CN108164464B - A kind of analysis method that can be kept completely separate (-)-huperzine Yu (+)-huperzine - Google Patents
A kind of analysis method that can be kept completely separate (-)-huperzine Yu (+)-huperzine Download PDFInfo
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- CN108164464B CN108164464B CN201810115692.2A CN201810115692A CN108164464B CN 108164464 B CN108164464 B CN 108164464B CN 201810115692 A CN201810115692 A CN 201810115692A CN 108164464 B CN108164464 B CN 108164464B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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- 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
- G01N30/50—Conditioning of the sorbent material or stationary liquid
- G01N30/52—Physical parameters
- G01N30/54—Temperature
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- 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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- 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
- G01N30/89—Inverse chromatography
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- 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
- G01N2030/027—Liquid chromatography
Abstract
The present invention relates to a kind of analysis methods that can be kept completely separate (-)-huperzine Yu (+)-huperzine, including the following contents: by the injection of the mixed solution of (-)-huperzine of preparation and (+)-huperzine using poly sugar derivatives to be rinsed and being separated with the flow visualizing that acetonitrile or alcohols form with ammonium acetate solution in the high performance liquid chromatograph of stationary phase.Detection method of the invention not only can intuitively reflect the quality of product and provide help for resolution process by the content of (+)-huperzine in testing product；Although and this method uses reverse-phase chromatography condition, Liquid apparatus is not necessarily to carry out the switching of positive reverse phase, time saving and energy saving to save trouble using chiral chromatographic column；Chromatographic column, can also be adjusted to prepare column by analysis method of the invention, prepare (-)-huperzine for fractionation.
Description
Technical field
The present invention relates to pharmaceutical technology fields, and in particular to a kind of to be kept completely separate (-)-huperzine and (+)-huperzine
The analysis method of first.
Background technique
Huperzine: chemical name is (1R, 9S, 13E) -1- amino -13- ethylidene -11- methyl -6- aza-tricycle
[7.3.1.0] ten three -2 (7), 3,10- triolefin -5- ketone, molecular weight 242.
This product is a kind of Reversible cholinesterase inhibitor, has selective inhibitory to true cholinesterase.Biology
It is active high, have higher fat-soluble, molecule is small, easily penetrate blood-brain barrier, into maincenter after be more distributed in brain frontal lobe,
Temporal lobe, hippocampus etc. have the brain area of close ties with learning and memory, have under low dosage to acetylcholinesterase (AChE) powerful
Inhibiting effect, keep acetylcholine (ACh) content in nerve synapse gap in distributed area significantly raised, so that it is emerging to enhance neuron
It puts forth energy to conduct, the excitation of intensified learning and memory brain area, plays and improve cognitive function, enhancing memory keeps and promotes memory again
Existing effect.It has now been found that the conjugation of (+)-huperzine and acetylcholine is poor, is far below (-)-huperzine.It is artificial to close
At method obtain be (±)-huperzine racemic mixture, (-)-huperzine that obtain high-purity then needs
Mixture is separated.
Positive phase separation is used to the separation of (±)-huperzine isomers in the prior art, needs switching anti-first
Phase system is converted into positive phase system, needs to consume manpower and time, and often switching is lossy to equipment；Secondly, positive item
Chromatographic peak peak shape under part is poor, and theoretical cam curve is relatively low.At present there is no document report can be kept completely separate (-)-huperzine and
The reverse phase separation condition of (+)-huperzine.
Summary of the invention
The purpose of the present invention is to provide a kind of analysis sides that can be kept completely separate (-)-huperzine Yu (+)-huperzine
Method, theoretical cam curve, separating degree, tailing factor of the method etc. are all satisfied the requirement of Pharmaceutical Analysis detection, and it is convenient to detect, and are suitble to
In the separation and detection of (-)-huperzine and (+)-huperzine, solves the positive reverse phase of frequent switching existing in the prior art
System causes the loss to Liquid apparatus, consumes a large amount of manpowers and time；And the chromatographic peak peak shape under the conditions of positive is poor, reason
By the problem that the number of plates is relatively low.
To achieve the goals above, the present invention provides the following technical solution, a kind of to be kept completely separate (-)-huperzine
With the analysis method of (+)-huperzine, which comprises by reversed-phased high performace liquid chromatographic from contain (-)-huperzine
(-)-huperzine is isolated in the mixed solution of first and (+)-huperzine；(-)-huperzine and (+)-huperzine
It dissolves to obtain with the mixed solution of water and organic solvent；Mobile phase used in the high performance liquid chromatography is by mobile phase A and stream
Dynamic phase B composition: the mobile phase A is ammonium acetate solution, and the Mobile phase B is acetonitrile or alcohols；The high performance liquid chromatography
Stationary phase used includes poly sugar derivatives.
As a further improvement of the present invention, the concentration of (-)-huperzine and (+)-huperzine be 0.005~
2mg/mL, more preferably 0.01mg/mL.
As a further improvement of the present invention, in the mobile phase A ammonium acetate solution concentration range be 15~
25mmol/L, more preferably 20mmol/L.
As a further improvement of the present invention, the pH range of ammonium acetate solution is 5.5~6.5 in the mobile phase A, excellent
It is selected as 6.0.
As a further improvement of the present invention, the Mobile phase B is preferably acetonitrile, because the viscosity of acetonitrile is low, system pressure
Power is small；Cutoff wavelength is low to be conducive to baseline stability.
As a further improvement of the present invention, in the mixed solution of the water and organic solvent organic solvent be selected from acetonitrile or
Alcohol organic solvent, the alcohol organic solvent include methanol, ethyl alcohol or isopropanol；Because flowing phase composition generally contains acetonitrile, it is
Reduce solvent effect, the preferred acetonitrile of organic solvent.
As a further improvement of the present invention, the mixed solution of the water and organic solvent, to reduce solvent effect simultaneously
Consider that preferably 50% acetonitrile solution is prepared as solvent in conjunction with sample solubility.
As a further improvement of the present invention, when Mobile phase B is acetonitrile, to obtain better peak shape, gradient elution,
In 0~20 minute, the volume ratio of mobile phase A and Mobile phase B is 4~1:1.
As a further improvement of the present invention, the flow velocity used is 0.5~1.0mL/min, preferably 0.7mL/min.
As a further improvement of the present invention, the stationary phase includes poly sugar derivatives, including three (3,5- xylyls
Carbamate) amylose, three (3,5- xylyl carbamate) celluloses, three (the chloro- 4- MethYlphenylamino first of 3-
Acid esters) cellulose, or mixtures thereof three (3,5- Dichloro-phenylamino formic acid esters) celluloses, preferably surface is coated with three (3-
Chloro- 4- methyl phenyl carbamate) cellulose silica gel.
As a further improvement of the present invention, the column temperature range of chiral column used in the reversed-phased high performace liquid chromatographic is
30~40 DEG C, the low influence peak shape of temperature, temperature height is big to the loss of chromatographic column, and preferably column temperature is 35 DEG C.
As a further improvement of the present invention, the reversed-phased high performace liquid chromatographic is examined using ultraviolet lamp detector
It surveys, the Detection wavelength is 230~330nm, excludes low band, and selecting the absorption maximum of huperzine is Detection wavelength, preferably
310nm。
Compared with prior art, it is the advantages of analyzing detecting method of the present invention: (-)-huperzine can not only be completely separated
First and (+)-huperzine, and Liquid apparatus is not necessarily to carry out the switching of positive reverse phase, it is more convenient than positive phase system use, and flow
Phase composition is common, preparation is simple, save trouble and labor, and agents useful for same is lower relative to positive reagent price, escapable cost；Analysis
Time is short, time saving；Separating degree, tailing factor, theoretical cam curve have relatively satisfactory result.The present invention is analysis method, can also
It is adjusted to the chromatographic column to prepare column and is used for fractionation and prepares (-)-huperzine.
Detailed description of the invention
Fig. 1 is the HPLC map obtained according to embodiment 1.
Fig. 2 is the HPLC map obtained according to embodiment 2.
Fig. 3 is the HPLC map obtained according to embodiment 3.
Specific embodiment
For convenient for those skilled in the art understand that the content of present invention, further describes this hair below in conjunction with specific embodiment
Bright technical solution, but the following contents should not in any way limit the claimed range of claims of the present invention.
" retention time ", " separating degree ", " tailing factor ", the paraphrase of " theoretical cam curve " and the following institute of formula in embodiment
Show:
Retention time (tR): refer to sample from sample introduction to the time needed for the maximum chromatography peak response of sample appearance through eluting.
Separating degree (Rs): refer to the separation situation of two components in certain mixture.It can be calculated by the following formula:
Rs=2 (tR2-tR1)(W1+W2)
In formula, tR2And tR1The respectively retention time of two substances, W1And W2Respectively in the corresponding peak width of its base portion, by this
Peak extends relatively straight both sides to baseline and intersects acquisition.
Tailing factor (As): i.e. symmetrical factor can be calculated by the following formula:
As=W0.05/2f
In formula, W0.05It is the peak width at peak height 5%, f is peak maximum to the distance between peak forward position, this distance should be from baseline
It is measured at the 5% of the above peak height.
Theoretical cam curve (N): being the balancing method of column effect.It can be calculated by the following formula:
N=16 (tR/W)2
In formula, tRIt is the retention time of the substance；W is peak width of this peak in its base portion, extends relatively straight two by the peak
It is obtained while intersecting to baseline.
Embodiment 1
Experiment condition:
Equipment: 1260 high performance liquid chromatograph of Agilent.
Chromatographic column: being coated with three (the chloro- 4- methyl phenyl carbamates of 3-) using Silica Surface, cellulose is stationary phase, greatly
Match 5 μm of 4.6mm × 250mm of fine jade CHIRALCEL OZ-RH.
Mobile phase A is 20mmol/L ammonium acetate solution, and pH 6.0, Mobile phase B is acetonitrile, gradient elution, at 0~20 point
In clock, the volume ratio of mobile phase A and Mobile phase B is 4~1:1；Flow velocity is 0.7mL/min, Detection wavelength 310nm, column temperature 35
DEG C, 5 μ L of sample volume.
The preparation of system suitability solution: (-)-huperzine and (+)-huperzine is taken to be prepared with 50% acetonitrile solution
It is respectively the mixed solution of 0.01mg/mL at concentration.It takes in above-mentioned solution injection liquid chromatograph, records chromatogram, investigate separation
Degree, tailing factor, theoretical cam curve.
As shown in Figure 1, parameters see the table below HPLC analysis chart:
Embodiment 2
Experiment condition:
Equipment: 1260 high performance liquid chromatograph of Agilent.
Chromatographic column: being coated with three (the chloro- 4- methyl phenyl carbamates of 3-) using Silica Surface, cellulose is stationary phase, greatly
Match 5 μm of 4.6mm × 250mm of fine jade CHIRALCEL OZ-RH.
Mobile phase A is 15mmol/L ammonium acetate solution, and pH 5.5, Mobile phase B is acetonitrile, gradient elution, at 0~20 point
In clock, the volume ratio of mobile phase A and Mobile phase B is 4~1:1；Flow velocity is 1.0mL/min, Detection wavelength 310nm, column temperature 40
DEG C, 5 μ L of sample volume.
The preparation of system suitability solution: (-)-huperzine and (+)-huperzine is taken to be prepared with 50% acetonitrile solution
It is respectively the mixed solution of 0.01mg/mL at concentration.It takes in above-mentioned solution injection liquid chromatograph, records chromatogram, investigate separation
Degree, tailing factor, theoretical cam curve.
As shown in Figure 2, parameters see the table below HPLC analysis chart:
Embodiment 3
Experiment condition:
Equipment: 1260 high performance liquid chromatograph of Agilent.
Chromatographic column: being coated with three (the chloro- 4- methyl phenyl carbamates of 3-) using Silica Surface, cellulose is stationary phase, greatly
Match 5 μm of 4.6mm × 250mm of fine jade CHIRALCEL OZ-RH.
Mobile phase A is 25mmol/L ammonium acetate solution, and pH 6.5, Mobile phase B is acetonitrile, gradient elution, at 0~20 point
In clock, the volume ratio of mobile phase A and Mobile phase B is 4~1:1；Flow velocity is 0.5mL/min, Detection wavelength 310nm, column temperature 30
DEG C, 5 μ L of sample volume.
The preparation of system suitability solution: (-)-huperzine and (+)-huperzine is taken to be prepared with 50% acetonitrile solution
It is respectively the mixed solution of 0.01mg/mL at concentration.It takes in above-mentioned solution injection liquid chromatograph, records chromatogram, investigate separation
Degree, tailing factor, theoretical cam curve.
As shown in attached drawing 3, parameters see the table below HPLC analysis chart:
Claims (14)
1. a kind of analysis method that can be kept completely separate (-)-huperzine Yu (+)-huperzine, which is characterized in that the method
It is made of following operation:
It is isolated from the mixed solution containing (-)-huperzine and (+)-huperzine by reversed-phased high performace liquid chromatographic
(-)-huperzine；The mixed solution of (-)-huperzine and (+)-huperzine water and organic solvent dissolves to obtain,
The organic solvent is acetonitrile；Mobile phase used in the reversed-phased high performace liquid chromatographic is made of mobile phase A and Mobile phase B:
The mobile phase A is ammonium acetate solution；
The Mobile phase B is acetonitrile or alcohols；
Stationary phase used in the reversed-phased high performace liquid chromatographic is made of poly sugar derivatives, and the poly sugar derivatives is three
(the chloro- 4- methyl phenyl carbamate of 3-) cellulose.
2. analysis method according to claim 1, it is characterised in that: (-)-huperzine and (+)-huperzine
Concentration is respectively 0.005~2mg/mL.
3. analysis method according to claim 2, it is characterised in that: (-)-huperzine and (+)-huperzine
Concentration is respectively 0.01mg/mL
4. analysis method according to claim 1, it is characterised in that: the concentration of ammonium acetate solution in the mobile phase A
For 15~25mmol/L.
5. analysis method according to claim 4, it is characterised in that: the concentration of ammonium acetate solution in the mobile phase A
For 20mmol/L.
6. analysis method according to claim 4, it is characterised in that: the pH of ammonium acetate solution is in the mobile phase A
5.5~6.5.
7. analysis method according to claim 6, it is characterised in that: the pH of ammonium acetate solution is in the mobile phase A
6.0。
8. analysis method according to claim 1, it is characterised in that: when Mobile phase B is acetonitrile, gradient elution, 0~
In 20 minutes, the volume ratio of mobile phase A and Mobile phase B is 4~1:1.
9. analysis method according to claim 1, which is characterized in that the flow velocity of mobile phase is 0.5~1.0mL/min.
10. analysis method according to claim 9, which is characterized in that the flow velocity of mobile phase is 0.7mL/min.
11. described in any item analysis methods according to claim 1~10, it is characterised in that: the reversed-phase high performance liquid chromatography
The column temperature of chiral column used in method is 30~40 DEG C.
12. analysis method according to claim 11, it is characterised in that: the column temperature of the chiral column is 35 DEG C.
13. described in any item analysis methods according to claim 1~10, it is characterised in that: the reversed-phase high performance liquid chromatography
Method is detected using ultraviolet lamp detector, and the wavelength of ultraviolet light is 230~330nm.
14. analysis method according to claim 13, it is characterised in that: the wavelength of the ultraviolet light is 310nm.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102288703A (en) * | 2011-07-29 | 2011-12-21 | 江南大学 | Method for rapidly detecting phenyllactic acid isomer by reversed phase high performance liquid chromatogram |
| CN105044269A (en) * | 2015-06-30 | 2015-11-11 | 成都百裕科技制药有限公司 | Method for detecting initial material II in apixaban through reversed-phase high performance liquid chromatography |
| CN106996964A (en) * | 2017-04-20 | 2017-08-01 | 山东赛托生物科技股份有限公司 | Method and the application of hydroxypropyl beta cyclodextrin using reversed-phased high performace liquid chromatographic separating chiral enantiomer |
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2018
- 2018-02-06 CN CN201810115692.2A patent/CN108164464B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102288703A (en) * | 2011-07-29 | 2011-12-21 | 江南大学 | Method for rapidly detecting phenyllactic acid isomer by reversed phase high performance liquid chromatogram |
| CN105044269A (en) * | 2015-06-30 | 2015-11-11 | 成都百裕科技制药有限公司 | Method for detecting initial material II in apixaban through reversed-phase high performance liquid chromatography |
| CN106996964A (en) * | 2017-04-20 | 2017-08-01 | 山东赛托生物科技股份有限公司 | Method and the application of hydroxypropyl beta cyclodextrin using reversed-phased high performace liquid chromatographic separating chiral enantiomer |
Non-Patent Citations (2)
| Title |
|---|
| 反相高效液相色谱法拆分匹诺塞林对映异构体;杨庆云,原悦,戚燕,童元峰,吴松;《药物分析杂志》;20101231;第30卷(第1期);第88-91页 |
| 石杉碱甲的研究进展;许明，宋新波，张丽娟;《Drug Evaluation Research》;20101231;第33卷(第6期);第442-446页 |
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