CN105954431A - Method for measuring substances relevant to ospemifene raw medicine through HPLC (high performance liquid chromatography) separation - Google Patents
Method for measuring substances relevant to ospemifene raw medicine through HPLC (high performance liquid chromatography) separation Download PDFInfo
- Publication number
- CN105954431A CN105954431A CN201610544063.2A CN201610544063A CN105954431A CN 105954431 A CN105954431 A CN 105954431A CN 201610544063 A CN201610544063 A CN 201610544063A CN 105954431 A CN105954431 A CN 105954431A
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- CN
- China
- Prior art keywords
- crude drug
- related substance
- ospemifene
- pei meter
- hplc separation
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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
-
- 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 invention relates to a method for measuring substances relevant to ospemifene raw medicine through HPLC (high performance liquid chromatography) separation. The method comprises the following steps that octadecylsilane bonded silica gel is used as a filling agent; phosphoric acid is used for regulating the water pH to 2.5 to 2.5 for performing gradientelution as a flowing phase A; methyl alcohol-acetonitrile is used as a flowing phase B to perform gradientelution; the flowing speed is 0.8 to 1.2mL/min; the column temperature is 32 to 37 DEG C; an ultraviolet detector is used for detecting substances relevant to the ospemifene raw medicine. The method provided by the invention has the advantages of high speed, simplicity, convenience, high sensitivity, accuracy and reliability, and is suitable for being used for separating and measuring the substances relevant to ospemifene raw medicine. The method provided by the invention has the advantages that the detection result reaches the optimization through the overall consideration of the analytical column, the flowing phase and the gradient elution procedures and the overall influence of the flowing speed and the column temperature on the separation detection; the advantages of high speed, simplicity, convenience, high sensitivity, accuracy and reliability are realized; the method is suitable for being used for separating and measuring the substances relevant to the ospemifene raw medicine.
Description
Technical field
The present invention relates to the analysis determining method of a kind of Ao Pei meter Fen crude drug, be specifically related to one HPLC separation determination
Ao Pei meter Fen crude drug has the method for related substance.
Background technology
Ao Pei meter Fen is a kind of estrogen-agonistic medicine with tissue selectivity effect and antagonistic.Estrogen is subject to by this medicine
Body α (ER α) and β (ER β) has affinity.Its biological action is by being combined mediation with estrogen receptor.This kind combines
Cause the activation (agonism) of estrogen pathway in some is organized and block other estrogen pathway (antagonism), molecule
Formula is C24H23ClO2, molecular weight is 378.9, and structural formula is as follows:
In order to control the quality of Ao Pei meter Fen crude drug, need main component and impurity to be controlled, in existing skill
In art, it is not suitable for analysis method quick, easy, that Accurate Analysis detection Ao Pei meter Fen crude drug has related substance.
Therefore, Ao Pei meter Fen crude drug is further improved and optimization demand with the presence of the assay method of related substance,
This power that present invention is accomplished just and starting point place.
Summary of the invention
For the above-mentioned technical problem overcoming prior art to exist, the present inventor carried out substantial amounts of further investigation it
After, thus provide a kind of method that HPLC separation determination Ao Pei meter Fen crude drug has related substance, have fast and convenient, sensitive
Degree height, accurately and reliably advantage.
The present invention is achieved through the following technical solutions, former in particular to one HPLC separation determination Ao Pei meter Fen
The method that material medicine has related substance, comprises the steps: with octadecylsilane chemically bonded silica as filler, with phosphoric acid water transfer pH extremely
2.5～3.5 is that Mobile phase B carries out gradient elution for mobile phase A, methanol-acetonitrile, and flow velocity is 0.8～1.2mL/min, and column temperature is
32～37 DEG C, UV-detector is used to have related substance to detect Ao Pei meter Fen crude drug.
Preferably, the particle diameter of described octadecylsilane chemically bonded silica is 5 μm, and column internal diameter is 4.6mm, and column length is 250mm.
Preferably, with phosphoric acid water transfer pH to 3.0 as mobile phase A.
Preferably, in described Mobile phase B, the volume ratio of methanol and acetonitrile is 30: 70.
Preferably, when gradient elution, flow velocity is 1.0mL/min, and column temperature is 35 DEG C.
Preferably, the detailed process of described gradient elution is:
Preferably, the detection wavelength of described UV-detector is 230nm.
Compared with prior art, beneficial effects of the present invention is as follows: the inventive method is by considering analytical column, flowing
Phase, gradient elution program and flow velocity, the column temperature combined influence to separation detection so that testing result has reached optimization, tool
Have fast and convenient, highly sensitive, advantage accurately and reliably, it is adaptable to separation determination Ao Pei meter Fen crude drug have related substance.
Accompanying drawing explanation
Fig. 1 is the liquid phase spectrogram that Ao Pei meter Fen has related substance.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is described in detail.Following example will assist in the technology of this area
Personnel are further appreciated by the present invention, but limit the present invention the most in any form.It should be pointed out that, the ordinary skill to this area
For personnel, without departing from the inventive concept of the premise, it is also possible to make some deformation and improvement.These broadly fall into the present invention
Protection domain.
A kind of method that HPLC separation determination Ao Pei meter Fen crude drug has related substance, comprises the steps: with octadecane
Base silane bonded silica gel is filler, and the particle diameter of octadecylsilane chemically bonded silica is 5 μm, and column internal diameter is 4.6mm, and column length is
250mm, with phosphoric acid water transfer pH to 3.0 as mobile phase A, volume ratio be 30: 70 methanol-acetonitrile for flowing phase, carry out gradient and wash
De-, gradient elution program is shown in Table 1, and flow velocity is 1.0mL/min, and column temperature is 35 DEG C, uses UV-detector to Ao Pei meter Fen raw material
The related substance that has of medicine detects, and detection wavelength is that the liquid phase spectrogram of 230nm, Ao Pei meter Fen crude drug sample is as it is shown in figure 1, Austria
The peak value of Pei meter Fen crude drug sample is as shown in table 2.
Table 1 gradient elution program
| Time (minute) | Mobile phase A (volume %) | Mobile phase B (volume %) |
| 0 | 50 | 50 |
| 8 | 50 | 50 |
| 12 | 35 | 65 |
| 35 | 25 | 75 |
| 60 | 10 | 90 |
| 60.1 | 50 | 50 |
| 70 | 50 | 50 |
The peak value meter of table 2 Ao Pei meter Fen crude drug
| Peak is numbered | Retention time min | Highly mAu | Area mAu*s | Area % | Tailing factor | Theoretical cam curve | Separating degree |
| A | 8.065 | 15.95 | 216.87 | 0.745 | 0.903 | 7519 | |
| B | 8.679 | 19.75 | 274.91 | 0.945 | 0.949 | 8746 | 1.6 |
| C | 12.498 | 18.32 | 267.33 | 0.919 | 0.969 | 15898 | 9.9 |
| D | 14.119 | 16.20 | 210.39 | 0.723 | 0.891 | 27612 | 4.4 |
| E | 18.060 | 16.64 | 208.82 | 0.718 | 0.973 | 45172 | 11.6 |
| F | 30.086 | 20.11 | 314.15 | 1.079 | 1.017 | 83924 | 31.8 |
| Principal agent | 31.179 | 1681.74 | 27109.74 | 93.147 | 1.048 | 85837 | 2.6 |
| G | 32.075 | 14.30 | 239.60 | 0.823 | 0.933 | 85762 | 2.1 |
| H | 34.090 | 15.39 | 262.60 | 0.902 | 1.030 | 90517 | 4.5 |
System suitability: take Ao Pei meter Fen and impurity A, B, C, D, E, F, G, H reference substance respectively appropriate, accurate claims
Fixed, put in same volumetric flask, add methanol appropriate, ultrasonic make dissolving dilution make in every 1mL containing about Ao Pei meter Fen 0.5mg, contain
Each impurity is about the mixed solution of 5 μ g, and each peak separating degree should be not less than 1.5.
Concrete test operation: take this product appropriate, add methanol dissolve and quantitatively dilution make in every 1mL containing about 0.5mg molten
Liquid measures 1mL as need testing solution, precision, puts in 100mL measuring bottle, with solvent dilution to scale, as contrast solution.It is right to take
According to solution 20 μ L inject chromatograph of liquid, regulate detection sensitivity, make main constituent chromatographic peak peak height is full scale 10%～
20%.Precision measures need testing solution and each 20 μ L of contrast solution again, is injected separately into chromatograph of liquid, records chromatogram.For examination
If any impurity peaks in the chromatogram of product solution, single impurity peak area cannot be greater than 0.10 times of contrast solution main peak area
(0.10%), the sum of each impurity peak area, cannot be greater than 1.0 times (1.0%) of the main peak area of contrast solution.(impurity C, miscellaneous
Matter D, impurity E correction factor are respectively 0.74,0.80,0.80；Remaining known impurities and unknown impuritie correction factor are based on 1.0
Calculate).
Computing formula:
Total miscellaneous content=Σ other impurity contents of known impurity level+Σ
ASingle: impurity peak area AComparison: 1% comparison main peak area F: correction factor
| Impurity title | Relative retention time | Correction factor (F) |
| Impurity A | 0.26 | 0.92 |
| Impurity B | 0.28 | 1.06 |
| Impurity C | 0.40 | 0.74 |
| Impurity D | 0.45 | 0.80 |
| Impurity E | 0.58 | 0.80 |
| Impurity F | 0.96 | 1.00 |
| Impurity G | 1.03 | 0.92 |
| Impurity H | 1.09 | 1.04 |
Above the specific embodiment of the present invention is described.It is to be appreciated that the invention is not limited in above-mentioned
Particular implementation, those skilled in the art can make various deformation or amendment within the scope of the claims, this not shadow
Ring the flesh and blood of the present invention.
Claims (7)
1. the method having related substance with HPLC separation determination Ao Pei meter Fen crude drug, it is characterised in that comprise the steps:
With octadecylsilane chemically bonded silica as filler, with phosphoric acid water transfer pH to 2.5～3.5 as mobile phase A, methanol-acetonitrile be stream
Dynamic phase B carries out gradient elution, and flow velocity is 0.8～1.2mL/min, and column temperature is 32～37 DEG C, uses UV-detector to Ao Pei meter
The related substance that has of fragrant crude drug detects.
2. the method having related substance with HPLC separation determination Ao Pei meter Fen crude drug as claimed in claim 1, it is characterised in that
The particle diameter of described octadecylsilane chemically bonded silica is 5 μm, and column internal diameter is 4.6mm, and column length is 250mm.
3. the method having related substance with HPLC separation determination Ao Pei meter Fen crude drug as claimed in claim 1, it is characterised in that
With phosphoric acid water transfer pH to 3.0 as mobile phase A.
4. the method having related substance with HPLC separation determination Ao Pei meter Fen crude drug as claimed in claim 1, it is characterised in that
In described Mobile phase B, the volume ratio of methanol and acetonitrile is 30: 70.
5. the method having related substance with HPLC separation determination Ao Pei meter Fen crude drug as claimed in claim 1, it is characterised in that
When gradient elution, flow velocity is 1.0mL/min, and column temperature is 35 DEG C.
6. the method having related substance with HPLC separation determination Ao Pei meter Fen crude drug as claimed in claim 1, it is characterised in that
The detailed process of described gradient elution is:
7. the method having related substance with HPLC separation determination Ao Pei meter Fen crude drug as claimed in claim 1, it is characterised in that
The detection wavelength of described UV-detector is 230nm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610544063.2A CN105954431B (en) | 2016-07-11 | 2016-07-11 | A kind of method of the HPLC separation determination Ao Pei meter Fen bulk pharmaceutical chemicals in relation to substance |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610544063.2A CN105954431B (en) | 2016-07-11 | 2016-07-11 | A kind of method of the HPLC separation determination Ao Pei meter Fen bulk pharmaceutical chemicals in relation to substance |
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| CN105954431A true CN105954431A (en) | 2016-09-21 |
| CN105954431B CN105954431B (en) | 2018-05-29 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114088821A (en) * | 2021-08-26 | 2022-02-25 | 陕西新时代生物转化检测有限公司 | Method for detecting domiphen bromide content in disinfection product |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014060640A1 (en) * | 2012-10-19 | 2014-04-24 | Fermion Oy | A process for the preparation of ospemifene |
-
2016
- 2016-07-11 CN CN201610544063.2A patent/CN105954431B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014060640A1 (en) * | 2012-10-19 | 2014-04-24 | Fermion Oy | A process for the preparation of ospemifene |
| JP2015532309A (en) * | 2012-10-19 | 2015-11-09 | フェルミオン オサケ ユキチュア | Ospemifen production method |
Non-Patent Citations (4)
| Title |
|---|
| JOUKO UUSITALO 等: "Metabolism and metabolite profiles in vivo and in vivo of ospermifene in humans and preclinical species", 《DRUG METABOL PERS THER》 * |
| MITTA CHAITANYA 等: "Method development for the simultaneous estimation of ospemifine by using RP-HPLC", 《INTERNATIONAL JOURNAL OF PHARMA RESEARCH AND HEALTH SCIENCES》 * |
| TRACY L. TARAS 等: "Quantitative analysis of Z-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol in human plasma using high-performance liquid chromatography", 《JOURNAL OF CHROMATOGRAPHY B》 * |
| 郝晨洲: "奥培米芬(Ospemifene)", 《中国药物化学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114088821A (en) * | 2021-08-26 | 2022-02-25 | 陕西新时代生物转化检测有限公司 | Method for detecting domiphen bromide content in disinfection product |
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