CN105424838A - Method for detecting synthetic musk - Google Patents
Method for detecting synthetic musk Download PDFInfo
- Publication number
- CN105424838A CN105424838A CN201510910207.7A CN201510910207A CN105424838A CN 105424838 A CN105424838 A CN 105424838A CN 201510910207 A CN201510910207 A CN 201510910207A CN 105424838 A CN105424838 A CN 105424838A
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- CN
- China
- Prior art keywords
- muscone
- muskone
- musk
- medicinal material
- control medicinal
- 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
- 241000402754 Erythranthe moschata Species 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 title claims abstract description 21
- ALHUZKCOMYUFRB-UHFFFAOYSA-N muskone Natural products CC1CCCCCCCCCCCCC(=O)C1 ALHUZKCOMYUFRB-UHFFFAOYSA-N 0.000 claims abstract description 127
- ALHUZKCOMYUFRB-OAHLLOKOSA-N Muscone Chemical compound C[C@@H]1CCCCCCCCCCCCC(=O)C1 ALHUZKCOMYUFRB-OAHLLOKOSA-N 0.000 claims abstract description 80
- 239000003814 drug Substances 0.000 claims abstract description 41
- 150000002596 lactones Chemical class 0.000 claims abstract description 38
- UZPGQSNVEPBXNO-UHFFFAOYSA-N 4-methylcyclopentadecan-1-one Chemical compound CC1CCCCCCCCCCCC(=O)CC1 UZPGQSNVEPBXNO-UHFFFAOYSA-N 0.000 claims abstract description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- 238000001514 detection method Methods 0.000 claims description 32
- 239000000463 material Substances 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 25
- 239000013558 reference substance Substances 0.000 claims description 24
- 229940079593 drug Drugs 0.000 claims description 23
- 238000012360 testing method Methods 0.000 claims description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- 238000006356 dehydrogenation reaction Methods 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 11
- 230000014759 maintenance of location Effects 0.000 claims description 9
- 239000007789 gas Substances 0.000 claims description 8
- 239000012467 final product Substances 0.000 claims description 7
- 238000004817 gas chromatography Methods 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- -1 filter Substances 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 238000010521 absorption reaction Methods 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000243 solution Substances 0.000 description 27
- 239000004519 grease Substances 0.000 description 26
- 239000000523 sample Substances 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 239000006187 pill Substances 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 239000012085 test solution Substances 0.000 description 8
- HORQAOAYAYGIBM-UHFFFAOYSA-N 2,4-dinitrophenylhydrazine Chemical compound NNC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O HORQAOAYAYGIBM-UHFFFAOYSA-N 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 208000019622 heart disease Diseases 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000012797 qualification Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 244000153234 Hibiscus abelmoschus Species 0.000 description 2
- 241001416180 Moschidae Species 0.000 description 2
- SUAUILGSCPYJCS-UHFFFAOYSA-N Musk ambrette Chemical compound COC1=C([N+]([O-])=O)C(C)=C([N+]([O-])=O)C=C1C(C)(C)C SUAUILGSCPYJCS-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000009112 niuhuang Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 235000013599 spices Nutrition 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AQHWOHJRLSNGFD-UHFFFAOYSA-N N-anilino-N-nitronitramide ethanol Chemical compound C(C)O.[N+](=O)([O-])N(NC1=CC=CC=C1)[N+](=O)[O-] AQHWOHJRLSNGFD-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 244000096712 ambrette Species 0.000 description 1
- 235000002783 ambrette Nutrition 0.000 description 1
- 230000003257 anti-anginal effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000005100 correlation spectroscopy Methods 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 239000000341 volatile oil 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
- G01N30/90—Plate chromatography, e.g. thin layer or paper 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/025—Gas chromatography
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)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for detecting synthetic musk. Muscone, 4-methyl-cyclopentadecanon, musk lactone, dehydrogenated musk lactone and C18H2803 of synthetic musk in a medicine are qualitatively detected, so as to judge whether the medical synthetic musk conforming to the regulations of the pharmacopeia is used in the medicine. Through the method, the safety and effectiveness of the medicine can be judged accurately, and the medicine quality is controlled more comprehensively.
Description
Technical field
The present invention relates to muscone and differentiate detection technique field, particularly relate to the detection method of a kind of muscone.
Background technology
Moschus is widely applied in field of medicaments, cosmetics as traditional Chinese medicine material, and after musk deer is listed in National Grade I Protected Wildlife, the natural musk taking from male musk deer only can be used in several herbal species that country specifies.In order to save the wild animals, can meet tcm clinical demand again, now succeed in developing the unique medicinal muscone of China, authentication code is the accurate word Z20040042 of traditional Chinese medicines simultaneously.Prove through the research such as pharmacological effect, clinical testing, muscone's main pharmacological and natural musk are substantially identical, and physical behavior is similar, and clinical efficacy is definite, use safety, can be equal to natural musk to fill a prescription to use.
As can be seen here, muscone is an individual calling, representative be bulk drug through the legal approval of country, other musk ambrette any should by the title titled with " muscone ".Other musk ambrette also claims " synthetic musk " (being different from " muscone ") sometimes, refers to the various single chemical composition with similar muskiness produced by synthesis.Its purposes is generally the fixastive of essence.These musk ambrettes can be divided into by the chemical constitution of synthesis: nitro musk, polycyclic musk, macrocyclic musk.
One of principal ingredient in muscone is muskone (C
16h
30o), chemical name is 3-methylcyclopentadecanone, has volatility, and its structural formula is as follows:
。
Muscone has resuscitation with aromatics, the effect such as network, swelling and pain relieving of stimulating the menstrual flow, energy coronary artery dilator, and Antianginal effect and monobel are similar to.Containing the Chinese patent drug about 300 kinds of muscone, as the Angong Niuhuang Wan, Liushen Pills, bear gall pills for curing heart disease etc. of determined curative effect.
Chinese patent drug prevailing quality detection control point containing " muscone " in prior art is as follows:
Shexiang Fengshi Capsules: [assay item] muscone: chromatographic condition: the capillary column being Stationary liquid with 100% dimethyl polysiloxane (column length 10m, internal diameter 0.32mm, film thickness 0.25um); Column temperature 180 DEG C; Test sample preparation method: get this product 40, accurately weighed content weight, grinds well, gets about 5 grams, accurately weighed, and precision adds absolute ethyl alcohol 25 milliliters, jolting, places 24 hours, shake well, filters, to obtain final product.(with muskone reference substance for contrast)
Bear gall pills for curing heart disease: [discriminating item] gets this product 2.5 grams, porphyrize, adds diethyl ether 20 milliliters, ultrasonic process 10 minutes, filters, filtrate volatilizes, and residue adds 1 milliliter, ethyl acetate, makes dissolving, as need testing solution, point sample, in same silica gel plate, take toluene as developping agent, and DNPH test solution develops the color.(with muskone reference substance for contrast)
Angong Niuhuang Wan: [discriminating item] gets this product 3 grams, shreds, according to the experiment of determination of volatile oil method, add cyclohexane 0.5ml, be slowly heated to boil, keep micro-and boil about 2.5 hours, after placing 30min, getting cyclohexane liquid is need testing solution; With phenyl (50%) methyl silicone (OV-17) for Stationary liquid, coating concentration is 9%, column length 2m; Column temperature 180 DEG C.(with muskone reference substance for contrast)
Above reference mark can not be distinguished the Moschus used in medicine and whether meet medicinal muscone, cannot to distinguish and come, to such an extent as to cannot judge the safety and efficacy of its finished product with other as the synthetic musk that spices uses.Current Shandong Hong Jitang pharmacy Group Plc is unique market supply person of domestic medicinal muscone muskone used, muscone's Chinese patent medicine preparation of commercial type only detects wherein relevant muskone composition, and in fact Shandong Hong Jitang pharmacy Group Plc adopts the accessory substance 4-methylcyclopentadecanone of closed loop legal system standby " muskone " (patent publication No. is method disclosed in the patent of CN1994998A) to be also effective constituent; Only using muskone single component as the detection method of muscone in the detection method of prior art, can not accurately judge Drug safety and validity, more fully can not control drug quality.
Summary of the invention
Object of the present invention is exactly defect for above-mentioned existence and provides the detection method of a kind of muscone.The method, by muscone's related substance composition in detection of drugs, judges that this drug use meets the medicinal muscone of States Pharmacopoeia specifications.Can accurately judge Drug safety and validity by the inventive method, more fully control drug quality.
The detection method technical scheme of a kind of muscone of the present invention is, muskone, the 4-methylcyclopentadecanone of muscone in qualitative detection medicine, and musk lactone, dehydrogenation musk lactone and C
18h
280
3at least one in three kinds of compositions, if containing above composition, then judge that this drug use meets the medicinal muscone of States Pharmacopoeia specifications.
Use muskone, the 4-methylcyclopentadecanone of muscone in gas chromatography qualitative detection medicine, and musk lactone, dehydrogenation musk lactone and C
18h
280
3at least one in three kinds of compositions.
Use muskone, 4-methylcyclopentadecanone, musk lactone, the dehydrogenation musk lactone four kinds of compositions of muscone in gas chromatography qualitative detection medicine, if containing above composition, then judge that this drug use meets the medicinal muscone of States Pharmacopoeia specifications.
Use muskone, 4-methylcyclopentadecanone, musk lactone, dehydrogenation musk lactone, the C of muscone in gas chromatography qualitative detection medicine
18h
280
3five kinds of compositions, if containing above composition, then judge that this drug use meets the medicinal muscone of States Pharmacopoeia specifications.
Use muskone, 4-methylcyclopentadecanone, the musk lactone three kinds of compositions of muscone in gas chromatography qualitative detection medicine, if containing above composition, then judge that this drug use meets the medicinal muscone of States Pharmacopoeia specifications.
Use muskone, 4-methylcyclopentadecanone, the dehydrogenation musk lactone three kinds of compositions of muscone in gas chromatography qualitative detection medicine, if containing above composition, then judge that this drug use meets the medicinal muscone of States Pharmacopoeia specifications.
Use muskone, the 4-methylcyclopentadecanone two kinds of compositions of muscone in gas chromatography qualitative detection medicine, if containing above composition, then judge that this drug use meets the medicinal muscone of States Pharmacopoeia specifications.
The detection method of described a kind of muscone, comprises the following steps:
(1) Chinese patent drug to be measured is prepared into need testing solution by the preparation of need testing solution;
(2) muscone's control medicinal material is made the control medicinal material solution of every 1ml containing muscone 20mg by the preparation of control medicinal material solution;
(3) reference substance solution of every 1ml containing muskone 1mg made by muskone reference substance by the preparation of reference substance solution;
(4) measure accurate absorption control medicinal material solution, reference substance solution and each 1 μ l of need testing solution respectively, inject gas chromatograph measures;
(5) by gas chromatogram, can detect in test sample collection of illustrative plates, with the muskone in muscone's control medicinal material collection of illustrative plates, 4-methylcyclopentadecanone, and musk lactone, dehydrogenation musk lactone and C
18h
280
3there is chromatographic peak in the identical retention time place of at least one in three kinds of compositions, can go out this sample and use the medicinal muscone meeting States Pharmacopoeia specifications by Qualitive test.
In mensuration process, GC conditions is: column temperature is temperature programme, and initial temperature is 140 ± 5 DEG C, keeps 10 ± 2min, then 170 ± 5 DEG C are risen to the speed of 2-3 per minute DEG C, keep 5 ± 2min, injector temperature is 220 ± 5 DEG C, and hydrogen flame ionization detector temperature is 250 DEG C.
Preferably, in mensuration process, GC conditions is: column temperature is temperature programme, and initial temperature is 140 DEG C, keep 10min, then rise to 170 DEG C with the speed of 2 DEG C per minute, keep 5min, injector temperature is 220 DEG C, and hydrogen flame ionization detector temperature is 250 DEG C.
Step (1) is specially: get Chinese patent drug to be measured (honey pill agent shreds, and content got by capsule, tablet, granule, water-bindered pill porphyrize) 5g, accurately weighed, put in tool plug conical flask, add diethyl ether 50ml, weighed weight, water-bath refluxes 30 minutes, lets cool, weighed weight again, supplies the weight of less loss with ether, filter, filtrate water bath method, adds methyl alcohol and dissolves, be settled to 2 milliliters, shake up, to obtain final product.
Step (2) is specially: precision takes muscone's control medicinal material and adds the ultrasonic process of methyl alcohol, and insolubles discards, and shakes up, and filters, and makes the control medicinal material solution of every 1ml containing muscone 20mg.
Step (3) is specially: precision takes muskone reference substance and adds methyl alcohol, shakes up, and filters, and makes the reference substance solution of every 1ml containing muskone 1mg.
Muskone, the 4-methylcyclopentadecanone of muscone in step (5), and musk lactone, dehydrogenation musk lactone and C
18h
280
3at least one chromatographic peak determination methods in three kinds of compositions is:
1. muskone chromatographic peak in muscone's control medicinal material collection of illustrative plates is determined by main peak retention time in muskone reference substance collection of illustrative plates;
2. in muscone's control medicinal material collection of illustrative plates, take muskone as main peak, the peak occurred at its front 1-3 minute is musk lactone chromatographic peak, the peak occurred at 0.5-1.5 minute is thereafter 4-methylcyclopentadecanone chromatographic peak, the peak occurred at 2-4 minute is thereafter dehydrogenation musk lactone chromatographic peak, and the peak occurred at 11.5-12.5 minute is thereafter C
18h
280
3chromatographic peak, determines 4-methylcyclopentadecanone, musk lactone, dehydrogenation musk lactone and C respectively
18h
280
3chromatographic peak retention time, thus provide foundation for Qualitive test sample.
Wherein, test sample collection of illustrative plates, control medicinal material collection of illustrative plates, reference substance collection of illustrative plates should same gas chromatograph within the same day be made.
The detection method beneficial effect of a kind of muscone of the present invention is: the present invention detects Multiple components, can distinguish " synthetic musk as spices uses " and medicinal " muscone " on the market, consider based on security, validity, can differentiate in Chinese patent drug, whether to use muscone to feed intake, significant, drug quality can be controlled more comprehensively.
accompanying drawing illustrates:
Figure 1 shows that the silica gel thin-layer plate spray of the point sample amount 5ul of embodiment 1 containing grease 1,2,3,4 is with DNPH test solution colour developing thin layer plate figure;
Figure 2 shows that the silica gel thin-layer plate spray of the point sample amount 10ul of embodiment 1 containing grease 1,2,3,4 is with DNPH test solution colour developing thin layer plate figure;
Figure 3 shows that embodiment 1 grease 1 mass spectrogram;
Figure 4 shows that embodiment 1 grease 2 mass spectrogram;
Figure 5 shows that embodiment 1 grease 3 mass spectrogram;
Figure 6 shows that embodiment 1 grease 4 high resolution mass spectrum figure;
Figure 7 shows that embodiment 1 grease 4
1hNMR composes;
Figure 8 shows that methanol solvate blank sample chromatogram;
Figure 9 shows that muscone's control medicinal material chromatogram;
Figure 10 shows that muskone reference substance collection of illustrative plates;
Figure 11 shows that muscone's sample chromatogram in embodiment 2 bear gall pills for curing heart disease.
Wherein, 1-musk lactone, 2-dehydrogenation musk lactone, 3-C
18h
280
3, 4-4-methylcyclopentadecanone, 5-muskone.
embodiment:
In order to understand the present invention better, describe technical scheme of the present invention in detail with instantiation below, but the present invention is not limited thereto.
The qualification of related substance
1, related substance preparation
(1) muskone 20 grams that Shandong Hong Jitang pharmacy Group Plc produces is taken, add methyl alcohol (ether or chloroform or acetone or chloroform-methanol any mixture or chloroform-low boiling point solvent such as acetone arbitrary proportion potpourri or methylene chloride) 20-40 milliliters, dissolve, mixing, point sample is (every plate silica G consumption 30 grams) on 40 blocks of 20cm*20cm thin-layer silicon offset plates, after volatilizing solvent, launch in developing tank respectively, developping agent is chloroform-methanol (10:1), silica gel plate dries, dinitrophenylhydrazine ethanol test solution colour developing (silica gel plate developing portions), divide by colour developing speckle displacement and get silica gel on plate, by thin layer plate from bottom to up, by blob classifications, merge, obtain 5 part silicone gel powder and (be powder 1-5, wherein powder 5 is 3-methylcyclopentadecanone).
(2) powder 1, powder 2, powder 3, powder 4 is got respectively, add 2-5 times of methyl alcohol (ether or chloroform or acetone or chloroform-methanol any mixture or chloroform-low boiling point solvent such as acetone arbitrary proportion potpourri or methylene chloride) ultrasonic 20 minutes, filter, filtrate low temperature is concentrated on a small quantity, obtains colourless solution 1-4.
(3) compression leg purifying in: filler C-18(50-80um), get colourless solution 1-4 loading wash-out respectively, filler materials are sample size 20-50 times, and chloroform-methanol (20:1-10:1) gradient elution obtains colorless oil 1-4.
2, related substance qualification:
2.1 related substance thin-layer chromatography qualifications
Get the grease 1,2,3,4 prepared, add methyl alcohol respectively, the solution of configuration concentration 2mg/ml is as need testing solution; Point sample is in same silica gel thin-layer plate, and point sample amount 5ul, using chloroform-methanol volume ratio for 20:1 is as developping agent, launches, spray and develop the color with DNPH test solution.The silica gel thin-layer plate spray obtaining the point sample amount 5ul containing grease 1,2,3,4, with DNPH test solution colour developing thin layer plate figure, as shown in Figure of description Fig. 1, from left to right, is followed successively by grease 4, grease 1, grease 2, grease 3.
Get the grease 1,2,3,4 prepared, add methyl alcohol respectively, the solution of configuration concentration 2mg/ml is as need testing solution; Point sample in same silica gel thin-layer plate, point sample amount 10ul, using sherwood oil (60-90 DEG C)-ethyl acetate volume ratio be 10:1 as developping agent, launch, spray and develop the color with DNPH test solution.Obtain the silica gel thin-layer plate spray of the point sample amount 10ul containing grease 1,2,3,4 with DNPH test solution colour developing thin layer plate figure, as shown in Figure of description Fig. 2.From left to right, grease 1, grease 2, grease 3, grease 4 is followed successively by
After being launched respectively by above 2 thin-layer developing systems, 2 collection of illustrative plates drawn are known, and grease 1-4 is single component.
2.2 related substance mass spectrums, nuclear magnetic resonance etc.
Colorless oil 4: sample has 4 asymmetric carbon atoms, but the optical activity measured in methyl alcohol is 0, and explanation is
d,lthe raceme of-configuration 1:1 geometric ratio mixing.It is consistent that high resolution mass spectrum shows that sample forms with 4-methylcyclopentadecanone element, molecular formula C
16h
30o.Infrared spectrum (IR) shows in sample molecule containing the structure such as carbonyl, methylene.Ultra-violet absorption spectrum (UV) shows in sample molecule containing carbonyl.Proton nmr spectra (
1hNMR), carbon spectrum (
13cNMR, dept) and Correlated Spectroscopy (
1h-
1hCOSY, HSQC, HMBC) confirm C, H ownership meet sample molecule structural formula.The structural formula (4-methylcyclopentadecanone) of final sample is defined as:
。
Employing high resolution mass spectrum is analyzed, and document comparison, determines grease 1,2,3 structure or molecular formula.
Can show that grease 1 is musk lactone eventually through above test, molecular formula is C
16h
280
2; Grease 2 is dehydrogenation musk lactone, and molecular formula is C
18h
260
2; The molecular formula of grease 3 is C
18h
280
3, grease 4 is 4-methylcyclopentadecanone, and molecular formula is C
16h
30o.
Embodiment 1
Muscone's gas chromatographic detection (qualitative detection) in bear gall pills for curing heart disease
Gas chromatographic detection
chromatographic condition and system suitability
Column temperature is temperature programme, and initial temperature is 140 DEG C, keeps 10min, then rises to 170 DEG C with the speed of 2 DEG C per minute, and keep 5min, injector temperature is 220 DEG C, and hydrogen flame ionization detector temperature is 250 DEG C.
the preparation of control medicinal material solutionprecision takes muscone's control medicinal material and adds the ultrasonic process of methyl alcohol, and insolubles discards, and makes the control medicinal material solution of every 1ml containing muscone 20mg, shakes up, filter, to obtain final product;
the preparation of reference substance solutionprecision takes muskone reference substance and adds methyl alcohol and make every 1ml containing the reference substance solution of muskone 1mg, shakes up, filters, to obtain final product;
the preparation of need testing solutionget the Chinese patent drug bear gall pills for curing heart disease containing muscone, porphyrize, gets about 5g, accurately weighed, put in tool plug conical flask, add diethyl ether 50ml, weighed weight, water-bath refluxes 30 minutes, lets cool, weighed weight again, supplies the weight of less loss with ether, filter, filtrate water bath method, add methyl alcohol dissolving and be settled to 2 milliliters, shake up, to obtain final product.
determination methodaccurate absorption control medicinal material solution, reference substance solution and each 1 μ l of need testing solution respectively, inject gas chromatograph measures, and measures, to obtain final product.
In conjunction with muscone's control medicinal material and muskone reference substance collection of illustrative plates, first determine the chromatographic peak 5 i.e. retention time of muskone chromatographic peak in muscone's control medicinal material collection of illustrative plates; In muscone's control medicinal material collection of illustrative plates, again with muskone 5 for main peak, the peak occurred at its front 1-3 minute is musk lactone 1, the peak occurred at 0.5-1.5 minute is thereafter 4-methylcyclopentadecanone 4, the peak occurred at 2-4 minute is thereafter dehydrogenation musk lactone 2, and the peak occurred at 11.5-12.5 minute is thereafter C
18h
280
33, determine the chromatographic peak retention time of 1-4 successively; Muscone's control medicinal material collection of illustrative plates and sample collection of illustrative plates are contrasted, result shows, and retention time corresponding on bear gall pills for curing heart disease test sample collection of illustrative plates demonstrates grease 1,2,3,4 and muskone chromatographic peak, therefore, can judge that this medicine employs medicinal muscone.
Claims (9)
1. a muscone's detection method, is characterized in that, muskone, the 4-methylcyclopentadecanone of muscone in qualitative detection medicine, and musk lactone, dehydrogenation musk lactone and C
18h
280
3at least one in three kinds of compositions, if containing above composition, then judge that this drug use meets the medicinal muscone of States Pharmacopoeia specifications.
2. the detection method of a kind of muscone according to claim 1, is characterized in that, uses muskone, the 4-methylcyclopentadecanone of muscone in gas chromatography qualitative detection medicine, and musk lactone, dehydrogenation musk lactone and C
18h
280
3at least one in three kinds of compositions.
3. the detection method of a kind of muscone according to claim 2, is characterized in that, comprise the following steps:
(1) Chinese patent drug to be measured is prepared into need testing solution by the preparation of need testing solution;
(2) muscone's control medicinal material is made the control medicinal material solution of every 1ml containing muscone 20mg by the preparation of control medicinal material solution;
(3) reference substance solution of every 1ml containing muskone 1mg made by muskone reference substance by the preparation of reference substance solution;
(4) measure accurate absorption control medicinal material solution, reference substance solution and each 1 μ l of need testing solution respectively, inject gas chromatograph measures;
(5) by gas chromatogram, can detect in test sample collection of illustrative plates, with the muskone in muscone's control medicinal material collection of illustrative plates, 4-methylcyclopentadecanone, and musk lactone, dehydrogenation musk lactone and C
18h
280
3there is chromatographic peak in the identical retention time place of at least one in three kinds of compositions, can go out this sample and use the medicinal muscone meeting States Pharmacopoeia specifications by Qualitive test.
4. the detection method of a kind of muscone according to claim 3, it is characterized in that, in mensuration process, GC conditions is: column temperature is temperature programme, initial temperature is 140 ± 5 DEG C, keep 10 ± 2min, then rise to 170 ± 5 DEG C with the speed of 2-3 per minute DEG C, keep 5 ± 2min, injector temperature is 220 ± 5 DEG C, and hydrogen flame ionization detector temperature is 250 DEG C.
5. the detection method of a kind of muscone according to claim 3, it is characterized in that, in mensuration process, GC conditions is: column temperature is temperature programme, initial temperature is 140 DEG C, keep 10min, then rise to 170 DEG C with the speed of 2 DEG C per minute, keep 5min, injector temperature is 220 DEG C, and hydrogen flame ionization detector temperature is 250 DEG C.
6. the detection method of a kind of muscone according to claim 3, is characterized in that, step (1) is specially: get Chinese patent drug 5g to be measured, accurately weighed, put in tool plug conical flask, add diethyl ether 50ml, weighed weight, water-bath refluxes 30 minutes, lets cool, weighed weight again, supplies the weight of less loss with ether, filter, filtrate water bath method, adds methyl alcohol and dissolves, be settled to 2 milliliters, shake up, to obtain final product.
7. the detection method of a kind of muscone according to claim 3, is characterized in that, step (2) is specially: precision takes muscone's control medicinal material and adds the ultrasonic process of methyl alcohol, insolubles discards, shake up, filter, make the control medicinal material solution of every 1ml containing muscone 20mg.
8. the detection method of a kind of muscone according to claim 3, is characterized in that, step (3) is specially: precision takes muskone reference substance and adds methyl alcohol, shakes up, and filters, and makes the reference substance solution of every 1ml containing muskone 1mg.
9. the detection method of a kind of muscone according to claim 3, is characterized in that, muskone, the 4-methylcyclopentadecanone of muscone in step (5), and musk lactone, dehydrogenation musk lactone and C
18h
280
3at least one chromatographic peak determination methods in three kinds of compositions is:
1. muskone chromatographic peak in muscone's control medicinal material collection of illustrative plates is determined by main peak retention time in muskone reference substance collection of illustrative plates;
2. in muscone's control medicinal material collection of illustrative plates, take muskone as main peak, the peak occurred at its front 1-3 minute is musk lactone chromatographic peak, the peak occurred at 0.5-1.5 minute is thereafter 4-methylcyclopentadecanone chromatographic peak, the peak occurred at 2-4 minute is thereafter dehydrogenation musk lactone chromatographic peak, and the peak occurred at 11.5-12.5 minute is thereafter C
18h
280
3chromatographic peak, determines 4-methylcyclopentadecanone, musk lactone, dehydrogenation musk lactone and C respectively
18h
280
3chromatographic peak retention time, thus provide foundation for Qualitive test sample.
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