CN117890459A - Quick screening method for illegally adding chemical drugs into foods based on MSRIT-MS/MS - Google Patents
Quick screening method for illegally adding chemical drugs into foods based on MSRIT-MS/MS Download PDFInfo
- Publication number
- CN117890459A CN117890459A CN202410072860.XA CN202410072860A CN117890459A CN 117890459 A CN117890459 A CN 117890459A CN 202410072860 A CN202410072860 A CN 202410072860A CN 117890459 A CN117890459 A CN 117890459A
- Authority
- CN
- China
- Prior art keywords
- ion
- probe
- sildenafil
- msrit
- vardenafil
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 238000000034 method Methods 0.000 title claims abstract description 32
- 239000000126 substance Substances 0.000 title claims abstract description 22
- 229940079593 drug Drugs 0.000 title claims abstract description 20
- 239000003814 drug Substances 0.000 title claims abstract description 20
- 238000004885 tandem mass spectrometry Methods 0.000 title claims abstract description 19
- 235000013305 food Nutrition 0.000 title claims abstract description 12
- 238000012216 screening Methods 0.000 title abstract description 12
- 238000005070 sampling Methods 0.000 claims abstract description 33
- 238000001514 detection method Methods 0.000 claims abstract description 21
- 239000011550 stock solution Substances 0.000 claims abstract description 15
- 239000012224 working solution Substances 0.000 claims abstract description 12
- 238000001819 mass spectrum Methods 0.000 claims abstract description 9
- 239000000523 sample Substances 0.000 claims description 80
- 150000002500 ions Chemical class 0.000 claims description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- -1 dtermine Chemical compound 0.000 claims description 23
- 239000007789 gas Substances 0.000 claims description 19
- 239000007788 liquid Substances 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 16
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 claims description 14
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- 238000004949 mass spectrometry Methods 0.000 claims description 10
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical class CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 claims description 9
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 claims description 8
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
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- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims description 7
- 229960003310 sildenafil Drugs 0.000 claims description 7
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- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims description 6
- 229960001252 methamphetamine Drugs 0.000 claims description 6
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 claims description 6
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 claims description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- LJUBVCQVNMLSTQ-UHFFFAOYSA-N 5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-propyl-4h-pyrazolo[4,3-d]pyrimidine-7-thione Chemical compound CCCC1=NN(C)C(C(N2)=S)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 LJUBVCQVNMLSTQ-UHFFFAOYSA-N 0.000 claims description 4
- 238000000889 atomisation Methods 0.000 claims description 4
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- 238000004806 packaging method and process Methods 0.000 claims description 4
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 claims description 4
- 239000007901 soft capsule Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- KTHQLYOWYJTHOD-UHFFFAOYSA-N 1-methyl-5-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC(=O)C=3N(C)N=C(CCC)C=3N=2)C(OCCC)=CC=C1S(=O)(=O)N1CCN(C)CC1 KTHQLYOWYJTHOD-UHFFFAOYSA-N 0.000 claims description 3
- GXUGEZIHENHAGP-UHFFFAOYSA-N 2-[2-ethoxy-5-(4-ethyl-4-oxidopiperazin-4-ium-1-yl)sulfonylphenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CC[N+]([O-])(CC)CC1 GXUGEZIHENHAGP-UHFFFAOYSA-N 0.000 claims description 3
- OPIJAYPVGDPKAA-UHFFFAOYSA-N 5-[2-ethoxy-5-[4-[4-ethoxy-3-(1-methyl-7-oxo-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl]sulfonylpiperazin-1-yl]sulfonylphenyl]-1-methyl-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCC1=NN(C)C(C(N=2)=O)=C1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N(CC1)CCN1S(=O)(=O)C(C=1)=CC=C(OCC)C=1C(N1)=NC(=O)C2=C1C(CCC)=NN2C OPIJAYPVGDPKAA-UHFFFAOYSA-N 0.000 claims description 3
- QGNIMKVVHAXCSK-VGOFRKELSA-N C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)CC)=C1 Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)CC)=C1 QGNIMKVVHAXCSK-VGOFRKELSA-N 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 claims description 3
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 3
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 3
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 3
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 3
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 claims description 3
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 claims description 3
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- 229960000516 bezafibrate Drugs 0.000 claims description 3
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 claims description 3
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- 229960001948 caffeine Drugs 0.000 claims description 3
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 3
- 229960003609 cathine Drugs 0.000 claims description 3
- 229960005217 dapoxetine Drugs 0.000 claims description 3
- USRHYDPUVLEVMC-FQEVSTJZSA-N dapoxetine Chemical compound C1([C@H](CCOC=2C3=CC=CC=C3C=CC=2)N(C)C)=CC=CC=C1 USRHYDPUVLEVMC-FQEVSTJZSA-N 0.000 claims description 3
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- 229960002003 hydrochlorothiazide Drugs 0.000 claims description 3
- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 claims description 3
- 229960004569 indapamide Drugs 0.000 claims description 3
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 3
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- 229960000395 phenylpropanolamine Drugs 0.000 claims description 3
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- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 claims description 3
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- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 claims description 2
- JIMWYJMUPCVOFA-QDPGVEIFSA-N (6r,12ar)-6-(1,3-benzodioxol-5-yl)-2-octyl-6,7,12,12a-tetrahydro-3h-pyrazino[1,2-b]$b-carboline-1,4-quinone Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)CCCCCCCC)=C1 JIMWYJMUPCVOFA-QDPGVEIFSA-N 0.000 claims description 2
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 claims description 2
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- WQSACWZKKZPCHN-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutan-1-amine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N)CC(C)C)CCC1 WQSACWZKKZPCHN-UHFFFAOYSA-N 0.000 claims description 2
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- KZFHUILKKFVOMB-UHFFFAOYSA-N 2-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-5-methyl-7-propyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCCC1=NC(C)=C(C(N2)=O)N1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CCO)CC1 KZFHUILKKFVOMB-UHFFFAOYSA-N 0.000 claims description 2
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- MDDMCAQUTIFYAH-UHFFFAOYSA-N 5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-(2-methylpropyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC=3C(CC(C)C)=NN(C)C=3C(=O)N=2)C(OCC)=CC=C1S(=O)(=O)N1CCN(C)CC1 MDDMCAQUTIFYAH-UHFFFAOYSA-N 0.000 claims description 2
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- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 claims description 2
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Abstract
The invention provides a MSRIT-MS/MS-based method for illegally adding chemical drugs into food for quick screening, which comprises the following steps: and obtaining optimized parameters of the multi-morphology lead-in-triple four-level tandem mass spectrometer end, preparing a standard stock solution and a standard working solution, and sampling and detecting. According to the invention, specific detection conditions and methods are designed aiming at the illegal addition of chemical drugs in 123 functional foods, so that the mass spectrum parameter with the best characteristic ion response value is obtained, the illegal addition of drugs in the functional foods can be rapidly and sensitively screened on site with high accuracy, the analysis of single-batch samples can be completed within 1 minute, the time consumption of operation steps and the whole analysis is reduced, the extraction and liquid phase separation of analysis samples are not needed, the analysis steps are simplified, and the time required by the analysis is shortened. The anti-jolt device can be used for realizing on-site detection on a vehicle. The specificity and the sensitivity are very high, the detection limit of ppb level can be reached, and the false positive and false negative rate can be well reduced.
Description
Technical Field
The invention relates to the technical field of mass spectrum rapid detection, in particular to a MSRIT-MS/MS-based method for illegally adding chemical drugs into foods for rapid screening.
Background
The MSRIT ion source mass spectrometry technology utilizes a polymorphic sample to be quickly led into an electrospray ion source (MSRIT-ESI) to replace an ion source (ESI source/APCI source) of a traditional mass spectrometer, abandons a chromatographic instrument in a conventional liquid chromatography-mass spectrometry technical method, finishes sample pretreatment to obtain a result by directly scraping the surface of an object to be detected or directly dipping the liquid of the object to be detected, can simultaneously detect a plurality of compounds at one time, greatly saves the overall time of mass spectrometry detection, and realizes quick detection and analysis. This technique separates the sampling, sample introduction and ionization steps independently, which allows sampling to be performed independently at a location remote from the mass spectrometry inlet. So that the size, shape, flatness, etc. of the sample will no longer be limited by the space near the mass spectrometry entrance. MSRIT ion source mass spectrometry techniques can be used with multiple brands of polytypic mass spectrometers.
With the expansion of the functional food market. Qualification of these products has become a significant challenge, and there is a strong need for effective analytical tools. At present, no method for rapidly introducing a polymorphic sample into an electrospray ion source (MSRIT-ESI) and detecting illegal addition components in functional foods by combining a mass spectrometer exists, and the invention provides a site rapid screening detection method based on MSRIT-MS/MS for detecting illegal addition components in functional foods, which is suitable for rapidly screening illegal addition medicines in functional foods on site.
Disclosure of Invention
The invention aims to provide a MSRIT-MS/MS-based method for quickly screening illegally added chemical drugs in food, which is characterized in that the method is used for directly sampling by a probe, entering mass spectrum detection without pretreatment, realizing high-flux detection, obviously shortening the detection time, being quick, sensitive and high in accuracy, reducing the operation steps and the time consumption of the whole analysis, and being suitable for quickly screening illegally added drugs in functional food on site.
In order to achieve the above purpose, the present invention proposes the following technical scheme: a method for illegally adding chemical drugs into foods based on MSRIT-MS/MS comprises the following steps:
Step one: obtaining optimized parameters of a multi-form lead-in triple quadrupole tandem mass spectrometer (MSRIT-MS/MS) end: scanning single standard working solution of each standard compound with the mass concentration of 1.0 mug/mL in ESI+ and ESI-modes respectively, obtaining the result that each compound responds to a [ M+H ] + or [ M-H ] - excimer ion peak with stronger response in ESI (+) or ESI (-) ionization mode, respectively selecting each compound characteristic excimer ion peak as a parent ion for secondary mass spectrometry, determining the fragment ion with the largest response value as a quantitative ion, determining the fragment ion with the largest secondary response as a qualitative ion, adjusting collision energy, determining the fragment ion with the largest response value as a quantitative ion, determining the fragment ion with the largest secondary response as a qualitative ion, and obtaining the mass spectrometry parameter with the best characteristic ion response value;
The mass spectrum ESI ion source parameters with the best response values are as follows: atomization gas pressure: 5psi; drying gas flow rate: 3L/min; capillary voltage: positive mode 4000V, negative mode 4000V; drying gas temperature: 300 ℃; the detection mode is as follows: multiple stress monitoring (MRM) mode; the mass scanning range is 100-1000 m/z;
Step two, preparing a standard stock solution and a standard working solution, wherein the process for preparing the standard stock solution comprises the following steps: weighing 10mg of each standard compound in a 10mL volumetric flask, adding methanol for dissolution, fixing the volume to a scale, and shaking uniformly to obtain a standard stock solution with the mass concentration of 1.0mg/mL, wherein the process for preparing the standard working solution comprises the following steps: diluting a proper amount of each standard stock solution to 1.0 mug/mL by using a methanol solution;
step three, sampling, namely dipping the surface of the sample by using a probe so that the probe occupies the object to be detected;
Step four, inserting the sampled probe into a multi-form leading-in ion source sample inlet of a mass spectrometer, wherein the ion source of the mass spectrometer is MSRIT-ESI ion source, rapidly desorbing the sample from the surface of the sampling probe by using a MSRIT-ESI ion source high-temperature thermal desorption principle, carrying the gasified sample to an ionization region by carrier gas, detecting by using a triple four-pole tandem mass spectrometer (MS/MS), and taking out the probe after the peak is ended;
Wherein the ion source end parameters are introduced in a multi-form: air flow temperature (temperature of temperature controller): 280 ℃; liquid flow rate (liquid pump flow rate): 150. Mu.L/h; electrospray solution: methanol: water (1:1/0.1% formic acid); gas flow setting: 1.6L/min, actual flow: 1.6L/min; gas pressure setting: 5psi, actual pressure: 2.16psi.
Further, in the present invention, the standard compound includes phenylpropanolamine, norpseudoephedrine, ephedrine, pseudoephedrine, methamphetamine, amphetamine, chlorphenazine, hydrochlorothiazide, methamphetamine, caffeine, dtex, cloxagliflozin, bupropion, phenamine, pravastatin, furosemide, N-didemethylphenamine, flufenamide, phenamine, N-nadmethyl-cemide, indapamide, benzphetamine, mo Xibu-triptyline, biphenamide, chlorphenamine, clobetadine, bezafibrate, bumetamide, lovastatin, simvastatin, rimazate, oxofenamide, sildenafil, guazamide, erythrophenamine, erythrodine, such as erythrodine, erythrophenamine, such as is, and other drugs, and is preferably one or more suitable for use in the treatment of various diseases, the pharmaceutical composition comprises a combination of at least one of propoxyphenyl thiodelphinidide, benazelamide, cinnarizine, rodafil carbonate, propoxyphenyl sildenafil, degazinylthiosildenafil, acetamidopetafil, 2-hydroxypropyl nortadalafil, acetovardenafil, propoxyphenyl hydroxydeluxiferin, propoxyphenyl thioideneamide, yohimbine, dapoxetine, N-desmethylerythrophenamide, normethylthiophenamide, N-t-butoxycarbonyl-N-desmethylerythrophenamide, N-ethyltadalafil, O-desmethylsildenafil, pyrazole N-desmethylsilfil, isobutylsilfil, sildenafil dimer impurity, vardenafil, sildenafil N-oxide, vardenafil N-oxide, 2-hydroxyethyl noradafilafil, valafil acetyl analogues, valafil, dydroxyphenamide, silfilafil, sildenafil, vinylideneamide, silfil, 14-bromoxyphenamide, sildenafil, 14-ethylsulfanilamide, and other pharmaceutical compositions and pharmaceutical compositions comprising the pharmaceutical compositions.
Further, in the present invention, the sample sampling method of the different forms in the third step is as follows:
tablet: cutting the sample with a disposable blade, and slightly scraping the cross section with a sampling probe;
powder: scraping the inner wall of the packaging bag by using a sampling probe directly to deposit a small amount of powder;
hard capsule: opening the capsule, pouring out the content, scraping a small amount of powder on the inner wall of the capsule shell;
Soft capsule: cutting the capsules by scissors, and dipping a small amount of effluent liquid;
Oral solution: 3. Mu.L of liquid was pipetted off by a pipette and dropped onto the needle ring of the sampling probe, and the solvent was allowed to evaporate to dryness.
Further, in the invention, after each sampling is completed, the sampling probe burns the probe ring by using a spray gun type lighter, the ring is burned to be red and then to the middle part of the probe, and then the ring is burned again to the probe ring, the whole process lasts for 5-10 seconds, and residual organic matters on the probe are clearly burned, and the probe is placed in methanol or acetonitrile for cooling and washing for standby.
The beneficial effects are that the technical scheme of the application has the following technical effects: the application fully utilizes the high-temperature thermal desorption principle of MSRIT-ESI, the sample is quickly desorbed from the surface of the sampling probe, and the gasified sample is brought to the ionization region by the carrier gas. During this process, some of the chemical species to be analyzed are separated from the sample matrix, and many matrices (e.g., diet tea) can char due to the high temperatures and become separated from the target analytes. The method does not require a pretreatment step for analyzing the sample, thereby simplifying the analysis step and shortening the time required for analysis. The characteristics of simple sampling and rapid sample injection enable the technology to have rapid detection capability, and the method is very suitable for rapid screening detection for chemical identification. Meanwhile, the application designs specific detection conditions and methods aiming at the illegal addition of chemical drugs in 123 functional foods, obtains mass spectrum parameters with the best characteristic ion response values, can rapidly, sensitively and accurately screen the illegal addition of drugs in the functional foods on site, can finish the analysis of single-batch samples within 1 minute, reduces the time consumption of operation steps and the whole analysis, and can eliminate complex extraction, purification and liquid phase separation of analysis samples based on MSRIT-ESI ion sources and triple quadrupole tandem mass spectrometers (MS/MS), thereby simplifying the analysis steps and shortening the time required by the analysis. The mass spectrometer size was small compared to conventional mass spectrometers (length. Times. Width. Times. Depth: 32 cm. Times. 39 cm. Times. 79 cm), MSRIT-MS/MS size was bump resistant. The method can be used for realizing on-site detection on the vehicle. The method can be used for screening and analyzing 123 chemical drugs on a commercially available illegally added sample, has very high specificity and sensitivity, can reach the detection limit of ppb level, and can well reduce the false positive and false negative rate.
It should be understood that all combinations of the foregoing concepts, as well as additional concepts described in more detail below, may be considered a part of the inventive subject matter of the present disclosure as long as such concepts are not mutually inconsistent.
The foregoing and other aspects, embodiments, and features of the present teachings will be more fully understood from the following description, taken together with the accompanying drawings. Other additional aspects of the invention, such as features and/or advantages of the exemplary embodiments, will be apparent from the description which follows, or may be learned by practice of the embodiments according to the teachings of the invention.
Drawings
The drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated in various figures may be represented by a like numeral. For purposes of clarity, not every component may be labeled in every drawing. Embodiments of various aspects of the invention will now be described, by way of example, with reference to the accompanying drawings, in which:
FIG. 1 is a schematic flow chart of the present invention.
FIG. 2 is a specific chromatogram of the present invention.
FIG. 3 shows a representative chromatogram of ephedrine detected positively in the present invention.
FIG. 4 is a graph showing the test results of example 4 of the present invention.
FIG. 5 is a graph showing the test results of example 4 of the present invention.
FIG. 6 is a graph showing the test results of example 4 of the present invention.
FIG. 7 is a graph showing the test results of example 4 of the present invention.
Detailed Description
For a better understanding of the technical content of the present invention, specific examples are set forth below, along with the accompanying drawings. Aspects of the invention are described in this disclosure with reference to the drawings, in which are shown a number of illustrative embodiments. The embodiments of the present disclosure need not be defined to include all aspects of the present invention. It should be understood that the various concepts and embodiments described above, as well as those described in more detail below, may be implemented in any of a number of ways, as the disclosed concepts and embodiments are not limited to any implementation. Additionally, some aspects of the disclosure may be used alone or in any suitable combination with other aspects of the disclosure.
Example 1
The single standard working solution of each compound with the mass concentration of 1.0 mug/mL is respectively scanned under the ESI+ mode and the ESI-mode, wherein each compound comprises 123 illegally added chemical substances. As a result, the [ M+H ] + or [ M-H ] - excimer ion peak with stronger response of each compound in ESI (+) or ESI (-) ionization mode is obtained, the characteristic excimer ion peak of each compound is selected as a parent ion for secondary mass spectrum analysis, the fragment ion with the largest response value is defined as a quantitative ion, the fragment ion with the largest secondary response value is defined as a qualitative ion, the collision energy is further optimized, the fragment ion with the largest response value is defined as a quantitative ion, the fragment ion with the largest secondary response value is defined as a qualitative ion, the mass spectrum parameter with the best characteristic ion response value is obtained, and the optimized mass spectrum parameter is as follows:
Atomization gas pressure: 5psi;
Drying gas flow rate: 3L/min;
capillary voltage: positive mode 4000V, negative mode 4000V;
drying gas temperature: 300 ℃;
The detection mode is as follows: multiple stress monitoring (MRM) mode;
TABLE 1 illegal addition of chemical drug Mass Spectrometry parameters
Example 2
A method for illegally adding chemical drugs into foods based on MSRIT-MS/MS comprises the following steps:
Preparing a standard stock solution and a standard working solution, wherein the process for preparing the standard stock solution comprises the following steps: weighing 10mg of each standard compound in a 10mL volumetric flask, adding methanol for dissolution, fixing the volume to a scale, and shaking uniformly to obtain a standard stock solution with the mass concentration of 1.0mg/mL, wherein the process for preparing the standard working solution comprises the following steps: diluting a proper amount of each standard stock solution to 1.0 mug/mL by using a methanol solution;
step three, sampling, namely dipping the surface of the sample by using a probe so that the probe occupies the object to be detected, wherein the tablet comprises the following components: cutting the sample with a disposable blade, and slightly scraping the cross section with a sampling probe;
powder: scraping the inner wall of the packaging bag by using a sampling probe directly to deposit a small amount of powder;
hard capsule: opening the capsule, pouring out the content, scraping a small amount of powder on the inner wall of the capsule shell;
Soft capsule: cutting the capsules by scissors, and dipping a small amount of effluent liquid;
oral solution: sucking 3 mu L of liquid by a pipette, dripping the liquid onto a needle ring of a sampling probe, and volatilizing the solvent until the solvent is dry;
Pressed candy: grinding, dissolving with methanol, sucking 3 μl of supernatant with a pipette, dripping onto needle ring of sampling probe, and volatilizing the solvent until it is dry;
Step four, the sampled probe is inserted into an ion source sample inlet of a mass spectrometer, the ion source of the mass spectrometer is MSRIT-ESI ion source, a sample is rapidly desorbed from the surface of the sampling probe by a MSRIT-ESI ion source high-temperature thermal desorption principle, the gasified sample is brought into an ionization region by carrier gas, a triple four-level rod tandem mass spectrometer (MS/MS) is used for detection, and the probe is taken out after the peak is ended;
Wherein the ion source end parameters: air flow temperature (temperature of temperature controller): 280 ℃; liquid flow rate (liquid pump flow rate): 150. Mu.L/h; electrospray solution: methanol: water (1:1/0.1% formic acid); gas flow setting: 1.6L/min, actual flow: 1.6L/min; gas pressure setting: 5psi, actual pressure: 2.16psi.
The detection limit is determined by adopting a standard definition S/n=3, but because the content of a sample with the real illegally added chemical drugs is generally higher, the sample is directly scraped for detection during analysis, the response values of all analytes are higher, and the abundance is more than 10 3, so that the relevant level of the illegally added substances in the food can be screened.
The method established by the embodiment is used for screening and analyzing 123 kinds of chemical drugs on a commercially available illegally added sample, the positive detection representative map is shown in figure 3, and the analysis on the actual sample proves that the method is simple and reliable and is suitable for screening and analyzing various illegally added chemical drugs in functional foods.
Example 3
Taking blank sample and reference solution, sampling positive samples 2 and 3, and measuring according to the above steps to obtain corresponding chromatograms, see figure 2. The results show that the blank sample has no interference, and the response of the control solution and the analyte to be detected in the sample is good.
Example 4
Specific application
The experimental process comprises the following steps:
1. sample preparation: the different sample forms were prepared as follows.
1. Tablet: cutting the sample with a disposable blade, and slightly scraping the cross section with a sampling probe;
2. powder: scraping the inner wall of the packaging bag by using a sampling probe directly to deposit a small amount of powder;
3. Hard capsule: opening the capsule, pouring out the content, scraping a small amount of powder on the inner wall of the capsule shell;
4. soft capsule: cutting the capsules by scissors, and dipping a small amount of effluent liquid;
5. Oral solution: sucking 3 mu L of liquid by a pipette, dripping the liquid onto a needle ring of a sampling probe, and volatilizing the solvent until the solvent is dry; 6. pressed candy: grinding, dissolving with methanol, sucking 3 μl of supernatant with a pipette, dripping onto needle ring of sampling probe, and volatilizing the solvent until it is dry;
2. preparation of standard solution:
1. Preparing a standard stock solution: accurately weighing phenylpropanolamine, norpseudoephedrine, ephedrine, pseudoephedrine, methamphetamine, chlorthiazide, hydrochlorothiazide, methamphetamine, caffeine, dtermine, lorcaserin, bupropion, fenfluramine, pravastatin, furosemide and N, N-didemethylsibutramine, fluoxetine, phenolphthalein, N-monodesmethylsibutramine, indapamide, sibutramine, benzyl sibutramine, haosaltretamine Mo Xibu, bisacodyl, closibutramine, bezafibrate, bumetanide, lovastatin, simvastatin, rimonabant, fenofibrate, orlistat, sildenafil, tadalafil, desulphated vardenafil, celebratinafil, nafac, benzamidinafil, amino tadalafil, tadalafil methyl chloride, benzothiadiafil, nardenafil, cabazitafil, pseudo-vardenafil, namediafil, N-deethyl vardenafil, N-desmethylsildenafil, erythronafil, hydroxy erythronafil, avanafil, idenafil, havemoxinafil, vardenafil, thiosildenafil, thiohamoxinafil, hydroxy vardenafil, hydroxy hamoxinafil, udenafil, hydroxy thiohamoxinafil, namofil, nifediafil, desmethyl tadalafil, chlordinafil, and chlordinafil hydroxy chlordanafil, N-butyl tadalafil, norcarbosildenafil, dimethyl erythrodenafil, dithio-desmethyl carbosildenafil, ketoerythrodenafil, N-octyl nortadalafil, diketopyrodenafil, hydroxy thiovardenafil, cyclopentafil, propoxyphenyl thiohydroxy deluximab, benazelate, cinquefoil, rodafil carbonate, propoxyphenyl sildenafil, degazinyl thiosildenafil, acetamidopetafil, 2-hydroxypropyl nortadalafil, acetovardenafil, propoxyphenyl hydroxyl deluxifen, propoxyphenyl thioideneafil, yohimbine, dapoxetine, N-desethylerythrofenamide, normethylthiosildenafil, N-t-butoxycarbonyl-N-desethylerythrofenamide, N-ethyl tadalafil, O-desmethylsildenafil, pyrazole N-desmethylsildenafil, isobutyl sildenafil, sildenafil dimer impurity, vardenafil N-oxide, 2-hydroxyethyl norlabetafil, valicarb analog, valafil dimer, nitrofil, thiofludarifen, sulfarenafil, 10mg of norbenazol, 14 mg of norbenazolin-ethyl-l, sildenafil, 14 mg of norbenazolin-ethyl, and other standard substances.
2. Mixing standard working solution: and respectively and accurately sucking a proper amount of each standard stock solution, and preparing the mixed standard working solution with the concentration of 1.0 mug/mL by using methanol.
3. Measurement conditions
Ion source end parameters:
a) Airflow temperature (temperature of temperature controller): 280 ℃;
b) Liquid flow rate (liquid pump flow rate): 150. Mu.L/h;
c) Electrospray solution: methanol: water (1:1/0.1% formic acid);
d) Gas flow setting: 1.6L/min, actual flow: 1.6L/min;
e) Gas pressure setting: 5psi, actual pressure: 2.16psi.
Mass spectrometer end parameters:
a) Atomization gas pressure: 5psi;
b) Drying air flow rate: 3L/min;
c) Capillary voltage: positive mode 4000V, negative mode 4000V;
d) Drying gas temperature: 300 ℃.
E) Qualitative ion pairs, quantitative ion pairs, and other mass spectral parameters are shown in table 1.
4. Sample measurement and measurement public security 10 batches of samples were collected on the market, and the measurement was performed according to the above method, and the results are shown in table 2. The results of the positive sample detection are shown in FIGS. 4-7.
TABLE 2 determination of actual samples
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While the invention has been described with reference to preferred embodiments, it is not intended to be limiting. Those skilled in the art will appreciate that various modifications and adaptations can be made without departing from the spirit and scope of the present invention. Accordingly, the scope of the invention is defined by the appended claims.
Claims (4)
1. A method for illegally adding chemical drugs into foods based on MSRIT-MS/MS is characterized by comprising the following steps: the method comprises the following steps:
Step one: obtaining optimized parameters of a multi-form lead-in triple quadrupole tandem mass spectrometer (MSRIT-MS/MS) end: scanning single standard working solution of each standard compound with the mass concentration of 1.0 mug/mL in ESI+ and ESI-modes respectively, obtaining the result that each compound responds to a [ M+H ] + or [ M-H ] - excimer ion peak with stronger response in ESI (+) or ESI (-) ionization mode, respectively selecting each compound characteristic excimer ion peak as a parent ion for secondary mass spectrometry, determining the fragment ion with the largest response value as a quantitative ion, determining the fragment ion with the largest secondary response as a qualitative ion, adjusting collision energy, determining the fragment ion with the largest response value as a quantitative ion, determining the fragment ion with the largest secondary response as a qualitative ion, and obtaining the mass spectrometry parameter with the best characteristic ion response value;
The mass spectrum ESI ion source parameters with the best response values are as follows: atomization gas pressure: 5psi; drying gas flow rate: 3L/min; capillary voltage: positive mode 4000V, negative mode 4000V; drying gas temperature: 300 ℃; the detection mode is as follows: multiple stress monitoring (MRM) mode; the mass scanning range is 100-1000 m/z;
Step two, preparing a standard stock solution and a standard working solution, wherein the process for preparing the standard stock solution comprises the following steps: weighing 10mg of each standard compound in a 10mL volumetric flask, adding methanol for dissolution, fixing the volume to a scale, and shaking uniformly to obtain a standard stock solution with the mass concentration of 1.0mg/mL, wherein the process for preparing the standard working solution comprises the following steps: diluting a proper amount of each standard stock solution to 1.0 mug/mL by using a methanol solution;
step three, sampling, namely dipping the surface of the sample by using a probe so that the probe occupies the object to be detected;
Step four, inserting the sampled probe into a multi-form leading-in ion source sample inlet of a mass spectrometer, wherein the ion source of the mass spectrometer is MSRIT-ESI ion source, rapidly desorbing the sample from the surface of the sampling probe by using a MSRIT-ESI ion source high-temperature thermal desorption principle, carrying the gasified sample to an ionization region by carrier gas, detecting by using a triple four-pole tandem mass spectrometer (MS/MS), and taking out the probe after the peak is ended;
Wherein the ion source end parameters are introduced in a multi-form: air flow temperature (temperature of temperature controller): 280 ℃; liquid flow rate (liquid pump flow rate): 150. Mu.L/h; electrospray solution: methanol: water (1:1/0.1% formic acid); gas flow setting: 1.6L/min, actual flow: 1.6L/min; gas pressure setting: 5psi, actual pressure: 2.16psi.
2. The method for illegally adding chemicals to a food based on MSRIT-MS/MS according to claim 1, wherein: the standard compound comprises phenylpropanolamine, norpseudoephedrine, ephedrine, pseudoephedrine, methamphetamine, amphetamine, chlorthiazine, hydrochlorothiazide, methamphetamine, caffeine, dtermine, lorcaserin, bupropion, fenfluramine, pravastatin, furosemide and N, N-didemethylsibutramine, fluoxetine, phenolphthalein, N-monodesmethylsibutramine, indapamide, sibutramine, benzylsibutramine, hao Mo Xibu-tramine, bisacodyl, closibutramine, bezafibrate, bumetanide, lovastatin, simvastatin, rimonabant, fenofibrate, orlistat, sildenafil, tadalafil, desulphated vardenafil, celedenafil, nafaretic acid, benzamidafil, amino tadalafil, tadalafil methyl chloride, benzothiadiafil, nardenafil, cabafil, pseudo-vardenafil, namediafil, N-deethyl vardenafil, N-desmethylsildenafil, erythronafil, hydroxy erythronafil, avanafil, idenafil, havemoxinafil, vardenafil, thiosildenafil, thiohamoxinafil, hydroxy vardenafil, hydroxy hamoxinafil, udenafil, hydroxy thiohamoxinafil, namofil, nifediafil, desmethyl tadalafil, chlordinafil, and chlordinafil hydroxy chlordanafil, N-butyl tadalafil, norcarbosildenafil, dimethyl erythrodenafil, dithio-desmethyl carbosildenafil, ketoerythrodenafil, N-octyl nortadalafil, diketopyrodenafil, hydroxy thiovardenafil, cyclopentafil, propoxyphenyl thiohydroxy deluximab, benzidenafil, cinnariafil, roflumilast carbonate, propoxyphenyl sildenafil, degazinyl thiosildenafil, acetamidoptadalafil, 2-hydroxypropyl nortadalafil, acetovardenafil, propoxyphenyl hydroxydeluxifen, propoxyphenyl thioidenafil, yohimbine, dapoxetine, N-desethyl erythrodenafil, northiosildenafil, N-t-butoxycarbonyl-N-desethyl erythrodenafil, N-ethyl tadalafil, O-desethyl sildenafil, pyrazole N-desmethyl sildenafil, isobutyl sildenafil, sildenafil dimer impurity, vardenafil piperazinone, sildenafil N-oxide, vardenafil N-oxide, 2-hydroxyethyl nortadalafil vardenafil acetyl analogues, vardenafil dimers, milrinafil, nitronafil, thiaquinate, amino sildenafil, desethyl carbadenafil, bisdecedinafil, N-phenylpropenyl tadalafil, N-desethyl-N-methyl vardenafil, thioidenafil, dichlorodenafil, prazonafil, propoxyphenyl thiosildenafil, propoxyphenyl thiohaamoxyfolafil, dithiodesethyl carbadenafil, hydroxythiored denafil, tadalafil dichloro impurity, sildenafil impurity 12, norpiperazinyl sildenafil sulphonic acid, propoxyphenyl idenafil, sildenafil impurity 14 and propoxyphenyl isobutyl idenafil.
3. The method for illegally adding chemicals to a food based on MSRIT-MS/MS according to claim 1, wherein: the sampling method of the samples with different forms in the third step is as follows:
tablet: cutting the sample with a disposable blade, and slightly scraping the cross section with a sampling probe;
powder: scraping the inner wall of the packaging bag by using a sampling probe directly to deposit a small amount of powder;
hard capsule: opening the capsule, pouring out the content, scraping a small amount of powder on the inner wall of the capsule shell;
Soft capsule: cutting the capsules by scissors, and dipping a small amount of effluent liquid;
Oral solution: 3. Mu.L of liquid was pipetted off by a pipette and dropped onto the needle ring of the sampling probe, and the solvent was allowed to evaporate to dryness.
4. The method for illegally adding chemicals to a food based on MSRIT-MS/MS according to claim 1, wherein: after each sampling is completed, the sampling probe burns the probe ring by using a spray gun type lighter, the ring is burned to be red and then to the middle part of the probe, and then the ring is returned to be burned to the probe ring, the whole process lasts for 5-10 seconds, and residual organic matters on the probe are clear through burning, and the probe is placed in methanol or acetonitrile for cooling and washing for standby.
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| CN112067685A (en) * | 2020-09-11 | 2020-12-11 | 兰州市食品药品检验所 | Method for rapidly detecting clenbuterol in meat through FaPEx-TD-ESI-MS/MS |
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| CN117405761A (en) * | 2022-07-06 | 2024-01-16 | 山东智谱检测科技有限公司 | MSRIT ion source automatic calibration detection device |
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