CN115078612B - Analysis method for detecting chemicals based on modified Cr-MOF - Google Patents
Analysis method for detecting chemicals based on modified Cr-MOF Download PDFInfo
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- 239000013087 chromium-based metal-organic framework Substances 0.000 title claims abstract description 59
- 238000004458 analytical method Methods 0.000 title claims abstract description 19
- 239000000126 substance Substances 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 21
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 17
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 17
- 238000002414 normal-phase solid-phase extraction Methods 0.000 claims abstract description 15
- 238000001514 detection method Methods 0.000 claims abstract description 13
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 11
- 239000006185 dispersion Substances 0.000 claims abstract description 9
- 239000002207 metabolite Substances 0.000 claims abstract description 9
- PMXMIIMHBWHSKN-UHFFFAOYSA-N 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCC(O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-UHFFFAOYSA-N 0.000 claims abstract description 6
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 claims abstract description 6
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229960004372 aripiprazole Drugs 0.000 claims abstract description 6
- 238000005516 engineering process Methods 0.000 claims abstract description 6
- 229960001534 risperidone Drugs 0.000 claims abstract description 6
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229960004431 quetiapine Drugs 0.000 claims abstract description 5
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 claims abstract description 5
- CDONPRYEWWPREK-UHFFFAOYSA-N 7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-1h-quinolin-2-one Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)C=CC4=CC=3)CC2)=C1Cl CDONPRYEWWPREK-UHFFFAOYSA-N 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 18
- 238000005406 washing Methods 0.000 claims description 13
- 229940001470 psychoactive drug Drugs 0.000 claims description 12
- 239000004089 psychotropic agent Substances 0.000 claims description 12
- 210000002966 serum Anatomy 0.000 claims description 12
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 10
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 claims description 10
- 239000007853 buffer solution Substances 0.000 claims description 10
- 239000006228 supernatant Substances 0.000 claims description 10
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 10
- 239000012498 ultrapure water Substances 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 235000019441 ethanol Nutrition 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 239000012071 phase Substances 0.000 claims description 6
- GVHCUJZTWMCYJM-UHFFFAOYSA-N chromium(3+);trinitrate;nonahydrate Chemical compound O.O.O.O.O.O.O.O.O.[Cr+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O GVHCUJZTWMCYJM-UHFFFAOYSA-N 0.000 claims description 5
- 230000007717 exclusion Effects 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 claims description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 3
- 239000005695 Ammonium acetate Substances 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 235000019257 ammonium acetate Nutrition 0.000 claims description 3
- 229940043376 ammonium acetate Drugs 0.000 claims description 3
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
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- 238000002360 preparation method Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 238000004729 solvothermal method Methods 0.000 claims description 3
- 238000004704 ultra performance liquid chromatography Methods 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 239000003643 water by type Substances 0.000 claims description 3
- -1 N-dealkylquetiapine Chemical compound 0.000 claims description 2
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 claims description 2
- 238000007664 blowing Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 238000000825 ultraviolet detection Methods 0.000 claims description 2
- 238000003556 assay Methods 0.000 claims 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims 1
- 235000011114 ammonium hydroxide Nutrition 0.000 claims 1
- 238000000605 extraction Methods 0.000 abstract description 22
- 230000000694 effects Effects 0.000 abstract description 20
- 239000000463 material Substances 0.000 abstract description 14
- 239000012472 biological sample Substances 0.000 abstract description 5
- 230000006920 protein precipitation Effects 0.000 abstract description 4
- 239000013178 MIL-101(Cr) Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 238000011084 recovery Methods 0.000 description 17
- 239000000523 sample Substances 0.000 description 15
- 239000003463 adsorbent Substances 0.000 description 7
- 238000001179 sorption measurement Methods 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000013177 MIL-101 Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000000622 liquid--liquid extraction Methods 0.000 description 3
- 239000012621 metal-organic framework Substances 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 238000000638 solvent extraction Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 239000000164 antipsychotic agent Substances 0.000 description 2
- 229940005529 antipsychotics Drugs 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
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- 238000001000 micrograph Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 238000000861 blow drying Methods 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
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- 230000006872 improvement Effects 0.000 description 1
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- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
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- 230000000607 poisoning effect Effects 0.000 description 1
- 239000013259 porous coordination polymer Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- 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
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
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- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention relates to an analysis method based on modified Cr-MOF detection chemicals, which utilizes a dispersion solid phase extraction technology, adopts modified Cr-MOF solid phase extraction to remove proteins in biological samples and enriches risperidone, quetiapine, aripiprazole and metabolites thereof, namely 9-hydroxy risperidone, N-dealkylquetiapine and dehydroaripiprazole, and carries out high performance liquid chromatography detection. According to the method, ethylenediamine is grafted on the basis of MIL-101 (Cr) to form modified Cr-MOF, so that the enrichment efficiency of risperidone, quetiapine, aripiprazole and metabolites thereof is improved, and meanwhile, proteins in a biological sample system are discharged, so that the step of protein precipitation is omitted. The method has the advantages of simple operation, time and cost saving of pretreatment, good extraction effect, cheap and easily available raw materials, environment-friendly application and wide market prospect, and the materials used by the method are expected to be special materials for biological sample extraction.
Description
Technical Field
The invention belongs to the field of chemical detection, and relates to an analysis method for detecting chemicals based on modified Cr-MOF.
Background
According to the current world health organization data, psychotic disorders (i.e., schizophrenia or bipolar disorder, manifested as hallucinations, delusions, or paranoid) affect approximately 8300 thousands of people worldwide. Thus, a series of antipsychotics have emerged that provide effective treatments for the symptoms of various psychosis. Antipsychotics can produce many side effects on the human body, the kinds of drugs, the doses consumed or individual differences of patients vary, but most have common side effects. Therefore, blood concentration monitoring is particularly important in psychiatry. Can be used for effectively and clinically managing patients receiving the treatment of the psychotropic drugs. Avoiding occurrence of medical complications, poisoning, unresponsiveness or non-compliance. Therefore, it is necessary to enhance the detection of psychotropic drugs in blood concentration monitoring.
The blood concentration monitoring refers to analyzing the concentration of the drug to be measured in blood by taking the principle of pharmacokinetics as a guide, so as to evaluate the curative effect or determine the dosing scheme, and individuating the dosing scheme to improve the treatment level of the drug and achieve the aim of clinical safe, effective and reasonable drug administration. Because serum contains a large amount of protein and the concentration of psychotropic drugs in blood is generally low, and patients often use other drugs, this may interfere with the analysis, the pretreatment method must have high selectivity and high sensitivity to accurately quantify and quantify the subsequent analysis. In the prior art, the pretreatment method for analyzing and detecting the psychotropic drugs by combining a pretreatment technology with high performance liquid chromatography mainly comprises liquid-liquid extraction (LLE), protein Precipitation (PP) and solid-phase extraction (SPE). At present, the commonly adopted liquid-liquid extraction method has the problems of excessive use of organic reagents, low extraction rate and the like; protein precipitation has the defects of low protein precipitation efficiency, easy blockage of high performance liquid chromatography, interference analysis of other medicines and the like; the solid phase extraction method has the defects of overlong extraction time, complicated steps (protein removal is needed before extraction), easy blockage of an extraction column, special equipment and the like.
Disclosure of Invention
The invention aims to overcome the defects of the prior art, designs an analysis method based on modified Cr-MOF detection chemicals, and utilizes a Dispersion Solid Phase Extraction (DSPE) technology, and simultaneously adopts modified Cr-MOF as a solid phase extraction material.
Dispersion Solid Phase Extraction (DSPE) is a novel sample pretreatment technology developed based on nanomaterials. In recent years, MOFs materials are introduced into a dispersion solid-phase extraction method by many researchers to serve as adsorbents, and the MOFs materials are porous coordination polymers self-assembled by metal ions and organic ligands through coordination bonds, and have the characteristics of large specific surface area, changeable and adjustable structure, stable chemical properties and the like.
In order to achieve the above object, the present invention provides an analytical method based on modified Cr-MOF detection chemistry: the method comprises the steps of removing protein from a serum sample to be detected by a dispersion solid phase extraction technology, enriching, and then carrying out ultraviolet detection to obtain the concentration of related medicines, and specifically comprises the following steps:
1) Adding the modified Cr-MOF into a centrifuge tube, adding buffer solution and serum into the centrifuge tube, swirling to uniformly disperse the modified Cr-MOF into a sample, centrifuging for 4-6min at 80000-10000r/min, and pouring out supernatant; wherein the ratio of the buffer solution to the serum is 4:1, a step of;
2) Adding an eluting solution into the precipitate in the step 1), swirling, fully eluting, centrifuging for 5min at 8000r/min, pouring the supernatant into a new centrifuge tube, blowing nitrogen to dry, re-dissolving by using a re-dissolving solution, dispersing uniformly, and detecting the prepared reaction system by using high performance liquid chromatography.
The preparation method of the modified Cr-MOF in the step 1) comprises the following steps:
S1, dissolving chromium nitrate nonahydrate and terephthalic acid in ultrapure water, dropwise adding 40% hydrofluoric acid aqueous solution by mass percent, and fully stirring to dissolve the chromium nitrate nonahydrate, the terephthalic acid, the ultrapure water and the hydrofluoric acid aqueous solution in a mass ratio of (80-90): (30-40): 1 (10-20);
S2, reacting the mixture prepared in the step 1) in a solvothermal reaction kettle at 210-230 ℃ for 7-9 hours, and washing the prepared mixture with DMF and hot ethanol;
S3, soaking the sample obtained in the step 2) in absolute ethyl alcohol for 18-22 hours, washing and drying after the reaction is finished, putting the sample into 30mmol/L ammonium fluoride solution for reacting for 9-11 hours at 58-62 ℃, washing with warm deionized water, and carrying out vacuum drying at 90-110 ℃ overnight to obtain the purified Cr-MOF;
S4, dissolving the purified Cr-MOF in absolute ethyl alcohol, continuously adding ethylenediamine, transferring into a reaction kettle for reaction, washing with ethanol for multiple times after the reaction is finished, and vacuum drying at 90-11 ℃ for 10-14h to obtain the modified Cr-MOF.
In step 1), the buffer solution is an acidic aqueous solution.
The pH value of the buffer solution is 3-5.
The eluting solution in the step 2) is methanol solution, methanol solution of acetic acid with volume ratio of 2%, acetonitrile or acetone.
The complex solution in the step 2) is acetonitrile water solution;
The volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 1:4.
The detection conditions of the high performance liquid chromatography in the step 2) are as follows: a column of waters ACQUity UPLC C18 mm.times.2.1 mm,1.7um was used; the detector is a diode array ultraviolet detector, and the measuring wavelength is 250nm; sample injection amount of the automatic sample injector: 20uL; the mobile phase A is: 975ml of ultrapure water +25ml of 2M ammonium acetate solution +1ml of formic acid +1ml of triethylamine, mobile phase B being acetonitrile.
The psychotropic drugs are risperidone, quetiapine, N-dealkylquetiapine, dehydroaripiprazole, aripiprazole and its metabolite 9-hydroxy risperidone.
In step S4, the reaction is shifted the reaction conditions in the kettle are as follows: reacting for 10-14h at 85-95 ℃.
The mass ratio of the purified Cr-MOF to the ethylenediamine in the step S4 is 50:1-2.
The invention has the following advantages:
The modified Cr-MOF material is adopted to have better adsorption efficiency on three mental drugs and metabolites thereof, the protein in a serum sample can be discharged in one step while the drugs are enriched, the protein removal step is saved, the modified Cr-MOF material is adopted as a dispersion solid phase extraction material, and a high performance liquid chromatography-ultraviolet detector is adopted, so that an analysis method of the three mental drugs and the metabolites thereof in the serum sample is established.
Drawings
FIG. 1 is a transmission electron microscope image of the Cr-MOF material MIL-101 and modified Cr-MOF of example 1.
FIG. 2 is an infrared plot of the Cr-MOF material MIL-101 and modified Cr-MOF of example 1.
FIG. 3 is a UV chromatogram of example 2 for labeling 6 psychotropic drugs.
FIG. 4 shows the effect of the amount of adsorbent used in example 4 on the extraction efficiency.
FIG. 5 shows the effect of pH of the buffer on the extraction effect in example 5.
FIG. 6 shows the effect of extraction time on the extraction effect in example 6.
FIG. 7 shows the effect of eluent type on extraction effect in example 7.
Detailed Description
The following examples further illustrate the invention, but are not intended to limit it.
Example 1
Preparation of modified Cr-MOF:
Firstly, 800mg of chromium nitrate nonahydrate and 332mg of terephthalic acid are dissolved in 9.5ml of ultrapure water, 0.1ml of hydrofluoric acid (40 w/w%) is added dropwise, and the mixture is fully stirred and dissolved; reacting the prepared mixture in a solvothermal reaction kettle at 220 ℃ for 8 hours, and washing the prepared mixture with DMF and hot ethanol after the reaction is finished;
soaking the washed material in absolute ethyl alcohol at 100 ℃ for 20 hours, washing and drying after the reaction is finished, then placing the material into 30mmol/L ammonium fluoride solution for reaction at 60 ℃ for 10 hours, washing with warm deionized water, and drying overnight at 100 ℃ in vacuum to obtain the purified Cr-MOF (MIL-101).
Weighing 0.3g of purified MIL-101, dissolving in 30ml of absolute ethyl alcohol, adding 0.18ml of ethylenediamine, transferring into a reaction kettle, reacting for 12 hours at 90 ℃, washing for many times with ethanol after the reaction is finished, and drying in vacuum at 100 ℃ for 12 hours to obtain the modified Cr-MOF.
As shown in FIGS. 1 and 2, FIG. 1 is a transmission electron microscope image of the obtained unmodified and modified Cr-MOFs, and FIG. 2 is an infrared image of the unmodified and modified Cr-MOFs.
Example 2
The modified Cr-MOF prepared in example 1 was used in this example for dispersion solid phase extraction.
Performing dispersion solid phase extraction by using modified Cr-MOF, the method is used for analyzing three psychotropic drugs and metabolites thereof in a biological sample by combining a high performance liquid chromatography, and comprises the following specific steps:
9mg of modified Cr-MOF is taken in a 1.5ml centrifuge tube, 800ml of buffer solution (PH=3) and 200ml of serum (the concentration of six kinds of psychotropic drugs in the total system is 200 ng/ml) are added into the centrifuge tube, vortex is carried out for 5min, the modified Cr-MOF is uniformly dispersed in a sample, 8000r/min is centrifuged for 5min, the supernatant is poured out, and the precipitate is reserved.
1Ml of 2% ammonia methanol solution is added into the precipitate, vortex is carried out for 8min, centrifugation is carried out for 5min at 8000r/min after full washing, the supernatant is poured into a new centrifuge tube, and after nitrogen blow drying, 1ml of ultrapure water is used: acetonitrile (80:20) is redissolved and dispersed uniformly, and the prepared reaction system is subjected to high performance liquid chromatography detection, wherein the conditions of the high performance liquid chromatography are as follows:
Detection conditions of high performance liquid chromatography: waters ACQUity UPLC C18 (50 mm. Times.2.1 mm,1.7 um) was used as column; the detector is a diode array ultraviolet detector, and the measuring wavelength is 250nm; sample injection amount of the automatic sample injector: 10ul. Mobile phase a (975 ml ultrapure water +25 2m ammonium acetate solution +1ml formic acid +1ml triethylamine), mobile phase B was acetonitrile, elution procedure as follows:
the results of the detection in this example are shown in the following table:
Example 3
The modified Cr-MOF was tested for protein exclusion effect:
Preparing 1mg/mL of bovine serum albumin solution to simulate serum environment, respectively weighing 9mg of modified Cr-MOF into a 1.5mL centrifuge tube, adding 1mL of bovine serum albumin solution, swirling for 5min, centrifuging for 5min at 8000r/min, and taking the supernatant into a new centrifuge tube.
Measuring protein in supernatant by Folin-phenol method, taking 0.25mL of solution in supernatant after enrichment centrifugation, placing in a test tube, adding 0.25mL of ultrapure water for dilution twice, adding 2.5mL of Folin-phenol reagent A, mixing uniformly, standing at room temperature for 10min, adding 0.25mL of Folin-phenol reagent B, mixing uniformly immediately, standing at room temperature for 30min, measuring absorbance value at 500nm wavelength, and calculating protein concentration in the sample system after enrichment according to a standard curve.
The modified Cr-MOF protein removal rate was calculated using the following formula:
BSA rejection(％)＝C0/Cf×100
Supernatant concentration after C 0 -SPE, initial concentration of C f-
The protein exclusion rate of the modified Cr-MOF is 92.93 percent, which shows that the modified Cr-MOF has better protein exclusion effect, and the protein exclusion in a serum sample system is performed outside the material while enriching the medicine, so that the step of precipitating the protein by using an organic solvent in the traditional solid phase extraction method is left.
Example 4
Effect of adsorbent usage on drug recovery:
This example investigated the effect of adsorbent usage on drug recovery. 3, 5, 7, 9, 11, 13 and 15mg of modified Cr-MOF are respectively weighed into 1mL of biological sample, and the concentration of six kinds of spirit in the sample is 200ng/mL. From the results of FIG. 4, it is understood that when the amount of modified Cr-MOF was increased from 1mg to 9mg, the recovery rate of risperidone, 9-hydroxyrisperidone, N-desmethylquetiapine, aripiprazole increased with the increase of the amount of the adsorbent, indicating that the adsorption sites increased and the adsorption amount increased with the increase of the amount of modified Cr-MOF; however, when the amount of the adsorbent is more than 9mg, the amount of modified Cr-MOF is increased, and the extraction recovery rate of risperidone, 9-hydroxyrisperidone, N-dealkylquetiapine and aripiprazole is decreased, and the recovery rate of dehydroaripiprazole is increased, so that the recovery rate of quetiapine is substantially unchanged, and the optimum amount of the extractant in the present invention is 9mg considering various factors.
Example 5
Effect of buffer pH on drug recovery:
this example investigated the effect of buffer pH on the surface adsorption site activity of the adsorbent. From the results of the extraction recovery rate under the conditions that the pH of the buffer solution is 3,5, 7, 9 and 11, respectively, it is known from the results of FIG. 5 that the recovery rates of the six psychotropic drugs are basically gradually reduced from pH 3 to pH 11; because the modified Cr-MOF is protonated under the acidic condition, electrostatic interaction is generated between the modified Cr-MOF and the alkaline medicine; the optimal pH of the extraction buffer is 3.
Example 6
Influence of extraction time on recovery of drug
The embodiment researches the influence of the extraction time on the recovery rate of the medicine, the extraction time can influence the adsorption balance between the medicine to be detected and the modified MOF material and influence the extraction recovery rate of the medicine, the invention examines the recovery rate conditions of six kinds of spirit when the extraction time is respectively 1,2, 5, 8 and 11min, as can be seen from the results of FIG. 6, when the extraction time was increased from 1min to 5min, all the drug recovery rates were increased, and after the extraction time was continued to be prolonged, the drug recovery rates were decreased except for a slight increase in 9-hydroxyrisperidone, indicating that the adsorption had reached equilibrium, so the optimal extraction time was 5min.
Example 7
Investigation of drug recovery by eluent species
In this example, the effect of different eluting solvents on the eluting efficiency of the drug to be tested adsorbed on the modified Cr-MOF was studied, and the effect of three pure organic solvents of methanol, acetonitrile and acetone on the extraction recovery rate was studied, and as shown in the results of fig. 7, methanol has the optimal eluting efficiency for three psychotropic drugs and their metabolites, so methanol was the optimal eluting solvent.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (9)
1. An analytical method for detecting chemicals based on modified Cr-MOF, which is characterized in that: the method comprises the steps of removing protein from a serum sample to be detected by a dispersion solid phase extraction technology, enriching, and then carrying out ultraviolet detection to obtain the concentration of related medicines, wherein the protein exclusion rate reaches 92.93 percent, and the method specifically comprises the following steps of:
1) Adding the modified Cr-MOF into a centrifuge tube, adding buffer solution and serum into the centrifuge tube, swirling to uniformly disperse the modified Cr-MOF into a sample, centrifuging for 4-6min at 80000-10000r/min, and pouring out supernatant; wherein the ratio of the buffer solution to the serum is 4:1, a step of;
2) Adding an eluting solution into the precipitate in the step 1), swirling, fully eluting, centrifuging for 5min at 8000r/min, pouring the supernatant into a new centrifuge tube, blowing nitrogen to dry, re-dissolving by using a re-dissolving solution, uniformly dispersing, and detecting the prepared reaction system by using high performance liquid chromatography;
The preparation method of the modified Cr-MOF in the step 1) comprises the following steps:
S1, dissolving chromium nitrate nonahydrate and terephthalic acid in ultrapure water, dropwise adding 40% hydrofluoric acid aqueous solution by mass percent, and fully stirring and dissolving, wherein the mass ratio of the chromium nitrate nonahydrate to the terephthalic acid to the ultrapure water to the hydrofluoric acid aqueous solution is (80-90): (30-40): 1 (10-20);
S2, reacting the mixture prepared in the step S1 in a solvothermal reaction kettle at 210-230 ℃ for 7-9 hours, and washing the prepared mixture with DMF and hot ethanol;
S3, soaking the sample in the step S2 in absolute ethyl alcohol for 18-22 hours, washing and drying after the reaction is finished, putting the sample into an ammonium fluoride solution for reacting for 9-11 hours at 58-62 ℃, washing with warm deionized water, and drying overnight at 90-110 ℃ in vacuum to obtain the purified Cr-MOF;
s4, dissolving the purified Cr-MOF in absolute ethyl alcohol, continuously adding ethylenediamine, transferring into a reaction kettle for reaction, washing with ethanol for multiple times after the reaction is finished, and vacuum drying at 90-110 ℃ for 10-14h to obtain the modified Cr-MOF.
2. The method for analysis of modified Cr-MOF-based detection chemicals according to claim 1, wherein: in step 1), the buffer solution is an acidic aqueous solution.
3. The method for analysis of modified Cr-MOF-based detection chemicals according to claim 1, wherein: the pH value of the buffer solution is 3-5.
4. The method for analysis of modified Cr-MOF assay chemistry according to claim 1, wherein: the eluting solution in the step 2) is methanol solution, methanol solution of ammonia water with the volume ratio of 2%, acetonitrile or acetone.
5. The method for analysis of modified Cr-MOF assay chemistry according to claim 1, wherein: the complex solution in the step 2) is acetonitrile water solution;
The volume ratio of acetonitrile to water in the acetonitrile aqueous solution is 1:4.
6. The method for analysis of modified Cr-MOF assay chemistry according to claim 1, wherein: the detection conditions of the high performance liquid chromatography in the step 2) are as follows: a column of waters ACQUity UPLC C18 mm.times.2.1 mm,1.7um was used; the detector is a diode array ultraviolet detector, and the measuring wavelength is 250nm; sample injection amount of the automatic sample injector: 20uL; the mobile phase A is: 975ml of ultrapure water +25ml of 2M ammonium acetate solution +1ml of formic acid +1ml of triethylamine, mobile phase B being acetonitrile.
7. The method for analysis of modified Cr-MOF assay chemistry according to claim 1, wherein: the chemicals comprise psychotropic drugs and metabolites thereof, wherein the psychotropic drugs are risperidone, quetiapine, N-dealkylquetiapine, dehydroaripiprazole and aripiprazole, and the metabolites are 9-hydroxyrisperidone.
8. The method for analysis of modified Cr-MOF assay chemistry according to claim 1, wherein: in step S4, the reaction is shifted the reaction conditions in the kettle are as follows: reacting for 10-14h at 85-95 ℃.
9. The method for analysis of modified Cr-MOF assay chemistry according to claim 1, wherein: the mass ratio of the purified Cr-MOF to the ethylenediamine in the step S4 is 50:1-2.
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