CN110346487A - ZIF-8@ SiO2Core-shell particles and its preparation method and application - Google Patents
ZIF-8@ SiO2Core-shell particles and its preparation method and application Download PDFInfo
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- CN110346487A CN110346487A CN201910652163.0A CN201910652163A CN110346487A CN 110346487 A CN110346487 A CN 110346487A CN 201910652163 A CN201910652163 A CN 201910652163A CN 110346487 A CN110346487 A CN 110346487A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000010420 shell particle Substances 0.000 title description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 71
- 239000013154 zeolitic imidazolate framework-8 Substances 0.000 claims abstract description 57
- MFLKDEMTKSVIBK-UHFFFAOYSA-N zinc;2-methylimidazol-3-ide Chemical compound [Zn+2].CC1=NC=C[N-]1.CC1=NC=C[N-]1 MFLKDEMTKSVIBK-UHFFFAOYSA-N 0.000 claims abstract description 57
- 229910052681 coesite Inorganic materials 0.000 claims abstract description 47
- 229910052906 cristobalite Inorganic materials 0.000 claims abstract description 47
- 229910052682 stishovite Inorganic materials 0.000 claims abstract description 47
- 229910052905 tridymite Inorganic materials 0.000 claims abstract description 47
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 37
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000004005 microsphere Substances 0.000 claims abstract description 34
- 238000002414 normal-phase solid-phase extraction Methods 0.000 claims abstract description 23
- 239000010410 layer Substances 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 18
- 239000002245 particle Substances 0.000 claims abstract description 15
- 239000011258 core-shell material Substances 0.000 claims abstract description 14
- 229940079593 drug Drugs 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 11
- 230000012010 growth Effects 0.000 claims abstract description 10
- 239000012621 metal-organic framework Substances 0.000 claims abstract description 10
- 239000000463 material Substances 0.000 claims abstract description 9
- 239000002344 surface layer Substances 0.000 claims abstract description 5
- 229910021536 Zeolite Inorganic materials 0.000 claims abstract description 4
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000010457 zeolite Substances 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 18
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 12
- IDYZIJYBMGIQMJ-UHFFFAOYSA-N enoxacin Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 IDYZIJYBMGIQMJ-UHFFFAOYSA-N 0.000 claims description 9
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 claims description 8
- 229960002549 enoxacin Drugs 0.000 claims description 8
- 235000012239 silicon dioxide Nutrition 0.000 claims description 8
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 claims description 7
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 claims description 6
- 238000005119 centrifugation Methods 0.000 claims description 6
- 229960003405 ciprofloxacin Drugs 0.000 claims description 6
- 229960000740 enrofloxacin Drugs 0.000 claims description 6
- 229960002422 lomefloxacin Drugs 0.000 claims description 6
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 claims description 6
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 3
- -1 amido modified silica Chemical class 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 229960001180 norfloxacin Drugs 0.000 claims description 3
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims 1
- 229920001577 copolymer Polymers 0.000 claims 1
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 7
- 238000009825 accumulation Methods 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 abstract description 3
- 239000011247 coating layer Substances 0.000 abstract description 2
- 238000004094 preconcentration Methods 0.000 abstract description 2
- 238000000605 extraction Methods 0.000 description 38
- 239000000523 sample Substances 0.000 description 25
- 238000011068 loading method Methods 0.000 description 19
- 239000000243 solution Substances 0.000 description 16
- 230000000694 effects Effects 0.000 description 14
- 238000010828 elution Methods 0.000 description 8
- 238000001514 detection method Methods 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 230000034655 secondary growth Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 5
- 239000003463 adsorbent Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 150000007660 quinolones Chemical class 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 239000012086 standard solution Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229960004273 floxacillin Drugs 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000001338 self-assembly Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- 238000007445 Chromatographic isolation Methods 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 238000009360 aquaculture Methods 0.000 description 1
- 244000144974 aquaculture Species 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 231100000693 bioaccumulation Toxicity 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003640 drug residue Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 235000008476 powdered milk Nutrition 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 239000013163 zeolitic imidazolate framework-82 Substances 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/08—Preparation using an enricher
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N2030/062—Preparation extracting sample from raw material
Abstract
The invention discloses a kind of ZIF-8@SiO2Core-shell particles are that have with SiO2Microballoon is core, using ZIF-8 as the complex microsphere of the nucleocapsid structure of shell.Accordingly, inventor has also set up corresponding preparation method, with SiO2Microballoon is core, first carries out carboxyl modified to it and obtains SiO2Then-COOH grows the metal organic framework ZIF-8 shell of zeolite type by alternate growth method layer by layer in its surface layer.Experiment shows, the complex microsphere of product of the present invention has the characteristics that controllable coating layer thickness, regular appearance, stability are strong, on-line solid phase extraction column is prepared as solid phase extraction material and is detected with high performance liquid chromatography combination for the on-line preconcentration to quinolone drugs, it is reproducible, batch reproducibility is high, there is preferable accumulation ability to quinolone drugs, and has the advantages that easy to operate, quick, efficient and use solvent few, therefore actual application prospect is extensive.
Description
Technical field
The invention belongs to solid phase extraction material technical field more particularly to a kind of ZIF-8@SiO2Core-shell particles and its system
Preparation Method and application.
Background technique
Quinolone antibiotics drug is a kind of synthetic antibacterial drug, has broad-spectrum antibacterial action, antibacterial action power strong, is mostly used
Make the anti-infectives of animal doctor's diagnosis and treatment and aquaculture, and plays good function and effect.Bacterium is to Comprecin
Congenital drug resistance resistant frequency it is extremely low, but acquired resistance rapidly develops, and quinolone antibiotics drug is easy to remain in
In animal body, because such antibiotic medicine cannot be absorbed and be metabolized to completely in animal body inactive substance discharge body
Outside, human body further can be entered by food chain, human health is damaged.There is also potential for quinolone antibiotics
Genetoxic and carcinogenicity threaten the health of people.
Solid phase extraction techniques (SPE) are to be adsorbed the target compound in fluid sample using solid absorbent, with sample
Matrix and chaff interferent separation reach separation and are enriched with a kind of Sample Pretreatment Technique of target compound purpose.Solid Phase Extraction tool
Have that sample transfer step is few, rate of extraction is fast, solvent consumption is few, the rate of recovery is high, favorable reproducibility, operating process is fast, safety and
The advantages that accuracy is high, especially online SPE is easy to operate, only need different channels switchings can reach example enrichment with separate
Coupling, reduces personal error to the full extent, shortens analysis time, has higher sensitivity, can be in food
It is applied in the analysis detection of drug residue.Adsorbent is the core of solid phase extraction techniques, and development has high selection to object
The novel solid phase extraction adsorbents of property and high bioaccumulation efficiency are the important research directions in sample pre-treatments field.
Metal organic framework (MOFs) one kind is self-assembly of by metal ion or metal cluster with organoligand coordination
Novel porous crystalline material, with large specific surface area, pore size is adjustable, have good stability, skeleton is modified after can carrying out, Yi Jikong
The advantages that road tactical rule, multiplicity, application of the MOFs in Solid Phase Extraction field have a good application prospect.However, tradition side
The MOFs grain shape of method synthesis is irregular, particle diameter distribution is wider or particle is thinner, and the column of the extraction column loaded presses through high, again
Existing property is poor.
Summary of the invention
The technical problem to be solved in the present invention is to provide the low ZIF-8@SiO of a kind of regular appearance, preparation cost2Nucleocapsid
Microballoon and its preparation method and application, products obtained therefrom have preferable accumulation ability to quinolone drugs.
In order to solve the above technical problems, the invention adopts the following technical scheme:
ZIF-8@ SiO2Core-shell particles are that have with SiO2Microballoon is core, using ZIF-8 as the compound of the nucleocapsid structure of shell
Microballoon.
Above-mentioned ZIF-8@SiO2Core-shell particles are Enoxacin, promise for being enriched with quinolone drugs, quinolone drugs
Flucloxacillin, Ciprofloxacin, Lomefloxacin, Enrofloxacin.
Above-mentioned ZIF-8@SiO2Core-shell particles are used as solid phase extraction material.
The on-line solid phase extraction column prepared with above-mentioned solid phase extraction material.
Above-mentioned on-line solid phase extraction column is for being enriched with quinolone drugs.
Above-mentioned ZIF-8@SiO2The preparation method of core-shell particles, with SiO2Microballoon is core, first carries out carboxyl modified to it and obtains
To SiO2Then-COOH grows the metal organic framework ZIF-8 of zeolite type by alternate growth method layer by layer in its surface layer
Shell.
Above-mentioned preparation method, comprising the following steps:
(1)SiO2Microsphere surface it is amido modified
In a heated condition, silicon dioxide microsphere and 3- aminopropyl triethoxysilane (APTES) are in N, N- dimethyl methyl
Back flow reaction in amide solution obtains amido modified silica SiO2-NH2；
(2)SiO2The carboxyl modified of microsphere surface
By step (1) resulting SiO2-NH2It is stirred to react in n,N-Dimethylformamide solution with maleic anhydride,
Obtain the silica SiO of carboxyl modified2-COOH。
(3)SiO2Microsphere surface grows ZIF-8 layer by layer
By step (2) resulting SiO2- COOH, which is added, contains Zn (NO3)2·6H2The methanol solution of O, back flow reaction, reaction
After be centrifuged, washed with methanol；The methanol solution containing 2-methylimidazole is added in centrifugation products therefrom, is centrifuged, uses after back flow reaction
Methanol washing, the growth of a shell is completed with regard to this；The step of this grows layer by layer is repeated to get complex microsphere.
In step (1): heating temperature is 80 DEG C, and silicon dioxide microsphere dosage is 3g, 3- aminopropyl triethoxysilane
(APTES) dosage is 3.48mL, and n,N-Dimethylformamide solution usage is 150mL, back flow reaction 12h.
In step (2): maleic anhydride dosage is 0.0123mol, and n,N-Dimethylformamide solution usage is
100mL is stirred to react 12h.
In step (3): containing Zn (NO3)2·6H2The methanol solution of O is 50mL, Zn (NO3)2·6H2O content is 2.35g；
Methanol solution containing 2-methylimidazole is 50mL, and 2-methylimidazole content is 6.48g；Back flow reaction 1h；Centrifugal rotational speed is
5000rpm, time are 10min；Repeat the step of this grows layer by layer five times or ten times.
Current metal organic framework (MOFs) and its preparation there are aiming at the problem that, inventor has developed a kind of ZIF-8
SiO2Core-shell particles are that have with SiO2Microballoon is core, using ZIF-8 as the complex microsphere of the nucleocapsid structure of shell.Accordingly, inventor
Corresponding preparation method is also set up, with SiO2Microballoon is core, first carries out carboxyl modified to it and obtains SiO2Then-COOH passes through layer
Metal organic framework ZIF-8 shell of the alternate growth method of layer in its surface layer growth zeolite type.Experiment shows that the present invention produces
The complex microsphere of product has the characteristics that controllable coating layer thickness, regular appearance, stability are strong, prepares as solid phase extraction material
On-line solid phase extraction column is simultaneously used for high performance liquid chromatography combination (SPE-HPLC) to quinolone drugs (Enoxacin, promise fluorine
Sha Xing, Ciprofloxacin, Lomefloxacin, Enrofloxacin) on-line preconcentration detection, it is reproducible, batch reproducibility is high, to quinolone
Class drug has preferable accumulation ability, and has the advantages that easy to operate, quick, efficient and few using solvent therefore real
Border application prospect is extensive.
Detailed description of the invention
Fig. 1 is ZIF-8@SiO of the present invention2The schematic illustration of the preparation method of core-shell particles.
Fig. 2 is ZIF-8@SiO produced by the present invention2The scanning electron microscope (SEM) photograph of complex microsphere, in figure: A is unmodified
SiO2Microballoon, B are the SiO that ZIF-8 has modified 5 thickness2Microballoon, C are the SiO that ZIF-8 has modified 10 thickness2Microballoon.
Fig. 3 is ZIF-8@SiO2The influence diagram that extraction column is enriched with quinolone medicine in different pH value.
Fig. 4 is ZIF-8@SiO2Extraction column is under different loading volumes to the concentration effect figure of quinolone medicine.
Fig. 5 is ZIF-8@SiO2Extraction column is under different elution times to the concentration effect figure of quinolone medicine.
Fig. 6 is ZIF-8@SiO2Extraction calibration graph of the extraction column to quinolone.
Fig. 7 is the quinolone standard solution direct injected of 500 μ g/L and the ZIF-8@SiO by different growth numbers2Extraction
The chromatogram of complex microsphere extraction, in figure: 1 Enoxacin, 2 Norfloxacins, 3 Ciprofloxacins, 4 Lomefloxacins, 5 Enrofloxacins.
Fig. 8 is ZIF-8@SiO2The repeatability and reproducibility of extraction column measures chromatogram, and in figure: A repeatability, B reproduce
Property, 1 Enoxacin, 2 Norfloxacins, 3 Ciprofloxacins, 4 Lomefloxacins, 5 Enrofloxacins.
Fig. 9 is ZIF-8@SiO2Extraction column stablizes figure to what 30 repetitions of quinolone extracted.
Specific embodiment
One, SiO2The preparation of@ZIF-8 core-shell particles
1, silicon dioxide microsphere surface is amido modified
Silicon dioxide microsphere 3g (2.5 μ m diameters, Aladdin), N,N-dimethylformamide (DMF) 150mL is taken to be placed in
In the round-bottomed flask of 250mL, 3- aminopropyl triethoxysilane is added dropwise in ultrasonic disperse 10min under magnetic stirring
(APTES) 3.48mL then heats to 80 DEG C, reacts 12h；Product centrifugation (5000rpm, 6min) after the reaction was completed, first uses DMF
It washes three times, then is washed three times with ethyl alcohol, product vacuum is dry, obtain amido modified silica (SiO2-NH2) about 3.3g.
2, the carboxyl modified on silicon dioxide microsphere surface
Take SiO2-NH2Powder 2.5g is scattered in the DMF of 40mL；Take maleic anhydride 0.0123mol (1.203g) molten
In the DMF of 40mL, SiO is added dropwise2-NH2Dispersion liquid in, be stirred to react 12h.(centrifugal condition is same for centrifugation after reaction
The first step), it is washed three times with DMF, repeats a second step reaction, product vacuum is dry, obtains the silica of carboxyl modified
(SiO2- COOH) about 2.9g.
3, silicon dioxide microsphere surface layer grows ZIF-8
Weigh SiO2- COOH powder 2.9g is placed in 250mL round-bottomed flask, is added and is contained 2.35g Zn (NO3)2·6H2O
50mL methanol solution, be warming up to 70 DEG C, back flow reaction 1h, after reaction be centrifuged (5000rpm, 10min), washed three times with methanol；
Centrifugation products therefrom is placed in the there-necked flask of 250mL, the methanol solution of 50mL 2-methylimidazole containing 6.48g is added to be warming up to 70 DEG C,
Reflux 1 hour is centrifuged (5000rpm, 10min) after reaction, is washed three times with methanol.The step of this grows layer by layer repeats 5
Or 10 times, gained centrifugation product is dried in vacuo, so that it may obtain the complex microsphere of 5 times and 10 secondary growths.
Two, the filling and activation of solid phase extraction column
By ZIF-8@SiO2Powder dries 12h at 120 DEG C, and the powder 100mg after taking drying is filled in SPE pillar,
SPE extraction column is mounted on the six-way valve of high performance liquid chromatography again, replaces the quantitative loop of six-way valve.
The activation of extraction column: HPLC sampling valve is placed at " Load ", and with accurate peristaltic pump loading, loading flow velocity is set as 1mL/
min.Pair pillar first is rinsed with 50mL water, then rinses pillar with 80mL methanol, finally rinses pillar with 30mL methanol again, i.e.,
The activation of SPE pillar finishes.
Three, on-line solid phase extraction
Self assembly ZIF-8@SiO of the present invention2The extraction detection process of on-line solid phase extraction column is as follows: preparing containing certain
The Enoxacin of concentration, Norfloxacin, Ciprofloxacin, Lomefloxacin, Enrofloxacin quinolone hybrid standard aqueous solution, loading
It is preceding first to use quinolone standard solution rinse sample feeding pipe；When loading, HPLC sampling valve is in " Load " state, by sample feeding pipe be inserted into
Sample mouth, with accurate peristaltic pump loading, loading flow velocity is 1mL/min；After loading, is eluted SPE system 18 seconds with water, wash away interference group
Divide and remain in standard sample unadsorbed in pipeline；When sample introduction, HPLC sampling valve is converted to " Inject " state, mobile phase
Analyte is eluted and makes it into highly effective liquid phase chromatographic system with 0.8mL/min back flush ZIF-8 extraction column and is analyzed
Detection, then recalls to " Load " state from " Inject " state for sampling valve, it is therefore an objective to which sample solution is compressed into a narrow spectrum
Into chromatographic column；After sample introduction, extraction column 10min is rinsed with acetonitrile, then be rinsed with water extraction column 3min, does standard for sample introduction next time
It is standby.Three groups of parallel laboratory tests are done under conditions of each loading volume.
Wherein, the selection of chromatographic condition is as follows:
It the use of chromatographic column is Eclipse Plus C18Column (5 μm, 4.6 × 150mm), flow rate of mobile phase 0.8mL/min,
Column temperature is 30 DEG C, and UV detector wavelength is 280nm.Mobile phase gradient is as follows:
1 mobile phase gradient of table
Four, ZIF-8 modification is to SiO2The influence of microsphere surface
To unmodified SiO2Microballoon and the complex microsphere that grown ZIF-8 shell have carried out scanning electron microscope analysis, obtain
As a result as shown in Figure 2.It can be seen that SiO from Fig. 2A2The surface smoother of ball, and grown the SiO of ZIF-82Microballoon (Fig. 2 B,
2C) surface is relatively rough, has short grained crystal to be evenly distributed in the surface of ball, and the diameter of ball significantly increases；Wherein grow
10 ZIF-8@SiO2The degree of roughness of microsphere surface is than grown 5 ZIF-8@SiO2The coarse journey of microsphere surface
It spends and also illustrates the ZIF-8@SiO that grown 10 times greatly2The amount of ZIF-8 is more on microballoon.
Five, the optimization of on-line solid phase extraction condition
The influence that 5.1 pH value are enriched with quinolone medicine
It is 1mL/min with loading speed, when loading volume is 1mL, measures ZIF-8 SiO2Extraction column is to different pH value
The enrichment condition of quinolone sample, as a result as shown in Figure 3.There is a carboxyl on the molecular structure of quinolone, is a kind of very weak
Acid, pKa1About 6, the pH value of solution will affect it and charge situation, to influence adsorbent to its adsorption effect, therefore optimize pH
Influence to extraction has very important effect.Since ZIF-8 material itself is positively charged, when pH value is greater than pKa1When, quinoline promise
Carboxyl on ketone molecule loses hydrogen ion, it is intended to negative point, at this moment become strong with the active force of ZIF-8 shell.It can from Fig. 3 result
Know, when the pH of sample is in the range of 1-7, the concentration effect of quinolone is increased with the raising of solution ph, and works as
Suction of the ZIF-8 to Enoxacin, Norfloxacin, Ciprofloxacin, Enrofloxacin these four quinolone antibiotics when sample pH value is 8
Attached ability decreases, and is still increasing the absorption of Lomefloxacin, still, can have to silicon dioxide microsphere under alkaline environment
Certain corrosivity will cause to damage to extraction column, therefore choosing optimal pH is 7.
Influence of 5.2 loading volumes to the concentration effect of quinolone medicine
Loading volume influence be applied sample amount number, using the quinolone solution of pH value=7, in the range of 2-6mL
Optimize loading volume.As can be seen from FIG. 4, when increasing in the range of loading volume is from 2mL to 5mL, with the increase of applied sample amount,
The extraction peak area of quinolone sample also increases, and when loading volume is higher than 5mL, the chromatographic peak area of sample reaches stable
Value illustrates that extraction column has reached balance to the adsorbance of 5 kinds of quinolones when loading volume is 5mL, therefore preferably applied sample amount is
5mL。
Influence of 5.3 elution times to the concentration effect of quinolone medicine
5 kinds of quinolone solution of selection pH=7, loading volume optimize mobile phase of high performance liquid chromatography under conditions of being 5mL
To the sample elution time adsorbed in solid-phase extraction column.Flow velocity with chromatographic isolation is 0.8mL/min, is elution rate, elution
Time is respectively 1min, 1.5min, 2min, 2.5min, 3min.As can be seen from FIG. 5, when the elution time of mobile phase is 2min
When, it will be able to the sample being enriched in extraction column is all eluted.Therefore, select elution time for 2min.The work of 5.4 standards
Curve
2 quinolone solution standard curve extracted of table
(pH=7, loading volume 5mL, elution time 2min) investigates ZIF-8@under the optimal conditions of above-mentioned optimization
SiO2The range of linearity that extraction column is enriched with 5 kinds of quinolones, as a result as shown in Fig. 6 and table 2.As can be known from the results, Enoxacin, promise
Flucloxacillin, Ciprofloxacin, Lomefloxacin, Enrofloxacin can be in good linear relationship, energy in the range of 10-2000 μ g/L
Enough quantitative determinations.
5.5 ZIF-8 grow influence of the number to concentration effect
ZIF-8@ SiO2The growth number of ZIF-8 will affect it in SiO on complex microsphere2The thickness of microsphere surface, thus
Influence the amount of adsorbent.The ZIF-8@SiO of 5 secondary growths and 10 secondary growths that are compared in experiment2Complex microsphere is to 500 μ g/L quinolines
The effect of extracting of promise ketone solution, chromatogram are as shown in Figure 7.Due to shell thickness difference, the rate eluted after absorption is variant, because
The ZIF-8@SiO of this 5 secondary growth and secondary growth2The retention time of two extraction post separations is variant.It can from upper result is schemed
Out, the resulting chromatographic peak very little of quinolone standard solution direct injected of 500 μ g/L, using the SiO of 5 secondary growths2@ZIF-8 is multiple
It closes microballoon and carries out the ZIF-8@SiO for extracting resulting chromatographic peak than 10 secondary growths2Complex microsphere carries out extracting resulting chromatographic peak
It is much smaller, the ZIF-8@SiO of 10 secondary growths can have been embodied2Complex microsphere has better concentration effect.More growths
Number is needing to expend more materials synthesis times, the ZIF-8@SiO of 10 secondary growths2The resulting concentration effect of complex microsphere
Analysis demand is can satisfy.
5.6 ZIF-8@ SiO2The enrichment times of extraction column
In order to calculate the enrichment times of SPE extraction pillar, by 20 μ L of quinolone standard solution direct injected, it is molten to measure standard
The standard curve of liquid.The calculation method of enrichment times is as follows, and the results are shown in Table 3.10 secondary growths as can be seen from the results
ZIF-8@ SiO2Extraction column enrichment times with higher, concentration effect are good.
The enrichment times of 3 SPE extraction column of table
The stability of 5.7 extraction columns
It is repeated to investigate its to continuous 6 enrichments of quinolone that same root extraction column is measured under the concentration of 500 μ g/L,
Gained chromatogram is as shown in Figure 8 A, and relative standard deviation (RSD) range of chromatographic peak area is 2.41-3.64%, illustrates ZIF-
8@ SiO2Extraction column has preferable repeatability.It is prepared for 3 ZIF-8@SiO in parallel under the same conditions2Extraction column investigates 3
Root extraction column is to the concentration effect (Fig. 8 B) of 500 μ g/L quinolone samples, and the RSD of gained chromatographic peak area is in 1.67-4.71%
In the range of, illustrate that the extraction column of preparation has preferable reproducibility.
By the peak area of measurement 30 times repetition extractions, as shown in Figure 9.30 repetition extractions have good stability, peak
The relative standard deviation of area is about 5%, illustrates ZIF-8@SiO2The stability that extraction column uses is good, long service life.
The measurement of 5.8 actual samples
By ZIF-8@SiO2Quinolone of the extraction column in actual sample milk powder carries out enrichment detection, as a result such as 4 institute of table
Show.When spiked levels are 100 μ g/L, the rate of recovery of 5 kinds of quinolones samples is in the range of 79.46-86.64%, explanation
Its enrichment that can be successfully applied to actual sample.
The detection of 4 powdered milk sample of table
Claims (10)
1. a kind of ZIF-8@SiO2Core-shell particles, it is characterised in that had with SiO2Microballoon is core, using ZIF-8 as the core-shell structure copolymer of shell
The complex microsphere of structure.
2. ZIF-8@SiO described in claim 12Core-shell particles are for being enriched with quinolone drugs, it is characterised in that: the quinoline promise
Ketone drug is Enoxacin, Norfloxacin, Ciprofloxacin, Lomefloxacin, Enrofloxacin.
3. ZIF-8@SiO described in claim 12Core-shell particles are used as solid phase extraction material.
4. the on-line solid phase extraction column prepared with solid phase extraction material described in claim 3.
5. on-line solid phase extraction column described in claim 4 is for being enriched with quinolone drugs.
6. ZIF-8@SiO described in claim 12The preparation method of core-shell particles, it is characterised in that: with SiO2Microballoon is core, first right
It carries out carboxyl modified and obtains SiO2Then-COOH grows zeolite type in its surface layer by alternate growth method layer by layer
Metal organic framework ZIF-8 shell.
7. preparation method according to claim 6, it is characterised in that the following steps are included:
(1)SiO2Microsphere surface it is amido modified
In a heated condition, silicon dioxide microsphere and 3- aminopropyl triethoxysilane return in n,N-Dimethylformamide solution
Stream reaction, obtains amido modified silica SiO2-NH2；
(2)SiO2The carboxyl modified of microsphere surface
By step (1) resulting SiO2-NH2It is stirred to react, obtains in n,N-Dimethylformamide solution with maleic anhydride
The silica SiO of carboxyl modified2-COOH；
(3)SiO2Microsphere surface grows ZIF-8 layer by layer
By step (2) resulting SiO2- COOH, which is added, contains Zn (NO3)2·6H2The methanol solution of O, back flow reaction, after reaction from
The heart is washed with methanol；The methanol solution containing 2-methylimidazole is added in centrifugation products therefrom, is centrifuged after back flow reaction, uses methanol
The growth of a shell is completed in washing with regard to this；The step of this grows layer by layer is repeated to get complex microsphere.
8. preparation method according to claim 7, it is characterised in that in step (1): heating temperature is 80 DEG C, silica
Microballoon dosage is 3g, and 3- aminopropyl triethoxysilane dosage is 3.48mL, and n,N-Dimethylformamide solution usage is
150mL, back flow reaction 12h.
9. preparation method according to claim 7, it is characterised in that in step (2): maleic anhydride dosage is
0.0123mol, n,N-Dimethylformamide solution usage are 80mL, are stirred to react 12h.
10. preparation method according to claim 7, it is characterised in that in step (3): containing Zn (NO3)2·6H2The first of O
Alcoholic solution is 50mL, Zn (NO3)2·6H2O content is 2.35g；Methanol solution containing 2-methylimidazole is 50mL, 2-methylimidazole
Content is 6.48g；Back flow reaction 1h；Centrifugal rotational speed is 5000rpm, and the time is 10min；Repeat the step of this grows layer by layer five times
Or ten times.
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