrel 3 opposite to the liquid inlet pipe 2 is mounted with a lead-out pipe 4; the separation barrel 5 is mounted on the support 1, the separation barrel 5 is connected with the mixing barrel 3 through the lead-out pipe 4, and the liquid outlet pipe 6 is mounted at the lower end of the separation barrel 5; the mixing mechanism 8 is mounted in the mixing barrel 3, the mixing mechanism 8 stirs the drug sample to be tested by rotating the stirring blade, and at the same time mixes the drug sample to be tested with ethanol overflowing through the one-way plate 85; the separation mechanism 9 is mounted in the separation barrel 5, the separation mechanism 9 separates the drug sample to be tested by ultrasonic wave, and further separates the drug sample to be tested in combination with the guide plate 94.

[0047] like Figure 1As shown, the mixing mechanism 8 includes a stirring assembly 81, a feeding port 821, a stirring chamber 82, a transition chamber 83, an extension rod 84 and a one-way plate 85; the stirring chamber 82 is installed at the upper end of the transition chamber 83, the stirring assembly 81 and the stirring chamber 82 are installed coaxially, the feeding port 821 is arranged on one side of the stirring chamber 82, the transition chamber 83 is installed coaxially with the stirring chamber 82 and is arranged at the lower end of the stirring chamber 82; one end of the extension rod 84 is rotatably connected to the one-way plate 85 coaxially, and the one-way plate 85 is rotatably connected in the transition chamber 83; the mixing barrel 3 and the separation barrel 5 are both arranged to be placed vertically, wherein the horizontal height of the upper surface of the mixing barrel 3 is arranged to be lower than the outlet pipe 4, so that the stirred and mixed solvent can enter the separation barrel 5 through the outlet pipe 4.

[0048] Another point worth mentioning is that the feeding port 821 is arranged on the upper surface of the stirring chamber 82 and can be detachably opened and closed, so that a variety of medicinal materials to be tested can be put into the stirring chamber 82 before stirring; methanol can be introduced into the liquid inlet pipe 2, and after the methanol is added, it first fills the inside of the transition chamber 83, and then with the continuous input, the liquid level gradually rises, and then under the action of the one-way plate 85, part of the liquid can be input into the stirring chamber 82.

[0049] like Figure 4 As shown, the stirring assembly 81 includes a motor 811, a partition 812 and a stirring blade 813; the motor 811 is installed at the upper end of the stirring barrel and the output shaft of the motor 811 is connected to the extension rod 84, wherein a locking piece is provided between the extension rod 84 and the output shaft of the motor 811; the partition 812 is installed coaxially with the output of the motor 811, and the stirring blade 813 is installed on the lower bottom surface of the partition 812; the locking piece can lock the extension rod 84 as needed, and then can drive the extension rod 84 to rotate in a locked state together with the output shaft of the motor 811.

[0050] like Figure 2 and Figure 7As shown, the one-way plate 85 is provided with a plurality of precipitation holes 851 on its surface, and the permitted flow direction of the water in the precipitation holes 851 is one-way and vertically upward; a through hole 852 is provided at the axis of the one-way plate 85, and a spiral pattern 853 is provided in the through hole 852, and the spiral pattern 853 is in contact with the surface of the extension rod 84; a limit block 854 is provided on the side wall of the one-way plate, and while the limit block 854 is provided, a groove for accommodating the limit block 854 is provided on the inner wall of the transition cavity 83, and the groove is arranged vertically, thereby ensuring the vertical movement of the one-way plate 85; the through hole 852 is used to contact with the extension rod 84 The one-way plate 85 can fit together, and then the one-way plate 85 can rotate along the spiral pattern 853 under the action of the through hole 852, and then can compress the current solvent level, and then precipitate the solvent through the one-way precipitation hole 851 of the one-way plate 85, and then merge with the medicinal materials to be tested in the stirring chamber 82; the limit block 854 is used to fix the one-way plate 85 in the transition chamber 83 to prevent it from being unable to rotate and rise through the spiral pattern 853 when the extension rod 84 rotates. The limitation of the limit block 854 can ensure that the one-way plate 85 can be raised or lowered along the rotation of the extension rod 84 in a locked state.

[0051] like Figure 3 As shown, the plane at the connection between the stirring chamber 82 and the transition chamber 83 is provided with a slope and the angle between the plane and the slope is an acute angle; by raising the plane, it can be ensured that after the solvent is precipitated into the stirring chamber 82 by the one-way plate 85, the inclined slope can be used to introduce the solvent into both sides of the stirring chamber 82, and then the stirring blade 813 can be used to merge the solvent with the drug to be tested; at the same time, in order to match the slope setting, the stirring blade 813 is set to fit the stirring chamber 82 on both sides, and a notch is set at the position fitting the slope, that is, the stirring blade is an irregular shape.

[0052] The separation mechanism 9 includes an ultrasonic generating tube 91, an inner tube 92, a filter membrane 93 and a guide plate 94; the ultrasonic generating tube 91 is arranged in a circular array around the inner tube 92, and the inner tube 92 is installed in the separation barrel 5 and is installed coaxially; the filter membrane 93 is arranged on the outer surface of the inner tube 92, and the guide plate 94 is arranged in a sheet shape and is arranged on the side wall of the inner tube 92, wherein the guide plate 94 is an electromagnet; the ultrasonic generating tube 91 uniformly surrounds the inner tube 92, thereby being able to uniformly perform ultrasonic extraction on the solution to be tested.

[0053] like Figure 6 As shown, the inner surface of the inner tube 92 is provided with filter holes 921 and intervals 922 are provided between adjacent plates; the filter holes 921 are provided, and after the ultrasonic wave ends, a motor can be connected to the upper end of the inner tube 92 to rotate the inner tube 92, so that the solvent in the inner tube 92 is centrifuged out of the inner tube 92, and in this process, part of the substance will be filtered through the filter membrane 93.

[0054] like Figure 5 As shown, the lower end of the guide plate 94 is rotatably connected to the bottom end of the inner tube 92, and a blind hole 941 is provided on the surface of the guide plate 94; the lower end of the guide plate 94 is set at an inclined angle, so that materials can be added through the upper end of the guide plate 94, and then flow down along the inner wall of the guide plate 94; the guide plate 94 and the inner tube 92 are rotatably connected, so that when the motor drives the inner tube 92 to rotate, the guide plate 94 can keep the inner tube 92 from rotating. Maintain the original state, and then be able to fit the inner tube 92. In order to ensure that the final liquid can be discharged from the inner tube 92, an overflow hole that can be opened and closed is set between the guide plate 94 and the inner tube 92. The overflow hole can be opened and closed by the central control adjustment, and then the overflow hole is opened to discharge the final liquid through the liquid outlet pipe 6; under the setting of the blind hole 941, the distance where part of the drug solution stays can be increased, and finally merged with the remaining solvent; finally, the solvent is removed from the workbench and sent to the 2D-UPLC-MS / MS system for analysis.

[0055] Embodiment 2:

[0056] This method is applicable to the determination of six antihypertensive chemical drugs, including indapamide, timolol, telmisartan, labetalol, propranolol and irbesartan, in traditional Chinese medicines and antihypertensive products with medicinal and edible properties.

[0057] Prepare standard stock solution (100 μg / mL) as required. First, accurately weigh 10.0 mg of indapamide, timolol, telmisartan, labetalol, propranolol, and irbesartan standards (3.5), respectively, and place them in 100 mL brown volumetric flasks. Dissolve and dilute to the scale with methanol, shake well, and prepare standard stock solutions with a concentration of 100 μg / mL. Store at -18°C in the dark.

[0058] Then mix the standard intermediate working solution, accurately pipette 0.15 mL, 1.0 mL, 0.1 mL, 0.625 mL, 0.1 mL, and 0.05 mL of indapamide, timolol, telmisartan, labetalol, propranolol, and irbesartan stock solutions (100 μg / mL) (3.6.1), respectively, place them in a 50 mL brown volumetric flask, dilute to the mark with methanol, shake well, and prepare the mixed standard intermediate working solution. Store at -18℃ away from light.

[0059] Then prepare a series of matrix standard working solutions. Pipette 0.01 mL, 0.1 mL, 0.2 mL, 0.4 mL, 0.8 mL, and 1.6 mL of the mixed standard intermediate working solution (3.6.2) into a 10 mL volumetric flask, dilute to the mark with the blank matrix extract (5.1.3), and shake well. These are the series of mixed standard working solutions. The concentrations of indapamide are 0.3 μg / L, 3 μg / L, 6 μg / L, 12 μg / L, 24 μg / L, and 48 μg / L, respectively; the concentrations of timolol are 2 μg / L, 20 μg / L, 40 μg / L, 80 μg / L, 160 μg / L, and 320 μg / L, respectively; the concentrations of propranolol and telmisartan are 0.2 μg / L, 2 μg / L, 4 μg / L, 8 μg / L, 16 μg / L, and 32 The concentrations of labetalol are 1.25 μg / L, 12.5 μg / L, 25 μg / L, 50 μg / L, 100 μg / L, and 200 μg / L, and the concentrations of irbesartan are 0.1 μg / L, 1 μg / L, 2 μg / L, 4 μg / L, 8 μg / L, and 16 μg / L. Prepare a fresh mixed standard working solution before use or prepare it at an appropriate concentration according to the instrument response.

[0060] The equipment required for this method includes: high performance liquid chromatography-tandem mass spectrometer equipped with an electrospray ionization (ESI) source, microporous filter membrane: 0.22 µm, organic phase type, electronic balance: sensitivity of 0.00001 g and 0.0001 g respectively, and ultrasonic cleaner.

[0061] A certain amount of the drug sample to be tested is weighed by an electronic balance, and then the drug sample is put into the stirring chamber 82 through the feeding port 821.

[0062] Then, the motor 811 is turned on, a certain volume of methanol is added to the mixing barrel 3 through the liquid inlet pipe 2, and the ethanol is sent to mix with the drug sample to be tested through the one-way plate 85;

[0063] The liquid in the inner tube 92 is ultrasonically extracted by the ultrasonic generating tube 91, and the temperature is cooled to room temperature after ultrasonic extraction for 30 minutes;

[0064] After the extraction is completed, an additional motor is installed at the upper end of the separation barrel 5, and then the extract is centrifugally filtered through the inner tube 92 and the filter membrane 93 to remove solid impurities in the sample and obtain a clarified extract;

[0065] Add an appropriate amount of Fe3O4@MIL-100 (Fe) magnetic adsorbent to the filtered extract through the guide plate 94; mix the extract and the adsorbent, and stir by rotating the inner tube 92 by the motor to ensure full contact, and the stirring time is 10 minutes;

[0066] The guide plate 94 is energized to separate the magnetic adsorbent containing the target antihypertensive drug from the solution by magnetism; then, a proper amount of elution solvent is added to the separated magnetic adsorbent, and the elution time is 5 to 15 minutes to ensure that the target substance is completely eluted;

[0067] Finally, the guide plate 94 and the inner tube 92 are separated, and the eluent is sent out through the liquid outlet pipe 6, and then the eluent is injected into the 2D-UPLC-MS / MS system for analysis.

[0068] Chromatographic column: C18 column (2.1×50 mm, 2.7 µm).

[0069] Mobile phase: A is 0.1% formic acid aqueous solution (3.4), B is acetonitrile solution (3.1), and the reference gradient elution program is shown in Table 1.

[0070] Flow rate: 300 μL / min.

[0071] Column temperature: 35 ℃.

[0072] Injection volume: 1 μL.

[0073] Table 1 Reference gradient elution program

[0074] Gradient time / min Mobile phase A (%) Mobile phase B (%) 0.00 90 10 1.00 90 10 8.00 10 90 8.50 90 10 12 90 10

[0075] Note: When there are co-eluting components that affect the detection of target compounds, the mobile phase ratio can be appropriately adjusted to separate the interfering components as much as possible to reduce interference.

[0076] Mass spectrometry conditions:

[0077] Ion source: electrospray ion source (ESI source).

[0078] Detection method: multiple reaction monitoring (MRM).

[0079] Scanning mode: positive ion mode.

[0080] Curtain gas (CUR), nebulizer gas (GS1), auxiliary gas (GS2), and collision gas (CAD) are all high-purity nitrogen or other suitable gases. The corresponding parameters should be adjusted before use to make the mass spectrometer sensitivity meet the detection requirements. Parameters such as electrospray voltage (IS), declustering voltage (DP), and collision energy (CE) should be optimized to the best sensitivity before use. Information such as monitoring ion pairs and quantitative ion pairs is shown in Table 2.

[0081] Table 2 Maximum allowable deviation of relative ion abundance for qualitative confirmation

[0082]

[0083] Then, the matrix standard series working solutions are measured according to the instrument reference conditions, i.e., the chromatographic conditions and the mass spectrometry conditions, to obtain the chromatographic peak areas of the corresponding standard solutions. The standard curve is drawn with the concentration of the matrix standard series working solutions as the abscissa and the peak area of ​​the chromatographic peak as the ordinate.

[0084] Among them, the sample and standard working solution are measured according to the conditions of high performance liquid chromatography-tandem mass spectrometry, and the chromatographic retention time of each compound in the sample and the standard solution is recorded. When a chromatographic peak with the same retention time as a certain standard mass chromatographic peak is detected in the sample (the variation range is within ±2.5%), and the deviation between the relative abundance ratio of the monitoring ion pair selected in the sample chromatogram and the relative abundance ratio of the ion of the standard solution of equivalent concentration does not exceed the range specified in Table 1, it can be determined that the corresponding compound is detected in the sample.

[0085] The sample solution is measured according to the instrument reference conditions to obtain the corresponding chromatographic peak area of ​​the sample solution; the concentration of the component in the test solution is obtained according to the standard curve, and the number of parallel measurements is not less than two times.

[0086] See the standard chromatogram for Figure 8-Figure 13 .

[0087] Substitute the concentration measured by liquid chromatography-mass spectrometry into the following formula to calculate the content:

[0088] ;

[0089] Where:

[0090] X — the content of each analyte in the sample, in milligrams per kilogram (mg / kg);

[0091] c — the concentration of each analyte in the test solution read from the standard curve, in micrograms per liter (μg / L);

[0092] V — Final volume of sample solution, in milliliters (mL);

[0093] m — the mass represented by the sample solution, in grams (g);

[0094] K— dilution factor.

[0095] The calculation result is expressed as the arithmetic mean of two independent determination results obtained under repeatability conditions, and the result is rounded to three significant figures.

[0096] It should be mentioned that when the sample weight was 1 g and the fixed volume was 50 mL, the detection limits of indapamide, timolol, telmisartan, labetalol, propranolol and irbesartan in this method were 0.002 mg / kg, 0.004 mg / kg, 0.003 mg / kg, 0.02 mg / kg, 0.003 mg / kg and 0.002 mg / kg, respectively, and the quantification limits were 0.016 mg / kg, 0.027 mg / kg, 0.01 mg / kg, 0.058 mg / kg, 0.0095 mg / kg and 0.007 mg / kg, respectively.

[0097] The description herein is provided to enable one of ordinary skill in the art to implement or use the present disclosure. Various modifications to the present disclosure will be apparent to one of ordinary skill in the art, and the general principles defined herein may be applied to other variations without departing from the scope of the present disclosure. Therefore, the present disclosure is not limited to the examples and designs described herein, but should be given the broadest scope consistent with the principles and novel features disclosed herein.

Claims

1. A processing device for extracting liquid for ultrasonic extraction, comprising a support (1), a liquid inlet pipe (2), a mixing barrel (3), a lead-out pipe (4), a separation barrel (5), a liquid outlet pipe (6) and a processing table (7); the bottom end of the support (1) is the processing table (7), the mixing barrel (3) is mounted on the support (1), the side wall of the mixing barrel (3) is mounted with a liquid inlet pipe (2), and the side wall of the mixing barrel (3) opposite to the liquid inlet pipe (2) is mounted with a lead-out pipe (4); the separation barrel (5) is mounted on the support (1), the separation barrel (5) is connected with the mixing barrel (3) through the lead-out pipe (4), and the liquid outlet pipe (6) is mounted at the lower end of the separation barrel (5); characterized in that: It also includes a mixing mechanism (8) and a separation mechanism (9); the mixing mechanism (8) is installed in the mixing barrel (3), and the mixing mechanism (8) stirs the administered drug sample by rotating the stirring blades, and at the same time, the ethanol overflows through the one-way plate (85) to mix the drug sample; the separation mechanism (9) is installed in the separation barrel (5), and the separation mechanism (9) separates the drug sample by ultrasonic waves, and further separates the drug sample in combination with the guide plate (94); The mixing mechanism (8) comprises a stirring assembly (81), a feeding port (821), a stirring chamber (82), a transition chamber (83), an extension rod (84) and a one-way plate (85); the stirring chamber (82) is mounted at the upper end of the transition chamber (83); the stirring assembly (81) and the stirring chamber (82) are coaxially mounted; the feeding port (821) is arranged at one side of the stirring chamber (82); the transition chamber (83) is coaxially mounted with the stirring chamber (82) and is arranged at the lower end of the stirring chamber (82); one end of the extension rod (84) is coaxially rotatably connected to the one-way plate (85); and the one-way plate (85) is rotatably connected in the transition chamber (83); The stirring assembly (81) comprises a motor (811), a partition (812) and a stirring blade (813); the motor (811) is mounted on the upper end of the stirring barrel, and the output shaft of the motor (811) is connected to the extension rod (84), wherein a locking piece is provided between the extension rod (84) and the output shaft of the motor (811); the partition (812) is mounted coaxially with the output shaft of the motor (811), and the stirring blade (813) is mounted on the lower bottom surface of the partition (812); The one-way plate (85) is provided with a plurality of precipitation holes (851) on its surface, a through hole (852) is provided at the axis of the one-way plate (85), a spiral pattern (853) is provided in the through hole (852), and the spiral pattern (853) is in contact with the surface of the extension rod (84); a limit block (854) is provided on the side wall of the one-way plate; The permitted flow direction of the water in the precipitation hole (851) is unidirectional and vertically upward; The plane at the connection between the stirring chamber (82) and the transition chamber (83) is provided with a slope, and the angle between the plane and the slope is an acute angle.

2. The ultrasonic extraction liquid processing device according to claim 1, characterized in that: The separation mechanism (9) comprises an ultrasonic generating tube (91), an inner tube (92), a filter membrane (93) and a guide plate (94); the ultrasonic generating tube (91) is arranged in a ring array around the inner tube (92), and the inner tube (92) is installed in the separation barrel (5) and is installed coaxially; the filter membrane (93) is arranged on the outer surface of the inner tube (92), and the guide plate (94) is arranged in a sheet shape and is arranged on the side wall of the inner tube (92), wherein the guide plate (94) is an electromagnet.

3. The ultrasonic extraction liquid processing device according to claim 2, characterized in that: The inner surface of the inner tube (92) is provided with filter holes (921), and intervals (922) are provided between adjacent plates.

4. The ultrasonic extraction liquid treatment device according to claim 2, characterized in that: The lower end of the guide plate (94) is rotatably connected to the bottom end of the inner tube (92), and a blind hole (941) is provided on the surface of the guide plate (94).

5. A method for analyzing an extraction liquid for ultrasonic extraction, the method using an extraction liquid processing device for ultrasonic extraction according to any one of claims 2 to 4, characterized in that: The analysis method of the extraction liquid for ultrasonic extraction comprises the following steps: S1: Weigh a certain amount of the drug sample to be tested using an electronic balance, and then feed the drug sample into the stirring chamber (82) through the feeding port (821); S2: Then, the motor (811) is turned on, a certain volume of methanol is added to the mixing barrel (3) through the liquid inlet pipe (2), and ethanol is sent to mix with the drug sample to be tested through the one-way plate (85); S3: ultrasonic extraction is performed on the liquid in the inner tube (92) through the ultrasonic generating tube (91), and the liquid is then cooled to room temperature after ultrasonic extraction for 30 minutes; S4: After the extraction is completed, an additional motor is installed at the upper end of the separation barrel (5), and the extract is centrifugally filtered through the inner tube (92) and the filter membrane (93) to remove solid impurities in the sample and obtain a clarified extract; S5: adding an appropriate amount of Fe3O4@MIL-100(Fe) magnetic adsorbent to the filtered extract through the guide plate (94); mixing the extract and the adsorbent, and stirring by rotating the inner tube (92) by a motor to ensure full contact, and the stirring time is 10 minutes; S6: energizing the guide plate (94) to separate the magnetic adsorbent containing the target antihypertensive drug from the solution by magnetism; then adding an appropriate amount of elution solvent to the separated magnetic adsorbent, and the elution time is 5 to 15 minutes to ensure that the target substance is completely eluted; S7: Finally, the guide plate (94) and the inner tube (92) are separated, and the eluate is sent out through the liquid outlet tube (6), and then the eluate is injected into the 2D-UPLC-MS / MS system for analysis.

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