A method for detecting surface residual drugs by atmospheric open ion source tandem mass spectrometry

Abstract

The application discloses a method for detecting surface residual drugs by atmospheric open ion source tandem mass spectrometry, comprising the following steps: collecting the surface residual substances by using the wetted adsorption material to obtain sample adsorption material; placing the sample adsorption material in the excitation area of the atmospheric open ion source, ionizing the residual substances by using the first atmospheric open ion source, introducing the ionized residual substances into the tandem mass spectrometer for analysis, and outputting the first mass spectrum data; switching to the second atmospheric open ion source according to the charge ratio characteristics of the first mass spectrum data to ionize the residual substances, introducing the ionized residual substances into the tandem mass spectrometer for analysis, and outputting the second mass spectrum data; and matching the second mass spectrum data to output the detection result corresponding to the mass spectrum data. The method can ensure the accuracy of the detection result by preliminary detection through the first atmospheric open ion source, and then targetedly using the second atmospheric open ion source suitable for the preliminary detection result for result verification.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of detection analysis, and in particular to a method for detecting surface residual drugs by atmospheric open ion source tandem mass spectrometry. BACKGROUND

[0002] Drug abuse has become a global social problem, posing a serious threat to public safety and health. In the current drug suppression work, rapid and accurate on-site detection technology is the key link to block the spread of drugs. Traditional drug detection methods such as chromatography-mass spectrometry have high accuracy, but have limitations such as expensive equipment, long analysis period (usually several hours) and the need for professional operation, making it difficult to meet the needs of on-site drug screening.

[0003] Current on-site drug screening methods usually use drug detection kits based on immunization. The technical route of the kit mainly includes colloidal gold method and fluorescence method. The colloidal gold method is relatively stable and has been widely used in urine tests and saliva tests for drug users, but it has the disadvantage of poor sensitivity and cannot be used for trace sample detection such as residual drugs on site. It also has certain cross-reaction and false positive problems. The fluorescence method has high sensitivity and can be used for trace sample detection such as residual drugs on site, but it is relatively complex to operate and requires the support of various auxiliary equipment (such as incubators, timers, and fluorescence detection instruments). Compared with the colloidal gold method, it is easily disturbed by the matrix of the test material and is prone to false positives, making it difficult to accurately determine the true situation of drug residues on site. SUMMARY

[0004] The present application provides a method for detecting surface residual drugs by atmospheric open ion source tandem mass spectrometry to solve the technical problem of low detection accuracy in current on-site drug detection methods.

[0005] To solve the above technical problems, in a first aspect, the present application provides a method for detecting surface residual drugs by atmospheric open ion source tandem mass spectrometry, comprising:

[0006] The organic solvent is used to wet the adsorbent material, and then the wet adsorbent material is used to wipe the surface of the object to collect the residual material on the surface of the object, obtaining a sample adsorbent material;

[0007] The sample adsorbent material is placed in the excitation region of the atmospheric open ion source, and a first atmospheric open ion source is used to ionize the residual material on the sample adsorbent material, and the ionized residual material is introduced into a tandem mass spectrometer for analysis, outputting first mass spectrometry data;

[0008] According to the charge ratio characteristics in the first mass spectrometry data, a second atmospheric open ion source is switched to ionize the residual material on the sample adsorbent material, and the ionized residual material is introduced into a tandem mass spectrometer for analysis, outputting second mass spectrometry data;

[0009] matching the second mass spectrum data with a preset mass spectrum database, and outputting a detection result corresponding to the mass spectrum data.

[0010] In some embodiments, the ionization of the residue on the sample adsorption material by the second normal-pressure open ion source according to the charge ratio characteristics of the first mass spectrum data comprises:

[0011] determining a second normal-pressure open ion source corresponding to the first mass spectrum data according to the charge ratio characteristics of the first mass spectrum data, wherein the second normal-pressure open ion source comprises a direct analysis in real time ion source (DART), a desorption electrospray ionization ion source (DESI) or a low temperature plasma probe (LTP);

[0012] switching to the second normal-pressure open ion source, and ionizing the residue on the sample adsorption material by the second normal-pressure open ion source according to ion source parameters corresponding to the charge ratio characteristics of the first mass spectrum data.

[0013] In some embodiments, when the second normal-pressure open ion source is switched to DART, the ion source parameters comprise: the excitation gas is nitrogen containing a dopant, the dopant comprises acetone vapor or ammonia gas with a volume content of 0.1% to 1%, the temperature ranges from 200°C to 500°C, the gas flow rate is 1 L / min to 5 L / min, and the distance between the sample adsorption material and the ion source nozzle is 3 mm to 10 mm.

[0014] In some embodiments, when the second normal-pressure open ion source is switched to DESI, the ion source parameters comprise: the spraying solvent is a methanol aqueous solution containing a molecularly imprinted polymer and 0.1% to 1% formic acid or acetic acid, the spraying voltage is 3 kV to 5 kV, and the solvent flow rate is 2 μL / min to 10 μL / min.

[0015] In some embodiments, when the second normal-pressure open ion source is switched to LTP, the ion source parameters comprise: the working gas is helium containing an anti-matrix interference agent, the discharge voltage is 2 kV to 5 kV, the discharge frequency is 10 kHz to 30 kHz, the gas flow rate is 0.5 L / min to 2 L / min, and the anti-matrix interference agent comprises carbon tetrafluoride gas with a volume content of 1%, oxygen with a volume content of 1% or argon with a volume content of 5%.

[0016] In some embodiments, the adsorption material is a polyester fiber, nylon or cellulose coated with polydimethylsiloxane on the surface.

[0017] In some embodiments, the organic solvent is methanol or acetonitrile containing a molecularly imprinted polymer.

[0018] In some embodiments, the method is suitable for detecting one or more of methamphetamine, cocaine, heroin, morphine, synthetic cannabinoids, ketamine, fentanyl, and a cathinone derivative on a surface.

[0019] Compared with the prior art, the present application has the following beneficial effects:

[0020] By placing the sample adsorption material in the excitation region of the first open ion source at atmospheric pressure, ionizing the residues on the sample adsorption material using the first open ion source at atmospheric pressure, introducing the ionized residues into the tandem mass spectrometer for analysis, and outputting the first mass spectrum data, the sample is first detected; according to the charge ratio characteristics in the first mass spectrum data, the second open ion source is switched to ionize the residues on the sample adsorption material, and the ionized residues are introduced into the tandem mass spectrometer for analysis, and the second mass spectrum data is outputted, according to the preliminary detection result, the second open ion source suitable for the preliminary detection result is used for result verification; the second mass spectrum data is matched with the preset mass spectrum database, and the detection result corresponding to the mass spectrum data is outputted, so as to ensure the accuracy of the detection result. DETAILED DESCRIPTION

[0021] To make the above objectives, features and advantages of the present application more apparent, the specific embodiments of the present application are described in detail below. In the following description, a large number of specific details are set forth in order to facilitate a thorough understanding of the present application. However, the present application can be implemented in many different ways other than those described herein, and those skilled in the art can make similar improvements without departing from the scope of the present application, therefore the present application is not limited to the specific embodiments disclosed below.

[0022] The term "prepared from" as used herein is synonymous with "comprising". As used herein the terms "comprise", "comprises" or "comprising" and the like are deemed to cover a non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that comprises a list of elements is not necessarily limited only to those elements but can include other elements not expressly listed or inherent to such composition, step, method, article, or apparatus.

[0023] When equivalent, concentration, or other value or parameter is expressed in a range, a preferred range, or a series of upper preferred values and lower preferred values, it is to be understood that the stated range or preferred range includes all ranges and preferred ranges formed by any upper value or upper preferred value and any lower value or lower preferred value, whether or not the range is explicitly disclosed. For example, if a range is stated as "1 to 5", the described range should be interpreted to include ranges of "1 to 4", "1 to 3", "1 to 2", "1 to 2 and 4 to 5", "1 to 3 and 5", etc. When numerical ranges are described herein, unless otherwise stated, the range is intended to include the end values and all integers and fractions within that range.

[0024] In addition, the indefinite articles "a" and "an" preceding an element or component of the application are intended to be construed to cover both the singular and the plural of the element or component, unless otherwise indicated by the context. Thus, "a" or "an" should be read to include one or at least one, and the singular also includes the plural unless it is obvious that it is meant otherwise.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0026] The application provides a method for detecting surface residual drugs by atmospheric open ion source tandem mass spectrometry, which is applied to an atmospheric open ion source tandem mass spectrometry detection system, the system comprising a direct analysis real-time ion source (DART), an electrospray desorption ion source (DESI), a low temperature plasma probe (LTP), a tandem mass spectrometer and a computer device, the computer device being used for data operation, ion source switching / working control and mass spectrometer working control.

[0027] The method comprises:

[0028] The sample adsorption material is obtained by wetting the adsorption material with an organic solvent and then wiping the surface of the object with the wet adsorption material to collect the residual substances on the surface of the object;

[0029] The sample adsorption material is placed in the excitation region of the atmospheric open ion source, the residual substances on the sample adsorption material are ionized by the first atmospheric open ion source, the ionized residual substances are introduced into the tandem mass spectrometer for analysis, and first mass spectrum data is outputted;

[0030] Switching to a second normal-pressure open ion source according to the charge ratio characteristics in the first mass spectrum data, ionizing residues on the sample adsorption material, and ionizing residues to be introduced into a tandem mass spectrometer for analysis, and outputting second mass spectrum data;

[0031] Matching the second mass spectrum data with a preset mass spectrum database, and outputting a detection result corresponding to the mass spectrum data.

[0032] In the method, the first normal-pressure open ion source can be a direct analysis real-time ion source (DART), an electrospray desorption ion source (DESI), or a low-temperature plasma probe (LTP). DART is suitable for detecting heat-stable compounds (such as methamphetamine, fentanyl, heroin, and khat), but is not suitable for detecting heat-unstable compounds (such as synthetic cannabinoids) or volatile drugs (such as GHB). DESI is suitable for detecting polar compounds (such as cocaine, morphine, synthetic cannabinoids (polar), and GHB), but is not suitable for detecting non-polar drugs (such as THC) or high-fat matrix samples. LTP is suitable for detecting heat-unstable compounds (such as synthetic cannabinoids, LSD, and fentanyl derivatives), but is not suitable for detecting high-boiling-point drugs or metal-doped samples. Therefore, the method first performs preliminary detection by using the first normal-pressure open ion source, and then according to the preliminary detection result, a second normal-pressure open ion source suitable for the preliminary detection result is used for result verification, so as to ensure the accuracy of the detection result.

[0033] More specifically, the adsorption material is a polyester fiber coated with polydimethylsiloxane. Polydimethylsiloxane can reduce the adsorption of polar impurities and reduce the interference of impurities in the sample. Polyester fiber, nylon, and cellulose belong to materials without background interference, and can avoid the generation of impurity peaks by the adsorption material.

[0034] More specifically, the organic solvent is methanol or acetonitrile containing a molecularly imprinted polymer. The molecularly imprinted polymer is a drug molecularly imprinted polymer, such as a methamphetamine imprinted polymer. Methanol and acetonitrile can enhance the adsorption capacity of drugs and improve the sampling efficiency and reliability.

[0035] More specifically, the surface residual drugs applicable to the method include one or more of methamphetamine, cocaine, heroin, morphine, synthetic cannabinoids, ketamine, fentanyl, and khat derivatives. According to the applicable objects of the normal-pressure open ion source, the method is applicable to the detection of multiple types of drugs and can ensure the accuracy of the results.

[0036] Further, a second ambient open ion source corresponding to the first mass spectrum data is determined according to the charge ratio characteristics of the first mass spectrum data, the second ambient open ion source including a direct analysis in real time ion source (DART), an electrospray desorption ion source (DESI) or a low temperature plasma probe (LTP), and the ionization of the residue on the sample adsorption material is performed by the second ambient open ion source according to the ion source parameters corresponding to the charge ratio characteristics of the first mass spectrum data.

[0037] The charge ratio characteristics of the first mass spectrum data represent possible drug types, for example, DART m / z 304 represents cocaine and DESI m / z 238 represents ketamine, and the mass spectrum charge ratio characteristics corresponding to each drug type can be obtained by experiments on a single known drug sample, which is not limited. The ion source parameters of the second ambient open ion source are automatically determined according to the drug type in this embodiment, so that the ion source parameters most suitable for the drug type are used for detection. The switching of the ion source can be realized by a rotary switching platform or a linear slide rail. For example, the ion source emitting ends of DART, DESI and LTP are fixed on a circular turntable of a rotary switching platform, and the ion source is switched by rotating the circular turntable driven by a motor; or DART, DESI and LTP are installed on a linear motor slide rail, and the ion source device is moved to switch the ion source by a position encoder.

[0038] Optionally, when the second ambient open ion source is switched to DART, the ion source parameters include: the excitation gas is nitrogen containing a dopant, the dopant includes acetone vapor or ammonia gas with a volume content of 0.1% to 1%, the temperature range is 200°C to 500°C, the gas flow rate is 1L / min to 5L / min, and the distance between the sample adsorption material and the ion source nozzle is 3mm to 10mm.

[0039] Nitrogen as the DART gas flow has the characteristics of low cost, and it can enhance the desorption efficiency of thermally stable compounds at high temperature; the introduction of acetone in the DART gas flow can promote the proton transfer reaction and enhance the [M+H] + signal; the introduction of ammonia can form an adduct ion ([M+NH4] + ) to enhance ionization.

[0040] Specifically, when the second ambient open ion source is switched to DART, the ion source parameters include: the excitation gas is nitrogen + 1% acetone, the temperature is 400°C, the gas flow rate is 4L / min, and the distance between the sample adsorption material and the ion source nozzle is 3mm. Acetone doping enhances the [M+H] + signal, high-temperature nitrogen rapid desorption, and 3mm distance ensures high sensitivity.

[0041] Optionally, when the second atmospheric open ion source is switched to DESI, the ion source parameters include: the spraying solvent is a methanol aqueous solution containing the molecularly imprinted polymer and 0.1% to 1% formic acid or acetic acid, the spraying voltage is 3 kV to 5 kV, and the solvent flow rate is 2 μL / min to 10 μL / min.

[0042] The molecularly imprinted polymer can specifically adsorb the target drug and inhibit ionization of interfering substances in a complex matrix; the acidic environment of formic acid or acetic acid promotes the generation of [M+H] + , and the methanol aqueous solution enhances the ionization efficiency of polar drugs.

[0043] Specifically, when the second atmospheric open ion source is switched to DESI, the ion source parameters include: the spraying solvent is a methanol aqueous solution (6:4) containing the molecularly imprinted polymer and 1% acetic acid, the spraying voltage is 3.5 kV, and the solvent flow rate is 3 μL / min.

[0044] Optionally, when the second atmospheric open ion source is switched to LTP, the ion source parameters include: the working gas is helium containing an anti-matrix interference agent, the discharge voltage is 2 kV to 5 kV, the discharge frequency is 10 kHz to 30 kHz, the gas flow rate is 0.5 L / min to 2 L / min, and the anti-matrix interference agent includes carbon tetrafluoride gas with a volume content of 1%, oxygen with a volume content of 1%, or argon with a volume content of 5%.

[0045] Helium has a low-temperature characteristic, can maintain the plasma temperature at 30°C to 60°C, avoids thermal instability drug degradation, and the He plasma can generate high-energy metastable atoms (He*), enhancing ionization efficiency; the introduction of carbon tetrafluoride gas in the LTP gas flow generates F - radicals, which can selectively digest biological matrices and reduce background noise matrix interference; oxygen can eliminate organic interference substances through oxidation reaction; and argon enhances plasma density.

[0046] Specifically, when the second atmospheric open ion source is switched to LTP, the ion source parameters include: the working gas is helium + 1% oxygen, the discharge voltage is 4 kV, the discharge frequency is 30 kHz, and the gas flow rate is 2 L / min.

[0047] Embodiment 1: DART ion source detects cocaine residue.

[0048] Test purpose: verify the detection sensitivity and selectivity of the DART ion source for cocaine residue under the condition of nitrogen doped with acetone vapor.

[0049] Test procedure: 1. Rub the PDMS coated polyester fiber (containing molecularly imprinted polymer) on a glass surface known to contain cocaine residue. 2. Place the sample sorbent material in the DART activation zone, parameters: nitrogen gas containing 0.5% acetone vapor, temperature 350°C, flow rate 3 L / min, distance 5 mm. 3. First mass spectral data (full scan mode) detected m / z 304 ([M+H] + ), switch to DART-MS / MS, parent ion m / z 304, daughter ions m / z 182, 82. 4. Match database confirms cocaine characteristic fragments.

[0050] Test results: m / z 304 signal intensity > 10 4 counts, signal to noise (S / N) > 50; MS / MS fragment match degree > 95%, limit of detection (LOD) 0.1 ng / cm 2 ; no false positive from interferent (caffeine).

[0051] Example 2: DESI ion source detects methamphetamine residue.

[0052] Test purpose: evaluate the ionization efficiency and anti-matrix interference ability of DESI for methamphetamine in methanol aqueous solution containing formic acid.

[0053] Test procedure: rub the surface of a plastic bag (containing methamphetamine residue), place the sample sorbent material in the DESI source. Ion source parameters: spray solvent is methanol: water (80:20) containing methamphetamine molecularly imprinted polymer and 0.5% formic acid, flow rate 5 μL / min, voltage 4 kV. First mass spectral data detected m / z 150 ([M+H] + ), switch to DESI-MS / MS, parent ion m / z 150, daughter ions m / z 91, 119.

[0054] Test results: m / z 150 signal intensity > 8 x 10 3 counts, S / N > 30. In a greasy matrix (fingerprint residue), methamphetamine can still be specifically identified (match degree 90%), LOD 0.5 ng / cm 2 .

[0055] Example 3: LTP ion source detects fentanyl residue.

[0056] Test purpose: verify the detection stability of LTP for fentanyl in helium containing carbon tetrafluoride.

[0057] Test procedure: wipe the surface of a banknote (containing fentanyl residue), sample sorbent placed in LTP source. Ion source parameters: helium with 1% CF4, voltage 3 kV, frequency 20 kHz, flow rate 1.5 L / min. First mass spectrum data detected m / z 337 ([M+H] + ), switched to LTP-MS / MS, parent ion m / z 337, daughter ions m / z 105, 188.

[0058] Test results: m / z 337 signal intensity stable (RSD <10%), S / N >40. Under the interference of banknote ink, fentanyl characteristic fragments are still clear (match degree 92%), LOD is 0.2 ng / cm 2 .

[0059] Example 4: Detection of mixed drug residues (DART switching DESI).

[0060] Test purpose: test the resolution ability of the method to mixed residues of heroin (m / z 370) and ketamine (m / z 238).

[0061] Test procedure: wipe the mixed residues on the table, first use DART (parameters same as case 1) to detect m / z 370 and 238. Switch to DESI (parameters same as example 2), MS / MS is performed on m / z 370 (daughter ion m / z 268) and m / z 238 (daughter ion m / z 125) respectively.

[0062] Test results: the ionization efficiency difference of the two drugs is <15%, no cross-inhibition. Database matching is all >90%, proving that the method is suitable for complex mixtures.

[0063] Example 5: Anti-interference verification (LTP with oxygen doping).

[0064] Test purpose: evaluate the anti-interference of LTP in oxygen-containing helium to cannabis residues (THC, m / z 315).

[0065] Test procedure: wipe the surface of leather (containing THC and perfume interference), LTP parameters: helium with 1% O2, other parameters same as case 3. MS / MS monitors m / z 315→193, 123.

[0066] Test results: perfume components (such as phthalate esters) do not interfere with THC fragment peaks. The LOD of THC is 0.3 ng / cm 2 , RSD <8% (n=5).

[0067] Any combination of the technical features in the above-described embodiments can be made, and for the sake of brevity, not all possible combinations are described, however, it is understood that the scope of the present disclosure encompasses all possible combinations.

[0068] The above-described specific embodiments have further detailed the purposes, technical solutions and beneficial effects of the present application, and it should be understood that the above-described is only for specific embodiments of the present application and is not used to limit the protection scope of the present application. It is particularly pointed out that any modification, equivalent replacement, improvement, etc. made by those skilled in the art within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for detecting surface residual drugs by atmospheric open ion source tandem mass spectrometry, characterized in that, The method comprises the following steps: a sample adsorption material is obtained by wetting an adsorption material with an organic solvent, and then wiping the surface of an object with the wet adsorption material to collect the residue on the surface of the object, wherein the organic solvent is methanol or acetonitrile containing a molecularly imprinted polymer, and the adsorption material is a polyester fiber coated with polydimethylsiloxane on the surface; the sample adsorption material is placed in an excitation region of an open ion source under normal pressure, and a first open ion source under normal pressure is used to ionize the residue on the sample adsorption material, and the ionized residue is introduced into a tandem mass spectrometer for analysis, and first mass spectrum data is output; based on the charge ratio characteristics in the first mass spectrum data, a second open ion source under normal pressure is switched to ionize the residue on the sample adsorption material, and the ionized residue is introduced into a tandem mass spectrometer for analysis, and second mass spectrum data is output; the second mass spectrum data is matched with a preset mass spectrum database, and a detection result corresponding to the mass spectrum data is output; the second open ion source under normal pressure is switched to ionize the residue on the sample adsorption material based on the charge ratio characteristics in the first mass spectrum data, comprising: based on the charge ratio characteristics of the first mass spectrum data, a second open ion source under normal pressure corresponding to the first mass spectrum data is determined, wherein the second open ion source under normal pressure includes a direct analysis real-time ion source (DART), an electro-spray desorption ion source (DESI) or a low temperature plasma probe (LTP); the second open ion source under normal pressure is switched, and the residue on the sample adsorption material is ionized by the second open ion source under normal pressure according to the ion source parameters corresponding to the charge ratio characteristics of the first mass spectrum data, wherein the charge ratio characteristics of the first mass spectrum data represent possible types of drugs, and the ion source parameters are ion source parameters most suitable for the possible types of drugs, and the switching of the ion source is realized based on a rotary switching platform or a linear slide rail.

2. The method of surface residual drug detection by atmospheric pressure open ion source tandem mass spectrometry according to claim 1, wherein, when the second open ion source under normal pressure is switched to DART, the ion source parameters include: the excitation gas is nitrogen containing a dopant, the dopant includes acetone vapor or ammonia gas with a volume content of 0.1% to 1%, the temperature range is 200°C to 500°C, the gas flow rate is 1L / min to 5L / min, and the distance between the sample adsorption material and the ion source nozzle is 3mm to 10mm.

3. The method of surface residual drug detection by atmospheric pressure open ion source tandem mass spectrometry of claim 1, wherein, when the second open ion source under normal pressure is switched to LTP, the ion source parameters include: the working gas is helium containing an anti-matrix interference agent, the discharge voltage is 2kV to 5kV, the discharge frequency is 10kHz to 30kHz, the gas flow rate is 0.5L / min to 2L / min, and the anti-matrix interference agent includes carbon tetrafluoride gas with a volume content of 1%, oxygen with a volume content of 1% or argon with a volume content of 5%.

4. The method of surface residual drug detection by atmospheric pressure open ion source tandem mass spectrometry of claim 1, wherein, the method is suitable for surface residual drugs including one or more of methamphetamine, cocaine, heroin, morphine, synthetic cannabinoids, ketamine, fentanyl and cocaethylene derivatives.