CN113680335B - Nanometer magnetic microsphere, preparation method thereof and application of nanometer magnetic microsphere in drug detection and metabolite thereof - Google Patents
Nanometer magnetic microsphere, preparation method thereof and application of nanometer magnetic microsphere in drug detection and metabolite thereof Download PDFInfo
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- 239000004005 microsphere Substances 0.000 title claims abstract description 58
- 238000001514 detection method Methods 0.000 title claims abstract description 53
- 229940079593 drug Drugs 0.000 title claims abstract description 45
- 239000003814 drug Substances 0.000 title claims abstract description 45
- 239000002207 metabolite Substances 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 238000002156 mixing Methods 0.000 claims abstract description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000002077 nanosphere Substances 0.000 claims abstract description 21
- XDLMVUHYZWKMMD-UHFFFAOYSA-N 3-trimethoxysilylpropyl 2-methylprop-2-enoate Chemical compound CO[Si](OC)(OC)CCCOC(=O)C(C)=C XDLMVUHYZWKMMD-UHFFFAOYSA-N 0.000 claims abstract description 10
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000002738 chelating agent Substances 0.000 claims abstract description 9
- 150000002433 hydrophilic molecules Chemical class 0.000 claims abstract description 9
- 239000003999 initiator Substances 0.000 claims abstract description 9
- 150000002634 lipophilic molecules Chemical class 0.000 claims abstract description 9
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 238000002604 ultrasonography Methods 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 3
- 239000000523 sample Substances 0.000 claims description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 231100000614 poison Toxicity 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- -1 MDA Chemical compound 0.000 claims description 7
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 6
- 239000003480 eluent Substances 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 6
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 5
- 229960003920 cocaine Drugs 0.000 claims description 5
- 150000002505 iron Chemical class 0.000 claims description 5
- 239000001632 sodium acetate Substances 0.000 claims description 5
- 235000017281 sodium acetate Nutrition 0.000 claims description 5
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2,2'-azo-bis-isobutyronitrile Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 4
- BEQZHFIKTBVCAU-UHFFFAOYSA-N 2-amino-2-(2-chlorophenyl)-1-cyclohexanone Chemical compound C=1C=CC=C(Cl)C=1C1(N)CCCCC1=O BEQZHFIKTBVCAU-UHFFFAOYSA-N 0.000 claims description 4
- SHXWCVYOXRDMCX-UHFFFAOYSA-N 3,4-methylenedioxymethamphetamine Chemical compound CNC(C)CC1=CC=C2OCOC2=C1 SHXWCVYOXRDMCX-UHFFFAOYSA-N 0.000 claims description 4
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 229940025084 amphetamine Drugs 0.000 claims description 4
- MSJMDZAOKORVFC-UAIGNFCESA-L disodium maleate Chemical compound [Na+].[Na+].[O-]C(=O)\C=C/C([O-])=O MSJMDZAOKORVFC-UAIGNFCESA-L 0.000 claims description 4
- 238000001819 mass spectrum Methods 0.000 claims description 4
- 229960001797 methadone Drugs 0.000 claims description 4
- 229960001252 methamphetamine Drugs 0.000 claims description 4
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims description 4
- 239000001509 sodium citrate Substances 0.000 claims description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 4
- ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 claims description 4
- 229940039790 sodium oxalate Drugs 0.000 claims description 4
- 239000006228 supernatant Substances 0.000 claims description 4
- AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 claims description 3
- DHJXZSFKLJCHLH-BMTFSNIDSA-N 369u7a6hxd Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@@]45[C@H]6[C@@H]([C@@]([C@H]31)(O)[C@@H](O)[C@@H]2OC)[C@H](OC)[C@@H]4[C@]([C@@H](C[C@@H]5OC)O)(COC)CN6CC)C(=O)C1=CC=CC=C1 DHJXZSFKLJCHLH-BMTFSNIDSA-N 0.000 claims description 3
- JJGYGPZNTOPXGV-SSTWWWIQSA-N 6-Acetylmorphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O JJGYGPZNTOPXGV-SSTWWWIQSA-N 0.000 claims description 3
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 3
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 claims description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 3
- DHJXZSFKLJCHLH-UHFFFAOYSA-N benzoylaconine Natural products CCN1CC(C(CC2OC)O)(COC)C3C(OC)C(C(C45)(O)C(O)C6OC)C1C32C4CC6(O)C5OC(=O)C1=CC=CC=C1 DHJXZSFKLJCHLH-UHFFFAOYSA-N 0.000 claims description 3
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 3
- 229960003529 diazepam Drugs 0.000 claims description 3
- 229960004207 fentanyl citrate Drugs 0.000 claims description 3
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 claims description 3
- 229960003299 ketamine Drugs 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 3
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 3
- 229960005181 morphine Drugs 0.000 claims description 3
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 claims description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 3
- 239000000176 sodium gluconate Substances 0.000 claims description 3
- 235000012207 sodium gluconate Nutrition 0.000 claims description 3
- 229940005574 sodium gluconate Drugs 0.000 claims description 3
- 239000001433 sodium tartrate Substances 0.000 claims description 3
- 229960002167 sodium tartrate Drugs 0.000 claims description 3
- 235000011004 sodium tartrates Nutrition 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 claims description 2
- 235000019982 sodium hexametaphosphate Nutrition 0.000 claims description 2
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 claims description 2
- WLLGXSLBOPFWQV-UHFFFAOYSA-N MGK 264 Chemical compound C1=CC2CC1C1C2C(=O)N(CC(CC)CCCC)C1=O WLLGXSLBOPFWQV-UHFFFAOYSA-N 0.000 claims 2
- 239000003607 modifier Substances 0.000 claims 1
- 239000012488 sample solution Substances 0.000 claims 1
- 239000003440 toxic substance Substances 0.000 claims 1
- 239000010865 sewage Substances 0.000 description 19
- 239000000203 mixture Substances 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 12
- 239000002574 poison Substances 0.000 description 11
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 239000008367 deionised water Substances 0.000 description 9
- 229910021641 deionized water Inorganic materials 0.000 description 9
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 7
- 238000001179 sorption measurement Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000007789 gas Substances 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000001132 ultrasonic dispersion Methods 0.000 description 5
- 239000003463 adsorbent Substances 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000000643 oven drying Methods 0.000 description 3
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 3
- 239000004810 polytetrafluoroethylene Substances 0.000 description 3
- 238000002203 pretreatment Methods 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NGBBVGZWCFBOGO-UHFFFAOYSA-N 3,4-Methylenedioxyamphetamine Chemical compound CC(N)CC1=CC=C2OCOC2=C1 NGBBVGZWCFBOGO-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 239000002117 illicit drug Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- KWTSXDURSIMDCE-OABOXVCPSA-N n,n,1,1,2-pentadeuterio-3-phenylpropan-2-amine Chemical group [2H]C([2H])C([2H])(N([2H])[2H])CC1=CC=CC=C1 KWTSXDURSIMDCE-OABOXVCPSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
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- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Electrochemistry (AREA)
- Physics & Mathematics (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention provides a nano magnetic microsphere, a preparation method thereof and application in drug and metabolite detection, wherein the preparation method comprises the following steps: (1) Mixing ferric salt with a chelating agent and an alkaline precipitant for reaction to obtain ferroferric oxide nanospheres; (2) Mixing the ferroferric oxide nanospheres obtained in the step (1) with a solvent by ultrasound, and then mixing with an alkaline regulator, tetraethyl orthosilicate and 3- (trimethoxysilyl) propyl methacrylate for reaction to obtain double bond modified magnetic silica microspheres; (3) And (3) mixing the double bond modified magnetic silica microsphere obtained in the step (2) with a hydrophilic compound, a lipophilic compound and an initiator for reaction to obtain the nano magnetic microsphere. The nano magnetic microsphere provided by the invention is simple to prepare, can be used for rapidly completing detection in drug detection, and is less in time consumption.
Description
Technical Field
The invention belongs to the field of drug detection, and particularly relates to a nano magnetic microsphere, a preparation method thereof and application in drug and metabolite detection, in particular to a nano magnetic microsphere with high detection speed, a preparation method thereof and application in drug and metabolite detection.
Background
The modern cities are numerous, the toxicity is complex, the characteristics of drug preparation and drug absorption in each area are different, drug poison and metabolites thereof are widely appeared in the sewage collection system, and the current situation and the change trend of the drug poison in sewage in most areas are not clear. The sewage analysis method can be used for evaluating the drug consumption of specific crowds (workplaces, schools, prisons and the like) in large areas (cities or countries) and small areas, and can obtain the variation trend of the type of the drug to be sucked or the information of novel drug types through short-term or long-term sampling detection. The monitoring result has higher reference value for developing works such as poison nest point searching, poison crime striking, new psychoactive substance early warning and the like.
At present, the research of the sewage analysis method mostly adopts an active sampling method, namely, the water sample is taken on site and then is brought back to a laboratory for pretreatment and analysis. The most commonly used pretreatment method is to extract the drug poison from the enriched water sample by solid-phase extraction (SPE). Because of the differences of physicochemical properties of different drug poisons, different types of solid phase extraction columns are used for enriching one or more drug poisons, wherein the solid phase extraction column with higher recovery rate and wider application has a hydrophilic lipophilic reversed phase adsorption extraction column Oasis HLB TM And cation exchange solid phase extraction column Oasis MCX TM Two, but the technology is used for processing multi-point large samples and has low content of drug poison,When urban sewage is interfered by complex matrixes, the time for manually treating one sample by the conventional column method is 2 hours, and the method has the characteristics of low reproducibility, long time consumption and high cost. Especially under the condition of a large number of sewage samples to be detected, the column method inevitably needs to be activated, buffered, leached, dried, eluted, nitrogen blown and fixed volume before the chromatographic analysis, and the time and economic cost are not small. Therefore, the conventional pretreatment method at present hardly meets the actual requirement of rapid analysis of trace or ultra trace of poison in urban sewage, and a scientific and efficient pretreatment method and a high-sensitivity detection instrument are urgently needed to establish a rapid analysis method of poison in sewage environment, so that necessary auxiliary tools are provided for preventing and striking poison crimes.
CN111426768A discloses an analysis method for simultaneously measuring 11 drugs and metabolites thereof in domestic sewage, which comprises the following steps: (1) preparing a solution; (2) sample pretreatment: thawing a sewage sample to room temperature, filtering the sewage sample by a glass fiber filter membrane, and adding the internal standard stock solution prepared in the step (1) into 50mL of domestic sewage sample for solid phase extraction; (3) And (3) respectively carrying out liquid chromatography-tandem mass spectrometry on the domestic sewage samples extracted in the step (2), and establishing an analysis method for simultaneously measuring 11 drugs and metabolites thereof in the domestic sewage. The method is expected to become an important tool for monitoring illegal drug consumption in the future, but still adopts liquid chromatography, sample pretreatment and detection for a long time.
Because the current drug detection in sewage needs a long time to obtain a detection result. Therefore, how to provide a drug detection method with short detection time becomes a problem to be solved.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a nano magnetic microsphere, a preparation method thereof and application in drug and metabolite detection, in particular to a nano magnetic microsphere with high detection speed, a preparation method thereof and application in drug and metabolite detection. The nano magnetic microsphere provided by the invention is simple to prepare, can be used for rapidly completing detection in drug detection, and is less in time consumption.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a method for preparing a nano-magnetic microsphere, the method comprising the steps of:
(1) Mixing ferric salt with a chelating agent and an alkaline precipitant for reaction to obtain ferroferric oxide nanospheres;
(2) Mixing the ferroferric oxide nanospheres obtained in the step (1) with a solvent by ultrasound, and then mixing with an alkaline regulator, tetraethyl orthosilicate and 3- (trimethoxysilyl) propyl methacrylate for reaction to obtain double bond modified magnetic silica microspheres;
(3) And (3) mixing the double bond modified magnetic silica microsphere obtained in the step (2) with a hydrophilic compound, a lipophilic compound and an initiator for reaction to obtain the nano magnetic microsphere.
The nano magnetic microsphere prepared by the specific method can effectively adsorb drugs and metabolites thereof in a sample to be detected, is favorable for subsequent detection, and greatly shortens the pretreatment time and the detection time of the sample.
Preferably, the mass ratio of the ferric salt to the chelating agent in the step (1) is (1-6): 0.2-6.
Preferably, the chelating agent in step (1) includes any one or a combination of at least two of sodium citrate, sodium maleate, sodium tartrate, sodium oxalate, sodium dihydrogen phosphate, sodium hexametaphosphate and sodium gluconate, for example, a combination of sodium citrate and sodium maleate, a combination of sodium tartrate and sodium oxalate, or a combination of sodium dihydrogen phosphate and sodium gluconate, etc., but not limited to the above-listed combinations, and other non-listed combinations within the above-listed ranges are equally applicable.
Preferably, the mass ratio of the ferric salt to the alkaline precipitant in the step (1) is (1-6): 4-16.
Preferably, the alkaline precipitant of step (1) comprises sodium acetate.
Preferably, the temperature of the reaction in step (1) is 160-220 ℃ and the time is 5-30h.
In the mass ratio of the iron salt to the chelating agent, the iron salt may be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, or the like, the chelating agent may be 0.2 parts, 0.5 parts, 1 parts, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5.5 parts, or 6 parts, or the like, the iron salt may be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, or 6 parts, or the like, the alkaline precipitant may be 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, or 16 parts, or the like, the reaction temperature may be 160 ℃, 170 ℃, 190 ℃, 200 ℃, 210 ℃, or 220 ℃ or the like, and the time may be 5 hours, 10 hours, 15 hours, 20 hours, 25 hours, 30 hours, or the like, but the present invention is not limited to the above-mentioned values, and the values are not limited to the above.
Preferably, the time of the ultrasonic treatment in the step (2) is 5-30min;
preferably, the ratio of the ferroferric oxide nanospheres, the alkaline regulator, the tetraethyl orthosilicate and the 3- (trimethoxysilyl) propyl methacrylate in the step (2) is (1-10), the ratio of the ferroferric oxide nanospheres in the step (2) is (2-8), the ratio of the ferroferric oxide nanospheres in the step (1-10) is (1-5) g/mL/mL/mL.
Preferably, the mass fraction of the alkaline regulator in the step (2) is 25-35%.
Preferably, the alkaline regulator of step (2) comprises ammonia and/or sodium hydroxide,
preferably, the temperature of the reaction in the step (2) is 20-30 ℃ and the time is 12-15h.
Wherein the time of the ultrasonic treatment can be 5min, 10min, 15min, 20min, 25min or 30min, and the like, the parts of the ferroferric oxide nanospheres can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, and the like, the parts of the alkaline regulator can be 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts or 8 parts, and the like, the parts of the tetraethyl orthosilicate can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, and the like, in the proportion of the ferroferric oxide nanospheres, the tetraethyl orthosilicate and the 3- (trimethoxysilyl) propyl methacrylate, the parts of 3- (trimethoxysilyl) propyl methacrylate may be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, etc., the mass fraction of the alkali regulator may be 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34% or 35%, etc., the reaction temperature may be 20 ℃, 21 ℃, 22 ℃, 23 ℃, 24 ℃,25 ℃, 26 ℃, 27 ℃, 28 ℃, 29 ℃ or 30 ℃ etc., the time may be 12 hours, 13 hours, 14 hours, 15 hours, etc., but the present invention is not limited to the above-mentioned values, and other values not mentioned in the above-mentioned value ranges are applicable as well.
The steps of the specific parameters can finish the preliminary modification of the microsphere surface, improve the subsequent modification effect of hydrophilic groups and lipophilic groups, and improve the adsorption effect on drugs and metabolites thereof.
Preferably, the hydrophilic compound in step (3) includes any one or at least two of vinyl pyrrolidone, methacrylic acid and glycidyl methacrylate, for example, a combination of vinyl pyrrolidone and methacrylic acid, a combination of methacrylic acid and glycidyl methacrylate, or a combination of vinyl pyrrolidone and glycidyl methacrylate, etc., but not limited to the above-listed combinations, and other combinations not listed in the above-listed combination range are equally applicable.
Preferably, the lipophilic compound of step (3) comprises divinylbenzene and/or styrene.
Preferably, the initiator of step (3) comprises 2, 2-azobisisobutyronitrile and/or benzoyl peroxide.
Preferably, the proportion of the double bond modified magnetic silica microsphere, the hydrophilic compound, the lipophilic compound and the initiator in the step (3) is (1-5): 1-7.2): 0.2-0.8 g/mL/mL/g.
Preferably, the temperature of the reaction in step (3) is 40-80 ℃ and the time is 5-10h.
In the proportion of the double bond modified magnetic silica microsphere, the hydrophilic compound, the lipophilic compound and the initiator, the proportion of the double bond modified magnetic silica microsphere can be 1 part, 2 parts, 3 parts, 4 parts or 5 parts, the proportion of the hydrophilic compound can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts or 7.2 parts, the proportion of the lipophilic compound can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts or 7.2 parts, and the like, the proportion of the initiator can be 0.2 part, 0.3 part, 0.4 part, 0.5 part, 0.6 part, 0.7 part or 0.8 part, and the like, the reaction temperature can be 40 ℃, 50 ℃,60 ℃, 70 ℃ or 80 ℃ and the like, and the reaction time can be 5h and 6h.7h, 8h, 9h, 10h, etc., but are not limited to the values recited above, and other values not recited in the above ranges are equally applicable.
The specific parameters and the reactant ratio can improve the adsorption effect of the prepared nano magnetic microsphere on drugs and metabolites thereof, reduce the pretreatment time of a sample to be detected and improve the detection accuracy.
In a second aspect, the present invention provides a nano magnetic microsphere prepared by the preparation method of the nano magnetic microsphere.
In a third aspect, the invention provides the use of a nanomagnetic microsphere as described above for detecting drugs and their metabolites.
In a fourth aspect, the present invention also provides a method for detecting drugs and metabolites thereof in a water body, the method comprising the steps of:
(1') mixing a sample to be detected with an internal standard and the nano magnetic microsphere, and magnetically separating to obtain an adsorbed nano magnetic microsphere;
and (2 ') mixing the adsorbed nano magnetic microsphere obtained in the step (1') with an eluent, magnetically separating, taking supernatant to remove and re-dissolve to obtain a sample injection, and then carrying out mass spectrum detection to obtain a detection result.
According to the detection method, drugs and metabolites thereof in the sample to be detected are adsorbed by the nano magnetic microspheres, and then eluted and detected by mass spectrometry, so that the sample pretreatment time and the detection time are greatly shortened on the premise of ensuring the accuracy, and the detection efficiency is improved.
Preferably, the drugs and metabolites thereof include amphetamine, methamphetamine, O 6 -any one or a combination of at least two of monoacetylmorphine, morphine, ketamine, norketamine, cocaine, benzoylaconine, MDA (3, 4-methylenedioxyamphetamine), MDMA (3, 4-methylenedioxymethamphetamine), carboximine, mecamylone, fentanyl citrate, diazepam, esczol or methadone, examplesSuch as, but not limited to, combinations of amphetamine and methamphetamine, norketamine and cocaine, or combinations of cassiteritone and cocaine, and the like, as well as other combinations not listed within the above ranges.
Preferably, the internal standard is a deuterated of the drug and its metabolites.
Preferably, the liquid-to-material ratio of the sample to be detected and the nano magnetic microspheres in the step (1') is (50-200): 20-40 mL/mg.
Preferably, the mixing time of step (1') is 20-30min.
Preferably, the eluent in step (2') includes any one or a combination of at least two of acetonitrile, n-hexane or acetone, for example, a combination of acetonitrile and n-hexane, a combination of n-hexane and acetone or a combination of acetonitrile and acetone, etc., but is not limited to the above-listed combinations, and other non-listed combinations within the above-listed combinations are equally applicable.
Preferably, the mixing time of step (2') is 10-20min.
Preferably, the concentration of the internal standard in the sample injection liquid in the step (2') is 230-270ng/mL.
In the liquid-material ratio of the sample to be measured and the nano magnetic microsphere, the part of the sample to be measured can be 50 parts, 60 parts, 70 parts, 80 parts, 90 parts, 100 parts, 110 parts, 120 parts, 130 parts, 140 parts, 150 parts, 160 parts, 170 parts, 180 parts, 190 parts or 200 parts, etc., the part of the nano magnetic microsphere can be 20 parts, 25 parts, 30 parts, 35 parts or 40 parts, etc., the mixing time in the step (1 ') can be 20min, 22min, 24min, 26min, 28min or 30min, etc., the mixing time in the step (2') can be 10min, 12min, 14min, 16min, 18min or 20min, etc., the concentration of the internal standard in the sample injection can be 230ng/mL, 240ng/mL, 250ng/mL, 260ng/mL or 270ng/mL, etc., but not limited to the above-listed values, and other non-listed values in the above numerical ranges are equally applicable.
Compared with the prior art, the invention has the following beneficial effects:
the nano magnetic microsphere prepared by adopting a specific method can effectively adsorb drugs and metabolites thereof in a sample to be detected, is beneficial to the subsequent detection, and greatly shortens the pretreatment time and the detection time of the sample; the adsorption effect of the prepared nano magnetic microsphere on drugs and metabolites thereof can be improved by controlling specific parameters and reactant proportions, the pretreatment time of a sample to be detected is shortened, and the detection accuracy is improved; in addition, the invention also provides a detection method of drugs and metabolites thereof, which adopts the nano magnetic microspheres to adsorb the drugs and the metabolites thereof in the sample to be detected, then elutes and adopts a mass spectrum detection mode, so that the sample pretreatment time and the detection time are greatly shortened on the premise of ensuring the accuracy, and the detection efficiency is improved.
Detailed Description
In order to further describe the technical means adopted by the present invention and the effects thereof, the following describes the technical scheme of the present invention in combination with the preferred embodiments of the present invention, but the present invention is not limited to the scope of the embodiments.
In the following embodiments, a sample to be measured is taken from a sewage pump station;
the internal standard is amphetamine-D5, methamphetamine-D5 and O 6 monoacetylmorphine-D3, morphine-D3, ketamine-D4, norketamine-D4, cocaine-D3, benzoylaconine-D3, MDA-D4, MDMA-D4, carboximide-D5, mecamylamine-D5, fentanyl-D5, diazepam-D5, esczolam-D5, methadone hydrochloride-D10.
Preparation example 1
The preparation example provides a nano magnetic microsphere, which is prepared by the following steps:
(1) 1.5g of ferric chloride is dissolved into 70mL of ethylene glycol, 1.5g of sodium citrate is added, after stirring for 1 hour, 5g of sodium acetate is added, after stirring, the mixture is added into a polytetrafluoroethylene reaction kettle, and the mixture is put into an oven to react for 20 hours at 190 ℃. Cooling to 25deg.C, cleaning with deionized water, and oven drying at 60deg.C to obtain monodisperse superparamagnetic ferroferric oxide nanospheres (Fe) 3 O 4 ).
(2) Dispersing 5g of the monodisperse superparamagnetic ferroferric oxide nanospheres in 600mL of ethanol and 170mL of deionized water, performing ultrasonic dispersion for 18 minutes, adding 5mL of ammonia water (mass fraction is 30%), uniformly mixing, adding 5mL of tetraethyl orthosilicate and 3mL of 3- (trimethoxysilyl) propyl methacrylate, reacting at 25 ℃ for 13 hours, obtaining double bond modified magnetic silica microspheres, and drying at 60 ℃.
(3) The 3g double bond modified magnetic silica microspheres described above were dispersed in a 1000mL round bottom flask, 600mL acetonitrile was added, then 3mL divinylbenzene, 4mL vinylpyrrolidone and 0.5g 2, 2-azobisisobutyronitrile were added to the solution, and the mixture was mechanically stirred under nitrogen for reaction for 1 hour. Then, the temperature was set to 60 ℃, the mixture was allowed to react for 7 hours at the temperature, then magnetically separated, washed with deionized water and ethanol, and finally, the product was dried at 25 ℃ to obtain the nano-magnetic microsphere.
Preparation example 2
The preparation example provides a nano magnetic microsphere, which is prepared by the following steps:
(1) 0.5g of ferric chloride is dissolved into 70mL of ethylene glycol, 0.1g of sodium maleate is added, after stirring for 1 hour, 8g of sodium acetate is added, after stirring, the mixture is added into a polytetrafluoroethylene reaction kettle, and the mixture is put into an oven to react for 30 hours at 160 ℃. Cooling to 25deg.C, cleaning with deionized water, and oven drying at 60deg.C to obtain monodisperse superparamagnetic ferroferric oxide nanospheres (Fe) 3 O 4 ).
(2) Dispersing 1g of the monodisperse superparamagnetic ferroferric oxide nanospheres in 600mL of ethanol and 170mL of deionized water, performing ultrasonic dispersion for 5 minutes, adding 2mL of ammonia water (mass fraction of 25%), uniformly mixing, adding 1mL of tetraethyl orthosilicate and 1mL of 3- (trimethoxysilyl) propyl methacrylate, reacting for 15 hours at 20 ℃, obtaining double bond modified magnetic silica microspheres, and drying at 60 ℃.
(3) The above 1g double bond modified magnetic silica microspheres were dispersed in a 1000mL round bottom flask, 600mL acetonitrile was added, then 7.2mL styrene, 1mL methacrylic acid and 0.2g 2, 2-azobisisobutyronitrile were added to the solution, and the mixture was mechanically stirred under nitrogen for 2 hours. Then, the temperature was set to 40 ℃, the mixture was allowed to react for 9 hours at the temperature, then magnetically separated, washed with deionized water and ethanol, and finally, the product was dried at 25 ℃ to obtain the nano-magnetic microsphere.
Preparation example 3
The preparation example provides a nano magnetic microsphere, which is prepared by the following steps:
(1) 3g of ferric chloride is dissolved into 70mL of ethylene glycol, 3g of sodium oxalate is added, after stirring for 1 hour, 2g of sodium acetate is added, after stirring, the mixture is added into a polytetrafluoroethylene reaction kettle, and the mixture is put into an oven to react for 5 hours at 220 ℃. Cooling to 25deg.C, cleaning with deionized water, and oven drying at 60deg.C to obtain monodisperse superparamagnetic ferroferric oxide nanospheres (Fe) 3 O 4 ).
(2) 10g of the monodisperse superparamagnetic ferroferric oxide nanospheres are dispersed in 1000mL of ethanol and 230mL of deionized water, ultrasonic dispersion is carried out for 30 minutes, 8mL of sodium hydroxide (mass fraction is 35%) is added, 10mL of tetraethyl orthosilicate and 5mL of 3- (trimethoxysilyl) propyl methacrylate are added after uniform mixing, the mixture is reacted for 12 hours at 30 ℃, and double bond modified magnetic silica microspheres are obtained, and the mixture is dried at 60 ℃.
(3) The above 5g double bond modified magnetic silica microspheres were dispersed in a 1000mL round bottom flask, 700mL acetonitrile was added, then 1mL divinylbenzene, 7.2mL vinylpyrrolidone and 0.8g benzoyl peroxide were added to the solution, and the mixture was mechanically stirred under nitrogen for 1 hour. Then, the temperature was set to 60 ℃, the mixture was allowed to react for 5 hours at the temperature, then magnetically separated, washed with deionized water and ethanol, and finally, the product was dried at 25 ℃ to obtain the nano-magnetic microsphere.
Preparation example 4
The preparation example provides a nano magnetic microsphere, and the preparation method is the same as that of preparation example 1 except that the addition amounts of 10mL of divinylbenzene and vinyl pyrrolidone in the step (3) are respectively 10mL and 0.5 mL.
Preparation example 5
The preparation example provides a nano magnetic microsphere, and the preparation method is the same as that of preparation example 1 except that the addition amounts of 10mL of divinylbenzene and vinylpyrrolidone in the step (3) are respectively 0.5mL and 10 mL.
In the following examples, mass spectrometry detection parameters were as follows:
sample injection mode: acoustic drop ejection; sample injection volume: 25nL; the detection mode is as follows: MRM; scanning mode: scanning positive ions simultaneously; spray voltage: 3200V; the ion source is stable at 300 ℃; collision gas: helium gas. The curtain gas flow was 20psi and the atomizer gas and heating gas pressures (GS 1 and GS 2) were 90 and 45psi, respectively.
Example 1
The embodiment provides a detection method of drugs and metabolites thereof, which comprises the following specific steps:
50mL of a sample to be detected (underground sewage) is taken, and is directly analyzed and detected after being treated according to the following method:
using 20mg of the nano-magnetic microspheres obtained in preparation example 1, the nano-magnetic microspheres were added into a centrifuge tube containing 50mL of a sewage sample (containing an internal standard), and after 1 minute of ultrasonic dispersion, the nano-magnetic microspheres were subjected to vortex adsorption at 20℃for 20 minutes. Subsequently, a magnet was placed at the bottom of the centrifuge tube to separate the magnetic solid phase extraction adsorbent from the solution. After 30 seconds the solution became clear and the supernatant was carefully removed. The target was eluted from the magnetic solid phase extraction adsorbent by ultrasonic washing with 3mL of acetonitrile solution for 5 minutes, the eluate was rapidly blow dried with nitrogen at 60 ℃, reconstituted with 0.1mL of methanol solution and passed through a 0.22 μm filter to remove impurities, and finally 25nL of the solution (internal standard concentration 250 ng/mL) was injected into a mass spectrometry system for analysis.
Example 2
The embodiment provides a detection method of drugs and metabolites thereof, which comprises the following specific steps:
200mL of a sample to be detected (underground sewage) is taken, and is directly analyzed and detected after being treated according to the following method:
using 40mg of the nano-magnetic microspheres obtained in preparation example 2, the mixture was added to a centrifuge tube containing 200mL of a wastewater sample (containing an internal standard), and after 1 minute of ultrasonic dispersion, the mixture was subjected to vortex adsorption at 20℃for 30 minutes. Subsequently, a magnet was placed at the bottom of the centrifuge tube to separate the magnetic solid phase extraction adsorbent from the solution. After 30 seconds the solution became clear and the supernatant was carefully removed. The target was eluted from the magnetic solid phase extraction adsorbent by ultrasonic washing with 3mL of acetonitrile solution for 5 minutes, the eluate was rapidly blow dried with nitrogen at 60 ℃, reconstituted with 0.1mL of methanol solution and passed through a 0.22 μm filter to remove impurities, and finally 25nL of the solution (internal standard concentration 250 ng/mL) was injected into a mass spectrometry system for analysis.
Examples 3 to 5
Examples 3 to 5 provide a method for detecting drugs and metabolites thereof, respectively, and the steps are the same as example 1 except that the nano-magnetic microspheres obtained in preparation example 1 are replaced with the nano-magnetic microspheres obtained in preparation examples 3 to 5, respectively.
Comparative example 1
Shaking 50mL of water sample, regulating pH to 1-2 with concentrated hydrochloric acid, filtering with glass fiber filter membrane, adding 100 μl of deuterated internal standard working solution with concentration of 50ng/L, mixing, and transferring to activated stateIn the MCX solid phase extraction column, the loading flow rate is not more than 4mL/min, methanol is used for leaching, the leaching flow rate is not more than 4mL/min, the solid phase extraction column is vacuumized to be dried, 5% ammonia methanol solution with mass fraction of 4mL is used for eluting, the eluting flow rate is not more than 1mL/min, the eluent is collected, the eluent is placed on a concentrator for concentration at 45 ℃ until the concentration is nearly dry, and 0.1% formic acid aqueous solution with mass fraction of 250 mu L is added for uniform mixing, and the aqueous microporous filter membrane is used for filtering to obtain an extract of a sample of a detection material for instrument detection.
Summarizing detection results:
the results of the tests of examples 1 to 5 and comparative example 1 were summarized as follows:
the results show that the detection method provided by the invention has excellent effects; as can be seen from comparison of example 1 and comparative example 1, the accuracy of the detection method provided by the invention is equivalent to that of a conventional detection method, but the pretreatment steps of the sample of the method provided by the invention are simpler, the required time is shorter, the detection result can be obtained only through mass spectrum detection, the detection speed is greatly increased, and the detection efficiency is higher; comparing examples 1 and 4-5, it can be found that the adsorption capacity of the nano magnetic microsphere is stronger and the detection accuracy is higher within the preferred parameter range of the invention.
The applicant states that the present invention is illustrated by the above examples as well as methods for preparing the same and applications in detecting drugs and metabolites thereof, but the present invention is not limited to the above examples, i.e. it is not meant that the present invention must be practiced by relying on the above examples. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.
In addition, the specific features described in the above embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, various possible combinations are not described further.
Claims (20)
1. The application of the nano magnetic microsphere in detecting drugs and metabolites thereof is characterized in that the preparation method of the nano magnetic microsphere comprises the following steps:
(1) Mixing ferric salt with a chelating agent and an alkaline precipitant for reaction to obtain ferroferric oxide nanospheres;
(2) Mixing the ferroferric oxide nanospheres obtained in the step (1) with a solvent by ultrasound, and then mixing with an alkaline regulator, tetraethyl orthosilicate and 3- (trimethoxysilyl) propyl methacrylate for reaction to obtain double bond modified magnetic silica microspheres;
(3) Mixing the double bond modified magnetic silica microsphere obtained in the step (2) with a hydrophilic compound, an lipophilic compound and an initiator for reaction to obtain the nano magnetic microsphere;
the drug and the metabolite thereof comprise amphetamine, methamphetamine and O 6 -any one or a combination of at least two of monoacetylmorphine, morphine, ketamine, norketamine, cocaine, benzoylaconine, MDA, MDMA, carboximide, mecacoximide, fentanyl citrate, diazepam, eszolam or methadone;
the proportion of the ferroferric oxide nanospheres, the alkaline regulator, the tetraethyl orthosilicate and the 3- (trimethoxysilyl) propyl methacrylate in the step (2) is (1-10), the proportion of the ferroferric oxide nanospheres is (2-8), the proportion of the ferroferric oxide nanospheres is (1-10), the proportion of the ferroferric oxide nanospheres is (1-5) g/mL/mL/mL;
the hydrophilic compound in the step (3) is methacrylic acid;
the lipophilic compound in the step (3) is styrene.
2. The use according to claim 1, characterized in that the mass ratio of iron salt to chelating agent in step (1) is (1-6): 0.2-6.
3. The use of claim 1, wherein the chelating agent of step (1) comprises any one or a combination of at least two of sodium citrate, sodium maleate, sodium tartrate, sodium oxalate, sodium dihydrogen phosphate, sodium hexametaphosphate, or sodium gluconate.
4. The use according to claim 1, wherein the mass ratio of the iron salt to the alkaline precipitant in step (1) is (1-6): 4-16.
5. The use according to claim 1, wherein the alkaline precipitant of step (1) comprises sodium acetate.
6. The use according to claim 1, wherein the reaction in step (1) is carried out at a temperature of 160-220 ℃ for a time of 5-30h.
7. The use according to claim 1, wherein the time of the ultrasound of step (2) is 5-30 min.
8. The use according to claim 1, wherein the alkaline regulator of step (2) has a mass fraction of 25-35%.
9. The use according to claim 1, wherein the alkaline modifier of step (2) comprises ammonia and/or sodium hydroxide.
10. The use according to claim 1, wherein the reaction in step (2) is carried out at a temperature of 20-30 ℃ for a time of 12-15h.
11. The use according to claim 1, wherein the initiator of step (3) comprises 2, 2-azobisisobutyronitrile and/or benzoyl peroxide.
12. The use according to claim 1, wherein the ratio of double bond modified magnetic silica microspheres, hydrophilic compound, lipophilic compound and initiator in step (3) is (1-5): 1-7.2: (0.2-0.8) g/mL/g.
13. The use according to claim 1, wherein the reaction in step (3) is carried out at a temperature of 40-80 ℃ for a time of 5-10h.
14. The method for detecting the toxic substances and the metabolites thereof in the water body is characterized by comprising the following steps of:
(1') mixing a sample to be detected with an internal standard and the nano magnetic microsphere according to any one of claims 1 to 13, and then magnetically separating to obtain an adsorbed nano magnetic microsphere;
(2 ') mixing the adsorbed nano magnetic microsphere obtained in the step (1') with an eluent, then magnetically separating, taking supernatant to be desolventized and redissolved to obtain a sample injection, and then carrying out mass spectrum detection to obtain a detection result;
the drug and the metabolite thereof comprise amphetamine, methamphetamine and O 6 -any one or a combination of at least two of monoacetylmorphine, morphine, ketamine, norketamine, cocaine, benzoylaconine, MDA, MDMA, carboximide, mecacoximide, fentanyl citrate, diazepam, eszolam or methadone.
15. The method of claim 14, wherein the internal standard is a deuterated of the drug and its metabolites.
16. The method according to claim 14, wherein the liquid-to-material ratio of the sample to be tested to the nano-magnetic microspheres in the step (1') is (50-200): (20-40) mL/mg.
17. The method according to claim 14, wherein the mixing in step (1') is performed for a period of 20 to 30 minutes.
18. The method of claim 14, wherein the eluent in step (2') comprises any one or a combination of at least two of acetonitrile, n-hexane or acetone.
19. The method according to claim 14, wherein the mixing in step (2') is performed for a period of 10 to 20 minutes.
20. The method according to claim 14, wherein the concentration of the internal standard in the sample solution in step (2') is 230-270ng/mL.
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