CN110376309A - A method of replacing the related substance of Buddhist nun in measurement west difficult to understand - Google Patents
A method of replacing the related substance of Buddhist nun in measurement west difficult to understand Download PDFInfo
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- CN110376309A CN110376309A CN201910754094.4A CN201910754094A CN110376309A CN 110376309 A CN110376309 A CN 110376309A CN 201910754094 A CN201910754094 A CN 201910754094A CN 110376309 A CN110376309 A CN 110376309A
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- understand
- buddhist nun
- ammonium acetate
- substance
- acetonitrile
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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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/36—Control of physical parameters of the fluid carrier in high pressure liquid systems
-
- 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
-
- 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
-
- 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
- G01N2030/062—Preparation extracting sample from raw material
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- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention discloses a kind of measurement west difficult to understand to replace method of the Buddhist nun in relation to substance, using HPLC analytical method, select octadecylsilane chemically bonded silica chromatographic column, gradient elution is carried out by mobile phase of ammonium acetate solution-acetonitrile of mass concentration 0.05%, flow velocity is 0.9-1.2ml/min, and column temperature is 30-32 DEG C；0.05% ammonium acetate solution and acetonitrile carries out gradient elution: 85-90%:10-15%, 0-5min in the following proportions；40-55%:45-60%, 25-35min;85-90%:10-15%, 36-46min.Institute's construction method is easy to operate, quick, reproducible, can be used for west difficult to understand for the quality control and preparation production of Buddhist nun's bulk pharmaceutical chemicals.
Description
Technical field
The invention belongs to Pharmaceutical Analysis technical fields, it particularly relates to which side of the Buddhist nun in relation to substance is replaced in a kind of measurement west difficult to understand
Method.
Background technique
Epidermal growth factor recipient tyrosine kinase (EGFR-TK) is the important target molecule of oncotherapy.EGFR-TKIs)
With high susceptibility, Gefitinib and Tarceva are that it represents drug, are shown according to correlative study, Gefitinib and E Luo are replaced
The effective percentage of Buddhist nun can reach 70% -80%, and middle position PFS 7.7-13.3 months.Therefore, it is recommended as EGFR by guide to dash forward
Become the first-line treatment scheme of positive advanced NSCLC patients.However, after treatment in 9-14 months, most of EGFR mutation sun
Initially the patient sensitive to EGFR-TKI will appear progression of disease to property, wherein about 50% medicament-resistant mutation is by acquired
Caused by T790M is mutated.
West difficult to understand for Buddhist nun (Tai Ruisha, AZD9291) be as Astrazeneca AB, Britain research and develop can simultaneously for EGFR at the beginning of
The third generation EGFR-TKI in beginning mutation and the mutational site T790M, and the 3rd generation EGFR-TKI of the first approval listing in the whole world,
It is listed in May, 2017 in China, receives to occur after EGFR-TKIs is treated the non-small thin of EGFR-T790M mutation for treating
Born of the same parents' lung cancer.1st generation EGFR-TKIs drug resistance, 2nd generation EGFR-TKI drug resistance and selective problems are overcome, while there is high target
The advantages of tropism low ADR.The medicine shows promise as the first-line treatment of EGFR-T790M positive NSCLC patient (with brain metastes)
Drug.But Buddhist nun's bulk pharmaceutical chemicals assay and quality standard research are replaced in current only a small amount of document report west difficult to understand, replace to reinforce west difficult to understand
The quality of Buddhist nun controls, and it is very urgent for the method for the related substance in Buddhist nun to research and develop a kind of measurement west difficult to understand.
Summary of the invention
The technical issues of for west difficult to understand for the control of Buddhist nun's mass, the present invention provides a kind of measurement west difficult to understand for the related substance of Buddhist nun
Method measures the method that Buddhist nun's bulk pharmaceutical chemicals content is replaced in west difficult to understand using HPLC, and institute's construction method is easy to operate, quick, reproducible, can use
Yu Aoxi produces for the quality control of Buddhist nun's bulk pharmaceutical chemicals and preparation.
To achieve the above object, the technology originating party case that the present invention uses is:
A method of the related substance of Buddhist nun is replaced in measurement west difficult to understand, using HPLC analytical method, selects octadecyl
Silane group silica gel chromatographic column carries out gradient elution, flow velocity by mobile phase of ammonium acetate solution-acetonitrile of mass concentration 0.05%
For 0.9-1.2ml/min, column temperature is 30-32 DEG C；0.05% ammonium acetate solution and acetonitrile carries out gradient elution in the following proportions:
85-90%:10-15%, 0-5min；40-55%:45-60%, 25-35min；85-90%:10-15%, 36-46min.
Method of the Buddhist nun in relation to substance is replaced in measurement of the present invention west difficult to understand, and the ammonium acetate solution uses hydrochloric acid tune pH value
To 8-9.
After sample is first used mobile phase solution predissolve by the present invention, then carry out gradient elution.
Preferably, in the mobile phase solution for predissolve, the volume ratio of ammonium acetate solution and acetonitrile is 30:70.
Detection wavelength of the invention is 240~260nm；Sample volume is 20 μ L.
Of the present invention 0.05% ammonium acetate solution and acetonitrile carries out gradient elution: 90%:10%, 0- in the following proportions
5min；40%:60%, 25-35min；90%:10%, 36-46min.
The beneficial effects of the present invention are:
1, the present invention comprehensively considers the sensitivity of temperature and ph and devises the related substances according to the solubility of sample
Measurement, adjust various conditions of the Ao Xini in relation to substance HPLC, and integrity authentication carried out to involved condition, having proven to can
Standard solution and sample detection is enabled to reach exclusive, accurately, accurate, quantitative and stable analysis purpose.
2, west difficult to understand can be efficiently separated out for the impurity in Buddhist nun, baseline is noiseless, and specificity is strong, and method is effectively, reliably；It can be tight
Replace Buddhist nun's bulk pharmaceutical chemicals quality, reproducibility 100% in lattice control west difficult to understand.
Detailed description of the invention
Fig. 1 is that the HPLC chromatogram in relation to substance in Buddhist nun's bulk pharmaceutical chemicals is replaced in Austria west that measuring method of the present invention obtains.A is blank
Solvent chromatogram, B are west difficult to understand for Buddhist nun's test sample.
Specific embodiment
The embodiment of the present invention is described in detail with reference to the accompanying drawing.
Embodiment 1
A method of the related substance of Buddhist nun is replaced in measurement west difficult to understand, using HPLC analytical method, selects octadecyl
Silane group silica gel chromatographic column carries out gradient elution, flow velocity by mobile phase of ammonium acetate solution-acetonitrile of mass concentration 0.05%
For 0.9ml/min, column temperature is 30 DEG C；0.05% ammonium acetate solution and acetonitrile carries out gradient elution in the following proportions: 85%:
15%, 0-5min；40%:60%, 25-35min；85%:15%, 36-46min.
Embodiment 2
A method of the related substance of Buddhist nun is replaced in measurement west difficult to understand, using HPLC analytical method, selects octadecyl
Silane group silica gel chromatographic column carries out gradient elution, flow velocity by mobile phase of ammonium acetate solution-acetonitrile of mass concentration 0.05%
For 1.2ml/min, column temperature is 32 DEG C；0.05% ammonium acetate solution and acetonitrile carries out gradient elution in the following proportions: 90%:
10%, 0-5min；55%:45%, 25-35min；90%:10%, 36-46min.
The ammonium acetate solution is using hydrochloric acid tune pH value to 8.
Embodiment 3
A method of the related substance of Buddhist nun is replaced in measurement west difficult to understand, using HPLC analytical method, selects octadecyl
Silane group silica gel chromatographic column carries out gradient elution, flow velocity by mobile phase of ammonium acetate solution-acetonitrile of mass concentration 0.05%
For 1ml/min, column temperature is 31 DEG C；0.05% ammonium acetate solution and acetonitrile carries out gradient elution in the following proportions: 88%:
12%, 0-5min；50%:50%, 25-35min；88%:12%, 36-46min.
The ammonium acetate solution is using hydrochloric acid tune pH value to 9.
After sample first uses mobile phase solution predissolve, then carry out gradient elution.
Embodiment 4
A method of the related substance of Buddhist nun is replaced in measurement west difficult to understand, using HPLC analytical method, selects octadecyl
Silane group silica gel chromatographic column carries out gradient elution, flow velocity by mobile phase of ammonium acetate solution-acetonitrile of mass concentration 0.05%
For 1ml/min, column temperature is 30 DEG C；0.05% ammonium acetate solution and acetonitrile carries out gradient elution in the following proportions: 90%:
10%, 0-5min；45%:55%, 25-35min；90%:10%, 36-46min.
The ammonium acetate solution is using hydrochloric acid tune pH value to 8.5.
After sample first uses mobile phase solution predissolve, then carry out gradient elution.
In the mobile phase solution for predissolve, the volume ratio of ammonium acetate solution and acetonitrile is 30:70.
Embodiment 5
A method of the related substance of Buddhist nun is replaced in measurement west difficult to understand, using HPLC analytical method, selects octadecyl
Silane group silica gel chromatographic column carries out gradient elution, flow velocity by mobile phase of ammonium acetate solution-acetonitrile of mass concentration 0.05%
For 1.1ml/min, column temperature is 32 DEG C；Described 0.05% ammonium acetate solution and acetonitrile carries out gradient elution in the following proportions:
90%:10%, 0-5min；40%:60%, 25-35min；90%:10%, 36-46min.
The ammonium acetate solution is using hydrochloric acid tune pH value to 8.
After sample first uses mobile phase solution predissolve, then carry out gradient elution.
In the mobile phase solution for predissolve, the volume ratio of ammonium acetate solution and acetonitrile is 30:70.
Detection wavelength is 240~260nm；Sample volume is 20 μ L.
The present invention measures mobile phase and each 20 μ L of test solution respectively, under the identical chromatographic conditions of this measuring method into
Sample records chromatogram (Fig. 1).West difficult to understand is good for separating between Buddhist nun and 9 impurity peaks, and blank solvent is noiseless to measuring.
A specific embodiment of the invention above described embodiment only expresses, the description thereof is more specific and detailed, but simultaneously
Limitations on the scope of the patent of the present invention therefore cannot be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to guarantor of the invention
Protect range.
Claims (6)
1. method of the Buddhist nun in relation to substance is replaced in a kind of measurement west difficult to understand, it is characterised in that: use HPLC analytical method, select
Octadecylsilane chemically bonded silica chromatographic column carries out gradient by mobile phase of ammonium acetate solution-acetonitrile of mass concentration 0.05%
Elution, flow velocity 0.9-1.2ml/min, column temperature are 30-32 DEG C；0.05% ammonium acetate solution and acetonitrile carries out in the following proportions
Gradient elution: 85-90%:10-15%, 0-5min；40-55%:45-60%, 25-35min；85-90%:10-15%, 36-
46min。
2. method of the Buddhist nun in relation to substance is replaced in measurement according to claim 1 west difficult to understand, it is characterised in that: the ammonium acetate is molten
Liquid is using hydrochloric acid tune pH value to 8-9.
3. method of the Buddhist nun in relation to substance is replaced in measurement according to claim 1 west difficult to understand, it is characterised in that: sample first uses mobile phase
After solution predissolve, then carry out gradient elution.
4. method of the Buddhist nun in relation to substance is replaced in measurement according to claim 3 west difficult to understand, it is characterised in that: described to be used for predissolve
Mobile phase solution in, the volume ratio of ammonium acetate solution and acetonitrile is 30:70.
5. method of the Buddhist nun in relation to substance is replaced in measurement according to claim 1 west difficult to understand, it is characterised in that: Detection wavelength 240
~260nm；Sample volume is 20 μ L.
6. method of the Buddhist nun in relation to substance is replaced in measurement according to claim 1 west difficult to understand, it is characterised in that: described 0.05% vinegar
Acid ammonium solution and acetonitrile carry out gradient elution: 90%:10%, 0-5min in the following proportions；40%:60%, 25-35min；
90%:10%, 36-46min.
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| Application Number | Priority Date | Filing Date | Title |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910754094.4A CN110376309A (en) | 2019-08-15 | 2019-08-15 | A method of replacing the related substance of Buddhist nun in measurement west difficult to understand |
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| CN110376309A true CN110376309A (en) | 2019-10-25 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107192773A (en) * | 2017-05-17 | 2017-09-22 | 江苏斯威森生物医药工程研究中心有限公司 | A kind of detection is difficult to understand uncommon for Buddhist nun's content and the high-efficient liquid phase technique about material |
| CN107328871A (en) * | 2017-05-12 | 2017-11-07 | 中国医学科学院肿瘤医院 | Ao Xi replaces the drug concentration of Buddhist nun in UPLC MS/MS combinations detection human plasma and/or cerebrospinal fluid |
| CN107727773A (en) * | 2017-11-23 | 2018-02-23 | 中山奕安泰医药科技有限公司 | Using the liquid chromatography detection methanesulfonic acid uncommon method for Buddhist nun's purity difficult to understand |
| CN108017620A (en) * | 2016-10-31 | 2018-05-11 | 北京睿创康泰医药研究院有限公司 | The methanesulfonic acid uncommon preparation method for Buddhist nun's process contaminants difficult to understand |
-
2019
- 2019-08-15 CN CN201910754094.4A patent/CN110376309A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108017620A (en) * | 2016-10-31 | 2018-05-11 | 北京睿创康泰医药研究院有限公司 | The methanesulfonic acid uncommon preparation method for Buddhist nun's process contaminants difficult to understand |
| CN107328871A (en) * | 2017-05-12 | 2017-11-07 | 中国医学科学院肿瘤医院 | Ao Xi replaces the drug concentration of Buddhist nun in UPLC MS/MS combinations detection human plasma and/or cerebrospinal fluid |
| CN107192773A (en) * | 2017-05-17 | 2017-09-22 | 江苏斯威森生物医药工程研究中心有限公司 | A kind of detection is difficult to understand uncommon for Buddhist nun's content and the high-efficient liquid phase technique about material |
| CN107727773A (en) * | 2017-11-23 | 2018-02-23 | 中山奕安泰医药科技有限公司 | Using the liquid chromatography detection methanesulfonic acid uncommon method for Buddhist nun's purity difficult to understand |
Non-Patent Citations (4)
| Title |
|---|
| CHAKRADHAR T 等: "A new stability indicating RP-HPLC method for estimation of Osimertinib Mesylate", 《JOURNAL OF DRUG DELIVERY AND THERAPEUTICS》 * |
| 周平 等: "HPLC法测定甲磺酸奥希替尼的含量", 《中国药科大学学报》 * |
| 夏征农 等: "《辞海 数学•物理•化学分册》", 31 December 1987 * |
| 戴芸 等: "HPLC法测定奥斯替尼原料药的含量", 《化学工程师》 * |
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