CN113063884A - Liquid chromatography column composite packing and application thereof - Google Patents
Liquid chromatography column composite packing and application thereof Download PDFInfo
- Publication number
- CN113063884A CN113063884A CN202110353538.0A CN202110353538A CN113063884A CN 113063884 A CN113063884 A CN 113063884A CN 202110353538 A CN202110353538 A CN 202110353538A CN 113063884 A CN113063884 A CN 113063884A
- Authority
- CN
- China
- Prior art keywords
- naloxone
- bonded silica
- filler
- silica gel
- liquid chromatography
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002131 composite material Substances 0.000 title claims abstract description 23
- 238000004811 liquid chromatography Methods 0.000 title claims abstract description 16
- 238000012856 packing Methods 0.000 title claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 98
- 229960004127 naloxone Drugs 0.000 claims abstract description 43
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 claims abstract description 41
- 239000000945 filler Substances 0.000 claims abstract description 39
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 22
- 230000002378 acidificating effect Effects 0.000 claims abstract description 11
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 239000007788 liquid Substances 0.000 claims abstract description 7
- 238000011049 filling Methods 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 238000009210 therapy by ultrasound Methods 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- 239000000741 silica gel Substances 0.000 claims description 26
- 229910002027 silica gel Inorganic materials 0.000 claims description 26
- 150000003376 silicon Chemical class 0.000 claims description 25
- 238000005406 washing Methods 0.000 claims description 19
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 13
- 238000010438 heat treatment Methods 0.000 claims description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 claims description 12
- 229960001701 chloroform Drugs 0.000 claims description 11
- 238000010992 reflux Methods 0.000 claims description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 10
- 239000002245 particle Substances 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 8
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 7
- 229910052710 silicon Inorganic materials 0.000 claims description 7
- 239000010703 silicon Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 2
- 239000002114 nanocomposite Substances 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000012863 analytical testing Methods 0.000 claims 1
- 238000004587 chromatography analysis Methods 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 17
- 238000001514 detection method Methods 0.000 abstract description 9
- 238000005220 pharmaceutical analysis Methods 0.000 abstract description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 36
- PWATWSYOIIXYMA-UHFFFAOYSA-N Pentylbenzene Chemical compound CCCCCC1=CC=CC=C1 PWATWSYOIIXYMA-UHFFFAOYSA-N 0.000 description 22
- 238000004458 analytical method Methods 0.000 description 21
- 230000000052 comparative effect Effects 0.000 description 14
- 235000015165 citric acid Nutrition 0.000 description 12
- XVPBINOPNYFXID-JARXUMMXSA-N 85u4c366qs Chemical compound C([C@@H]1CCC[N@+]2(CCC[C@H]3[C@@H]21)[O-])N1[C@@H]3CCCC1=O XVPBINOPNYFXID-JARXUMMXSA-N 0.000 description 11
- ZSBXGIUJOOQZMP-UHFFFAOYSA-N Isomatrine Natural products C1CCC2CN3C(=O)CCCC3C3C2N1CCC3 ZSBXGIUJOOQZMP-UHFFFAOYSA-N 0.000 description 11
- ZSBXGIUJOOQZMP-JLNYLFASSA-N Matrine Chemical compound C1CC[C@H]2CN3C(=O)CCC[C@@H]3[C@@H]3[C@H]2N1CCC3 ZSBXGIUJOOQZMP-JLNYLFASSA-N 0.000 description 11
- 229930014456 matrine Natural products 0.000 description 11
- 229930015582 oxymatrine Natural products 0.000 description 11
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 230000010354 integration Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 235000010724 Wisteria floribunda Nutrition 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000003513 alkali Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 229910021642 ultra pure water Inorganic materials 0.000 description 3
- 239000012498 ultrapure water Substances 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000148 multi-dimensional chromatography Methods 0.000 description 2
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 description 2
- CWVRJTMFETXNAD-BMNNCGMMSA-N (1s,3r,4s,5r)-3-[(e)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy-1,4,5-trihydroxycyclohexane-1-carboxylic acid Chemical compound O[C@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-BMNNCGMMSA-N 0.000 description 1
- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 description 1
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 description 1
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
- 244000061520 Angelica archangelica Species 0.000 description 1
- 241000205585 Aquilegia canadensis Species 0.000 description 1
- 235000007106 Crataegus suborbiculata Nutrition 0.000 description 1
- 241000073432 Crataegus suborbiculata Species 0.000 description 1
- 235000001287 Guettarda speciosa Nutrition 0.000 description 1
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 235000013202 a hawthorn Nutrition 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000004883 caffeic acid Nutrition 0.000 description 1
- 229940074360 caffeic acid Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000001368 chlorogenic acid Nutrition 0.000 description 1
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 description 1
- 229940074393 chlorogenic acid Drugs 0.000 description 1
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 description 1
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 1
- QAIPRVGONGVQAS-UHFFFAOYSA-N cis-caffeic acid Natural products OC(=O)C=CC1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000001785 ferulic acid Nutrition 0.000 description 1
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 1
- 229940114124 ferulic acid Drugs 0.000 description 1
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- KRZBCHWVBQOTNZ-DLDRDHNVSA-N isochlorogenic acid Natural products O[C@@H]1[C@H](C[C@@](O)(C[C@H]1OC(=O)C=Cc2ccc(O)c(O)c2)C(=O)O)OC(=O)C=Cc3ccc(O)c(O)c3 KRZBCHWVBQOTNZ-DLDRDHNVSA-N 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Images
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
- G01N30/60—Construction of the column
- G01N30/6052—Construction of the column body
-
- 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
Landscapes
- 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)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention relates to the technical field of pharmaceutical analysis, in particular to a liquid chromatography column composite filler. The composite filler comprises an octadecylsilane chemically bonded silica filler and a naloxone chemically bonded silica filler, wherein the mass ratio of the octadecylsilane chemically bonded silica to the naloxone chemically bonded silica filler is 1:2-3, and the preparation method of the chromatographic column comprises the steps of mixing the octadecylsilane chemically bonded silica and the naloxone chemically bonded silica in an organic solvent, performing ultrasonic treatment, and filling the mixture into a liquid chromatographic column. The prepared chromatographic column can simultaneously separate and detect hydrophilic components such as acidic components and alkaline components and lipophilic components, and has the advantages of good separation degree, high column efficiency and short detection time.
Description
Technical Field
The invention relates to the technical field of pharmaceutical analysis, in particular to a liquid chromatography column composite filler and a preparation method thereof.
Background
The high performance liquid chromatography is one of the separation and analysis technologies which are developed fastest and applied most widely at present, and plays an increasingly important role in the fields of medicine analysis, life science, environmental monitoring and the like. The performance of chromatographic packing, which is one of the cores separated by liquid chromatography, directly affects the final result of the separation analysis. However, in the case of a complicated sample, particularly, a single column containing a hydrophilic component, a nonpolar component and an acidic component at the same time, it is difficult to satisfy the requirements for separation and column applicability.
Most of the traditional Chinese medicine extractions adopt water as a solvent, the extract contains a large amount of hydrophilic components, wherein no part of the hydrophilic components contains components with strong acidity, such as a hawthorn extracting solution contains a large amount of acidic components such as citric acid, malic acid and flavonoids, a honeysuckle extracting solution contains main active components such as chlorogenic acid, isochlorogenic acid and caffeic acid, and an angelica extracting solution contains acidic components such as succinic acid, ferulic acid and leucovorin. Therefore, the chromatographic packing which can separate a plurality of components with different properties such as hydrophilicity, lipophilicity, acidity, alkalinity and the like in the same chromatographic column is developed, and has potential social value.
Although the multidimensional chromatography technology can meet the requirements of people on resolution, the multidimensional chromatography system has the problems of complex operation, expensive equipment, poor mobile phase compatibility and the like, cannot meet the requirements of analysis and detection of small and medium-sized enterprises, and is difficult to popularize.
The Chinese patent CN101721980B discloses a liquid chromatographic column mixed packing and a chromatographic column, which comprises long-chain alkyl dimethylsilane bonded silica gel and amidosilane bonded silica gel, the weight ratio of the long-chain alkyl dimethylsilane bonded silica gel to the amidosilane bonded silica gel is 10:1-1:10, the average particle size difference is within +/-20 percent, the specific gravity difference is within +/-20 percent, the liquid chromatographic column mixed packing is applied to chromatographic separation under the condition of mixed mobile phase containing acetonitrile and aqueous solution, and the separation application is the chromatographic separation and detection of samples containing compounds with strong hydrophilicity and compounds with strong lipophilicity. However, this chromatographic packing is not ideal in the effect of separating acidic and basic components and cannot separate highly acidic components.
Chinese patent CN209416990U discloses a composite chromatographic column, which comprises a column body, wherein the column body is divided into an upper section and a lower section, the filler used in the upper section is a filler with a naphthyl group bonded on the surface of a microsphere, and the filler used in the lower section is a filler with a benzenesulfonic group bonded on the surface of the microsphere. The composite chromatographic column has good analysis effect. The utility model also discloses a two-dimentional liquid chromatography system, with compound chromatographic column still includes the extraction column in addition as the analytical column, the filler of extraction column has bonded carboxylic group's filler for the microballon surface. The composite liquid chromatography system can realize the simultaneous separation of four psychotropic drugs. The chromatographic column mainly has good separation effect on aromatic compounds and poor separation effect on other alkane nonpolar components.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the liquid chromatographic column composite filler which is simple to prepare, can simultaneously separate various components with different properties such as hydrophilicity, lipophilicity, acidity, alkalinity and the like, and has the advantages of good separation degree, high column efficiency, short separation time and strong acid and alkali resistance.
The purpose of the invention is realized by the following technical scheme:
the composite filler for the liquid chromatography column comprises an octadecylsilane chemically bonded silica filler and a naloxone chemically bonded silica filler.
Preferably, the mass ratio of the octadecylsilane chemically bonded silica filler to the naloxone chemically bonded silica filler is 1: 2-3.
Preferably, the particle size of the octadecylsilane bonded silica filler and naloxone bonded silica filler is 3 to 5 μm.
Preferably, the preparation method of the naloxone-bonded silica gel filler comprises the following steps:
(1) activating the silicon spheres to obtain activated silicon spheres;
(2) then reacting triethoxysilane to the surface of the activated silicon spheres to form a silicon-hydrogen bond, thereby obtaining modified silica gel;
(3) adding naloxone into the modified silica gel, adding an organic solvent and an isopropanol solution of chloroplatinic acid, stirring, heating and refluxing for 8-10h, washing and drying to obtain the nano-composite material.
More preferably, the step (1) operation comprises: the operation of the step (1) comprises the following steps: adding the silicon spheres into hydrochloric acid, reacting for 2-3h, and drying to obtain activated silicon spheres for later use.
Preferably, the reaction in the step (2) is to sequentially add dioxane, 2mol/L hydrochloric acid and 1mol/L triethoxysilane into the activated silicon spheres, heat reflux for 12-15h, wash with 30% acetone water solution and dioxane, and dry to obtain the product; preferably, the mass molar ratio of the activated silicon spheres to the triethoxysilane in the reaction is 1: 0.005-0.006 g/mol; the mass-volume ratio of the activated silica gel to the dioxane added in the reaction is 1: 23-25 g/ml; the drying temperature is 110-130 ℃.
Preferably, the mass molar ratio of the modified silica gel to the naloxone in the step (3) is 1: 5-8g/mol, wherein the organic solvent is chloroform, and the molar ratio of chloroplatinic acid to naloxone is 10-6-10-5: 1; the mass volume ratio of the modified silica gel to the trichloromethane is 1: 25-45 g/mL.
Preferably, the washing in step (3) is washing with acetone and dichloromethane in sequence, and then washing with dichloromethane and acetone in sequence.
Wherein the structural formula of naloxone is:
the silicon-hydrogen bond of the modified silica gel in the step (3) and the olefin bond of the naloxone are subjected to addition reaction under the conditions, and the naloxone molecule is bonded to the modified silica gel; through a great deal of research, the naloxone bonded silica gel is found to have good separation of nonpolar and polar components and good acid resistance of the filler from a plurality of compounds.
The invention also aims to provide a chromatographic column prepared by the composite filler, and the preparation method of the chromatographic column comprises the steps of mixing octadecylsilane chemically bonded silica and naloxone chemically bonded silica in an organic solvent, performing ultrasonic treatment, and filling the mixture into a liquid chromatographic column;
preferably, the organic solvent is one or more of acetone, tetrahydrofuran, polyethylene glycol and carbon tetrachloride; the ultrasonic power is 200-500W, and the ultrasonic time is 20-40 min.
It is still another object of the present invention to provide the use of the above chromatographic packing/chromatographic column composite packing in analytical detection of compositions containing both hydrophilic, lipophilic and acidic and basic components.
The invention has the beneficial effects that:
the chromatographic column prepared by the invention can simultaneously separate and detect hydrophilic, acidic and weak polar components, and has the advantages of good separation degree, high column efficiency and short detection time. Compared with the traditional detection and analysis method adopting a plurality of chromatographic columns, the method is simple and efficient, and can save a large amount of organic reagents and analysis time.
According to a great deal of research, the prepared naloxone bonded silica gel is excellent in acid and alkali resistance, contains groups with good hydrophilicity such as phenolic hydroxyl group, alcoholic hydroxyl group and ether group in naloxone, and can be separated well at the pH of 1-10 through organic compatibility with other non-polar groups and octadecyl bonded silica gel filler. The chromatographic column obtained by mixing the compound with octadecyl bonded silica gel in a specific ratio can well separate polar and nonpolar components, has good peak shape, no tailing and high column efficiency in the analysis of acidic and basic components, well solves the problem that multiple properties of medicinal components in the compound composition need multiple chromatographic columns for analysis and detection, and has the advantages of short time consumption, strong acid and alkali resistance and sensitive analysis.
Drawings
FIG. 1-1 is a chromatogram obtained by analysis using the column prepared in example 1, wherein 1 is citric acid, 2 is oxymatrine, 3 is matrine, and 4 is pentylbenzene;
fig. 1-2 is an enlarged view of a part of a chromatogram obtained by column analysis using the method prepared in example 1, wherein 1 is citric acid, 2 is oxymatrine, 3 is matrine, and 4 is pentylbenzene;
FIG. 2-1 is a chromatogram obtained by analysis using the column prepared in example 2, wherein 1 is citric acid, 2 is oxymatrine, 3 is matrine, and 4 is pentylbenzene;
FIG. 2-2 is an enlarged view of a part of a chromatogram obtained by column analysis using the method prepared in example 2, wherein 1 is citric acid, 2 is oxymatrine, 3 is matrine, and 4 is pentylbenzene;
FIG. 3-1 is a chromatogram obtained by analysis using the column prepared in example 3, wherein 1 is citric acid, 2 is matrine, 3 is oxymatrine, and 4 is pentylbenzene;
FIG. 3-2 is an enlarged view of a part of a chromatogram obtained by column analysis using the method prepared in example 3, wherein 1 is citric acid, 2 is matrine, 3 is oxymatrine, and 4 is pentylbenzene;
FIG. 4-1 is a chromatogram obtained by analysis using the column prepared in comparative example 1, where 1 is citric acid, 2 is pentylbenzene, 3 is matrine, and 4 is oxymatrine;
FIG. 4-2 is an enlarged view of a part of a chromatogram obtained by column analysis using the method of comparative example 1, wherein 1 is citric acid, 2 is pentylbenzene, 3 is matrine, and 4 is oxymatrine;
FIG. 5 is a chromatogram obtained by analysis using the column prepared in comparative example 2, wherein 1 is citric acid, 2 is oxymatrine, 3 is matrine, and 4 is pentylbenzene;
FIG. 6 is a chromatogram obtained by analysis using the column prepared in comparative example 3, wherein 1 is citric acid, 2 is oxymatrine, 3 is matrine, and 4 is pentylbenzene.
Detailed Description
The technical solution of the present invention is further illustrated by the following examples.
Example 1
(1) Adding 25 parts of 1mol/L hydrochloric acid into 1 part of silicon spheres (with an average particle size of 5 μm, Fuji, Japan), stirring at 90 deg.C for reaction for 2h, filtering, washing with ultrapure water to neutrality, and vacuum drying at 120 deg.C to obtain activated silicon spheres;
(2) adding dioxane into the activated silicon spheres (the mass-volume ratio of the activated silicon spheres to the added dioxane is 1: 23g/ml), slowly dropwise adding 2mol/L HC L, heating to 80 ℃, then slowly dropwise adding 1mol/L dioxane solution of triethoxysilane, heating and refluxing for 12h, after the system is drained, washing with 30% acetone aqueous solution and dioxane, and drying at 120 ℃ to obtain modified silicon spheres, wherein the mass-mole ratio of the activated silicon spheres to the triethoxysilane is 1: 0.006 g/mol.
(3) And sequentially adding trichloromethane, naloxone and 2% isopropanol solution of chloroplatinic acid into the modified silica gel, magnetically stirring, heating and refluxing for 8h, filtering, sequentially washing a filter cake with acetone and dichloromethane, sequentially washing with dichloromethane and acetone, and drying at 110 ℃ to obtain the naloxone bonded silica gel. Wherein the mass molar ratio of the modified silica gel to the naloxone is 1: 5g/mol of chloroplatinic acid with naloxone as reaction substrateThe molar ratio is 10-6: 1; the mass volume ratio of the modified silica gel to the trichloromethane is 1: 25 g/mL;
(4) and (3) carrying out ultrasonic treatment on 1 part of octadecyl bonded silica gel and 2.5 parts of naloxone bonded silica gel prepared in the step (2) in 150 parts of carbon tetrachloride solvent at 200W for 40min to prepare a mixed solution, and filling the mixed solution into a chromatographic column with the size of 4.6mm multiplied by 150 mm.
The octadecyl bonded silica gel is purchased from New Material Co, Ltd, of the family Rigaceae, and is named Fuji Chromatorex filler, the product number is 112926-00-8, and the particle size is 3 μm.
Example 2
(1) Adding 25 parts of 1mol/L hydrochloric acid into 1 part of silicon spheres (with an average particle size of 5 μm, Fuji, Japan), stirring at 90 deg.C for reaction for 2h, filtering, washing with ultrapure water to neutrality, and vacuum drying at 120 deg.C to obtain activated silicon spheres;
(2) adding dioxane into the activated silicon spheres (the mass volume ratio of the activated silicon spheres to the added dioxane is 1: 25g/ml), slowly dropwise adding 2mol/L HC L, heating to 80 ℃, then slowly dropwise adding 1mol/L dioxane solution of triethoxysilane, heating and refluxing for 15h, filtering, washing a filter cake with 30% acetone aqueous solution and dioxane, and drying at 130 ℃ to obtain modified silicon spheres, wherein the mass mole ratio of the activated silicon spheres to the triethoxysilane is 1: 0.005 g/mol.
(3) And sequentially adding trichloromethane, naloxone and 2% isopropanol solution of chloroplatinic acid into the modified silica gel, magnetically stirring, heating and refluxing for 10h, filtering, sequentially washing a filter cake with water, acetone and dichloromethane, sequentially washing with dichloromethane and acetone, and drying at 110 ℃ to obtain the naloxone dimethylsilane bonded silica gel. Wherein the mass molar ratio of the modified silica gel to the naloxone is 1: 5g/mol, the molar ratio of chloroplatinic acid to naloxone as a reaction substrate is 10-6: 1; the mass volume ratio of the modified silica gel to the trichloromethane is 1: 45 g/mL;
(4) and (3) carrying out ultrasonic treatment on 1 part of octadecyl bonded silica gel and 3 parts of naloxone bonded silica gel prepared in the step (2) in 150 parts of carbon tetrachloride solvent at 200W for 40min to prepare a mixed solution, and filling the mixed solution into a chromatographic column with the size of 4.6mm multiplied by 150 mm.
The octadecyl bonded silica gel is purchased from New Material Co, Ltd, of the family Rigaceae, and is named Fuji Chromatorex filler, the product number is 112926-00-8, and the particle size is 3 μm.
Example 3
(1) Adding 25 parts of 1mol/L hydrochloric acid into 1 part of silicon spheres (with an average particle size of 5 μm, Fuji, Japan), stirring at 90 deg.C for reaction for 3h, filtering, washing with ultrapure water to neutrality, and vacuum drying at 120 deg.C to obtain activated silicon spheres;
(2) adding dioxane into the activated silicon spheres (the mass volume ratio of the activated silicon spheres to the added dioxane is 1: 25g/ml), slowly dropwise adding 2mol/L HC L, heating to 80 ℃, then slowly dropwise adding 1mol/L dioxane solution of triethoxysilane, heating and refluxing for 12h, filtering, washing a filter cake with 30% acetone aqueous solution and dioxane, and drying at 130 ℃ to obtain modified silicon spheres, wherein the mass mole ratio of the activated silicon spheres to the triethoxysilane is 1: 0.006 g/mol.
(3) And sequentially adding trichloromethane, naloxone and 2% isopropanol solution of chloroplatinic acid into the modified silica gel, magnetically stirring, heating and refluxing for 10h, filtering, sequentially washing a filter cake with acetone and dichloromethane, sequentially washing with dichloromethane and acetone, and drying at 130 ℃ to obtain the naloxone dimethylsilane bonded silica gel. Wherein the mass molar ratio of the modified silica gel to the naloxone is 1: 8g/mol, the molar ratio of chloroplatinic acid to naloxone as a reaction substrate is 10-5: 1; the mass volume ratio of the modified silica gel to the trichloromethane is 1: 35 g/mL;
(4) and (3) carrying out ultrasonic treatment on 1 part of octadecyl bonded silica gel and 2 parts of naloxone bonded silica gel prepared in the step (2) in 150 parts of carbon tetrachloride solvent at 200W for 40min to prepare a mixed solution, and filling the mixed solution into a chromatographic column with the size of 4.6mm multiplied by 150 mm.
The octadecyl bonded silica gel is purchased from New Material Co, Ltd, of the family Rigaceae, and is named Fuji Chromatorex filler, the product number is 112926-00-8, and the particle size is 5 μm.
Comparative example 1
The comparative example differs from example 3 in that 1 part by mass of naloxone-bonded silica gel was added, and the remainder was identical to example 3.
Comparative example 2
The difference between the comparative example and the example 3 is that toluene is used as the organic solvent in the step (3), and the heating reflux time is 11h, and the rest is consistent with the example 3.
Comparative example 3
The comparative example is different from example 3 in that the mass molar ratio of the modified silica gel to naloxone in step (3) is 1: 3g/mo L, the rest remaining in accordance with example 3.
Effect example 1
The columns obtained in examples 1 to 3 and comparative examples 1 to 3 were used, and the test sample was a 70% acetonitrile aqueous solution containing citric acid, matrine, oxymatrine and pentylbenzene, and the detection wavelength was 210nm as determined by analysis on a waters e2690-UV high performance liquid chromatograph at a flow rate of 1ml/min and a column temperature of 25 ℃ wherein the column of example 3 was passed through the column with a 2% trifluoroacetic acid solution for one week before injection, and then the column was washed with water and acetonitrile-water (70:30) in this order.
The spectra obtained in the above experiment are shown in FIGS. 1-1 to 6, and the integration results are shown in the following tables 1-6.
Table 1 example 1 table of chromatographic integration results
Table 2 example 2 table of chromatographic integration results
Table 3 example 3 table of chromatographic integration results
Table 4 table of chromatographic integration results of comparative example 1
TABLE 5 TABLE OF COMPARATIVE EXAMPLE 2 CHROMATOGRAPHIC INTEGRATION RESULTS
Table 6 table of chromatographic integration results of comparative example 3
The result shows that when the mixing ratio of the octadecyl bonded silica gel to the naloxone bonded silica gel is 1:2-3, the separation degree is good when acidic, alkaline and nonpolar components are separated, the column efficiency is high, the detection time is short, and the acid resistance of the chromatographic packing is strong. When the proportion of the naloxone bonded silica gel in the composite filler is reduced, the separation effect of four components with different polarities and acid and alkali components is poor, and the separation degree does not meet the content measurement requirement; in the research of the reaction of naloxone and modified silica gel, the invention discovers that the selection of an organic solvent and the reaction time have certain influence on the final separation effect of the naloxone and the modified silica gel, the recovery of the product in a column is influenced to a certain extent, the initial judgment shows that the boiling points of toluene and trichloromethane have certain difference, and the difference of the reaction temperature has certain influence on the yield; the invention also finds that the mass molar ratio of reaction substrates hydrogenated silica gel and naloxone is 1: 5-8g/moL, the chromatographic column has good separation effect.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and decorations can be made without departing from the concept of the present invention, and these modifications and decorations should also be regarded as being within the protection scope of the present invention.
Claims (10)
1. The liquid chromatography column composite filler is characterized by comprising octadecylsilane chemically bonded silica filler and naloxone chemically bonded silica filler.
2. The liquid chromatography column composite filler of claim 1, wherein the mass ratio of octadecylsilane chemically bonded silica filler to naloxone-bonded silica filler is 1: 2-3.
3. The composite filler for liquid chromatography columns according to claim 1, characterized in that the particle size of the octadecylsilane bonded silica filler and naloxone bonded silica filler is 3-5 μm.
4. The composite packing for a liquid chromatography column according to claim 1, wherein the preparation method of the naloxone-bonded silica gel packing comprises the following steps:
(1) activating the silicon spheres to obtain activated silicon spheres;
(2) then reacting triethoxysilane to the surface of the activated silicon spheres to form a silicon-hydrogen bond, thereby obtaining modified silica gel;
(3) adding naloxone into the modified silica gel, adding an organic solvent and an isopropanol solution of chloroplatinic acid, stirring, heating and refluxing for 8-10h, washing and drying to obtain the nano-composite material.
5. The composite packing for liquid chromatography columns of claim 4, wherein step (1) operation comprises: adding the silicon spheres into hydrochloric acid, reacting for 2-3h, and drying to obtain activated silicon spheres for later use.
6. The composite filler for the liquid chromatography column as claimed in claim 4, wherein the reaction in step (2) is obtained by sequentially adding dioxane, 2mol/L hydrochloric acid and 1mol/L triethoxysilane into an activated silicon ball, heating and refluxing for 12-15h, washing with 30% acetone aqueous solution and dioxane, and drying; preferably, the mass molar ratio of the activated silicon spheres to the triethoxysilane in the reaction is 1: 0.005-0.006 g/mol; the mass-volume ratio of the activated silica gel to the dioxane added in the reaction is 1: 23-25 g/ml; the drying temperature is 110-130 ℃.
7. The composite packing for liquid chromatography columns according to claim 4, characterized in that the mass molar ratio of the modified silica gel and naloxone in step (3) is 1: 5-8g/mol, the organic solvent is trichloromethane, and the mol ratio of the chloroplatinic acid to the naloxone is 10-6-10-5: 1; the mass volume ratio of the modified silica gel to the trichloromethane is 1: 25-45 g/mL.
8. The composite packing for liquid chromatography columns according to claim 4, characterized in that the washing in step (3) is acetone and dichloromethane sequentially, and then dichloromethane and acetone sequentially.
9. A chromatographic column made of the composite filler according to any one of claims 1 to 8, wherein the preparation method of the chromatographic column comprises the steps of placing the octadecylsilane chemically bonded silica and the naloxone chemically bonded silica in an organic solvent, mixing, performing ultrasonic treatment, and filling the mixture into a liquid chromatographic column; preferably, the organic solvent is one of acetone, tetrahydrofuran and carbon tetrachloride; the ultrasonic power is 200-500W, and the ultrasonic time is 30-50 min.
10. Use of a composite packing for chromatography columns according to any of claims 1-8 for analytical testing of products containing both hydrophilic, lipophilic and acidic and basic components.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110353538.0A CN113063884B (en) | 2021-03-31 | 2021-03-31 | Liquid chromatography column composite packing and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110353538.0A CN113063884B (en) | 2021-03-31 | 2021-03-31 | Liquid chromatography column composite packing and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113063884A true CN113063884A (en) | 2021-07-02 |
| CN113063884B CN113063884B (en) | 2021-11-16 |
Family
ID=76565252
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110353538.0A Active CN113063884B (en) | 2021-03-31 | 2021-03-31 | Liquid chromatography column composite packing and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113063884B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721980A (en) * | 2009-11-13 | 2010-06-09 | 天津博纳艾杰尔科技有限公司 | Mixed fillers of liquid-phase chromatographic column and chromatographic column |
| CN103028383A (en) * | 2012-12-31 | 2013-04-10 | 浙江月旭材料科技有限公司 | Silica gel chromatography packing and preparation method thereof |
| CN104558255A (en) * | 2015-01-30 | 2015-04-29 | 北京理工大学 | Cyclodextrin derivative containing oxazoline segments as well as preparation and application of hydrogenated silica gel stationary phase bonded with cyclodextrin derivative |
| CN104768536A (en) * | 2012-09-17 | 2015-07-08 | 格雷斯公司 | Functionalized particulate support material and methods of making and using the same |
| CN111329845A (en) * | 2020-04-08 | 2020-06-26 | 江苏长泰药业有限公司 | Preparation process for improving naltrexone microsphere encapsulation rate |
-
2021
- 2021-03-31 CN CN202110353538.0A patent/CN113063884B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721980A (en) * | 2009-11-13 | 2010-06-09 | 天津博纳艾杰尔科技有限公司 | Mixed fillers of liquid-phase chromatographic column and chromatographic column |
| CN104768536A (en) * | 2012-09-17 | 2015-07-08 | 格雷斯公司 | Functionalized particulate support material and methods of making and using the same |
| CN103028383A (en) * | 2012-12-31 | 2013-04-10 | 浙江月旭材料科技有限公司 | Silica gel chromatography packing and preparation method thereof |
| CN104558255A (en) * | 2015-01-30 | 2015-04-29 | 北京理工大学 | Cyclodextrin derivative containing oxazoline segments as well as preparation and application of hydrogenated silica gel stationary phase bonded with cyclodextrin derivative |
| CN111329845A (en) * | 2020-04-08 | 2020-06-26 | 江苏长泰药业有限公司 | Preparation process for improving naltrexone microsphere encapsulation rate |
Non-Patent Citations (3)
| Title |
|---|
| A BACHRACH ET AL.: "ATTACHMENT OF DRUGS TO POLYDIMETHYLSILOXANES", 《EUR. POLYM.J.》 * |
| BL GE ET AL.: "Synthesis of a naloxone affinity column and its use to isolate opiate binding sites from neuroblastoma X glioma NG108-15 hybrid cells", 《PROCEEDINGS OF THE WESTERN PHARMACOLOGY SOCIETY》 * |
| 于世林: "《高效液相色谱方法及应用》", 31 January 2000, 化学工业出版社 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113063884B (en) | 2021-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102489275B (en) | Phenylalanine-substituted calix [4] arene bonded silica gel stationary phase, preparation method thereof, and application thereof | |
| CN105498694B (en) | The metallic organic framework magnetic material of a kind of temperature sensitive polymer parcel and application thereof | |
| CN103028383B (en) | Silica gel chromatography packing and preparation method thereof | |
| CN103399099B (en) | Method for detecting nine organophosphorus pesticides simultaneously | |
| CN103551118B (en) | Column [5] aromatic bonding silica gel stationary phase as well as preparation method and application thereof | |
| CN102133256A (en) | Rhodiola crenulata extract and preparation method thereof | |
| CN105111255A (en) | Extraction and separation method for echinacoside and verbascoside in cistanche | |
| CN101775152B (en) | Preparation method of surface imprinted material for matrine substance separation and purification | |
| CN103007905A (en) | Tetraazacalix [2] arene [2] triazine bonded silica gel solid phase extraction material, preparation method and application thereof | |
| CN102775554B (en) | Preparation method for cinnamaldehyde surface molecularly imprinted polymer | |
| US9453041B2 (en) | Method for preparing albiflorin and paeoniflorin | |
| CN101721516B (en) | Preparation method of gardenia extract | |
| CN102489274A (en) | Alanine substituted calix[4]arene bonded silica stationary phase and preparation method and application thereof | |
| CN113063884B (en) | Liquid chromatography column composite packing and application thereof | |
| CN1869055A (en) | Method of extracting and separating ginseng saponine monomer from ginseng leaf | |
| CN101050227A (en) | Technique for extracting compound of flavone in high purity from whole individual plant of tartary buckwheat through method of adsorptive resin | |
| CN103551125A (en) | Preparation method of Sudan red II molecular imprinting solid-phase extraction column filling material | |
| CN109265494B (en) | Method for extracting kaempferol glucoside compounds from camellia reticulata | |
| CN105709708B (en) | A kind of proline derivatization cup [4] aromatic hydrocarbons bonded silica gel stationary phase and preparation method and application | |
| CN1283636C (en) | Separation purification method of catechin monomer | |
| CN102507820B (en) | Method for detecting trichlorfon and monocrotophos | |
| CN101220036B (en) | Extraction of active ingredient such as betulinic acid from common camptotheca fruit with clean method | |
| CN104262076B (en) | A kind of method utilizing Silver Nitrate silica gel chromatography purification plant origin squalene | |
| CN102698722A (en) | Method for preparing bisphenol A molecularly imprinted polymer solid phase extraction column | |
| CN102174138B (en) | Preparation method and application of codonopsis lactone molecularly imprinted solid phase extraction column |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |