CN107340350B - The measuring method of injection octreotide acetate microspheres amount - Google Patents
The measuring method of injection octreotide acetate microspheres amount Download PDFInfo
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- CN107340350B CN107340350B CN201710693134.XA CN201710693134A CN107340350B CN 107340350 B CN107340350 B CN 107340350B CN 201710693134 A CN201710693134 A CN 201710693134A CN 107340350 B CN107340350 B CN 107340350B
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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
- G01N30/60—Construction of the column
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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
- G01N30/26—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
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Abstract
The invention discloses a kind of measuring methods of injection octreotide acetate microspheres amount, using liquid chromatography, the liquid phase testing conditions are as follows: TechMate C 18-ST chromatographic column is used, with mobile phase A and Mobile phase B Isocratic clution；The mobile phase A and Mobile phase B are the mixed liquor of acetonitrile, 10% tetramethyl ammonium hydroxide solution and water.Measuring method of the invention changes chromatographic column on the basis of primary standard, selects the preferable chromatographic column of performance to elute sample, enhances the eluting power to sample；Mobile phase is changed to two-phase by original three-phase, saves resource.Reproducibility is more preferable after flow visualizing change, and precision is more preferable；After mobile phase ratio adjustment, the eluting power of principal component is greatly reinforced, sample quickly elutes, and greatlys save time and Material Cost.
Description
Technical field
The invention belongs to liquid chromatographic detection fields, and in particular to the measurement side of injection octreotide acetate microspheres amount
Method, this method derive from injection octreotide acetate microballoon import registered standard, to injection octreotide acetate microspheres amount into
Row measurement.
Background technique
Octreotide (Octreotide) is artificial synthesized octapeptide cyclic compound, four amino acid of front end and natural
Growth hormone release inhibiting hormone tetradecapeptide front-end architecture it is similar, be SMS 201-995.Octreotide microballoon is the durative action preparation of Octreotide.Note
It penetrates with octreotide acetate microballoon through buttocks muscles deep drug administration by injection, indication is that acromegalia and gastrointestinal pancreatic secretion are swollen
Tumor.
Existing injection octreotide acetate microballoon primary standard content assaying method is as follows:
Chromatographic column: being the Inertsil ODS-2,4.6 × 150mm of filler to octadecylsilane chemically bonded silica；
Mobile phase A: -10% tetramethyl ammonium hydroxide solution of acetonitrile-water (100:20:880) and with phosphorus acid for adjusting pH value extremely
2.5；
Mobile phase B: -10% tetramethyl ammonium hydroxide solution of acetonitrile-water (400:20:580) and with phosphorus acid for adjusting pH value extremely
2.5；
Mobile phase C: -10% tetramethyl ammonium hydroxide solution of acetonitrile-water (800:20:180) and with phosphorus acid for adjusting pH value extremely
2.5；
Flow velocity: 1.7ml/ minutes；
Sampling volume: 10 μ l；
Detection wavelength: 210nm；
According to following table gradient elution:
Measuring method is complex in primary standard, it is recommended to use chromatographic column be Japanese Shimadzu Corporation's early stage research and development chromatography
Column, reproducibility is poor for measurement, precision is poor, weaker to the eluting power of principal component, elution time is long.
Summary of the invention
The present inventor has been surprisingly found that in the measurement practice of injection octreotide acetate microspheres amount, uses
TechMate C18-ST chromatographic column, after being changed to two-phase by three-phase by flow phase system and adjusted mobile phase ratio, principal component peak reason
Improved by plate number, tailing factor is good, achieve it is reserved less than technical effect, the present invention is namely based on this discovery.
Injection octreotide acetate microspheres amount measuring method of the invention, specific as follows:
The measuring method of injection octreotide acetate microspheres amount, using liquid chromatography, the liquid phase testing conditions are as follows:
Using TechMate C18-ST chromatographic column, with mobile phase A and Mobile phase B Isocratic clution；The mobile phase A and Mobile phase B are equal
For acetonitrile, the mixed liquor of 10% tetramethyl ammonium hydroxide solution and water.
Preferably, the concrete model parameter of the TechMate C18-ST chromatographic column is (4.6 × 250mm, 5 μm).
Preferably, the acetonitrile of the mobile phase A: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is 50-200:
10-30:800-950, and with phosphorus acid for adjusting pH value to 2.5；The acetonitrile of the Mobile phase B: 10% tetramethyl ammonium hydroxide solution:
The volume ratio of water is 300-500:10-30:500-650, and with phosphorus acid for adjusting pH value to 2.5.
Preferably, the acetonitrile of the mobile phase A: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is 100:20:
880；The acetonitrile of the Mobile phase B: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is 400:20:580.
Preferably, the volume ratio of the mobile phase A and Mobile phase B is 50:50, and flow rate of mobile phase is 1-3ml/ minutes.
Still more preferably, the flow rate of mobile phase is 1.7ml/ minutes.
Still more preferably, the column temperature of the chromatographic column is 20-35 DEG C.
Still more preferably, the column temperature of the chromatographic column is 30 DEG C.
Still more preferably, Detection wavelength 210nm.
Still more preferably, sampling volume is 10 μ l.
Content assaying method of the invention greatly promotes the eluting power of principal component, the specificity of method, accuracy,
Precision etc. meets newest standards requirement.
The invention has the benefit that
1 changes chromatographic column on the basis of primary standard, selects the preferable chromatographic column of performance to elute sample, enhances
To the eluting power of sample.
2 mobile phases are changed to two-phase by original three-phase, save resource.Reproducibility is more preferable after flow visualizing change, accurate
Degree is more preferable.
After the adjustment of 3 mobile phase ratios, the eluting power of principal component is greatly reinforced, sample quickly elutes, when greatling save
Between and Material Cost.
Detailed description of the invention
Fig. 1 is the chromatogram of the primary standard content assaying method of injection octreotide acetate microballoon；
Fig. 2 is the chromatogram of the content assaying method of the embodiment of the present invention 3 of injection octreotide acetate microballoon.
Specific embodiment
By the technology contents that the present invention will be described in detail, construction feature, reached purpose and efficacy, hereby enumerates embodiment below
It is explained in detail.
Embodiment 1
The measuring method of injection octreotide acetate microspheres amount, using liquid chromatography, the liquid phase testing conditions are as follows:
Using TechMate C18-ST chromatographic column, with mobile phase A and Mobile phase B Isocratic clution；The mobile phase A and Mobile phase B are equal
For acetonitrile, the mixed liquor of 10% tetramethyl ammonium hydroxide solution and water.
The concrete model parameter of the TechMate C18-ST chromatographic column is (4.6 × 250mm, 5 μm).
The acetonitrile of the mobile phase A: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is 50:10；800, it is used in combination
Phosphorus acid for adjusting pH value is to 2.5；The acetonitrile of the Mobile phase B: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is 300:
10:500, and with phosphorus acid for adjusting pH value to 2.5.
The volume ratio of the mobile phase A and Mobile phase B is 50:50, and flow rate of mobile phase is 1ml/ minutes.
The column temperature of the chromatographic column is 20 DEG C.
Detection wavelength is 210nm.
Sampling volume is 10 μ l.
Embodiment 2
Difference from example 1 is that the acetonitrile of the mobile phase A: 10% tetramethyl ammonium hydroxide solution: water
Volume ratio is 200:30:950, and with phosphorus acid for adjusting pH value to 2.5；The acetonitrile of the Mobile phase B: 10% tetramethyl hydroxide
Ammonium salt solution: the volume ratio of water is 500:30:650, and with phosphorus acid for adjusting pH value to 2.5.
Flow rate of mobile phase is 3ml/ minutes.
The column temperature of the chromatographic column is 35 DEG C.
Detection wavelength is 210nm.
Sampling volume is 10 μ l.
Embodiment 3
Difference from example 1 is that the acetonitrile of the mobile phase A: 10% tetramethyl ammonium hydroxide solution: water
Volume ratio is 100:20:880；The acetonitrile of the Mobile phase B: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is
400:20:580。
Flow rate of mobile phase is 1.7ml/ minutes.
The column temperature of the chromatographic column is 30 DEG C.
Detection wavelength is 210nm.
Sampling volume is 10 μ l.
Embodiment 4
Difference from example 1 is that the acetonitrile of the mobile phase A: 10% tetramethyl ammonium hydroxide solution: water
Volume ratio is 100:20:880；The acetonitrile of the Mobile phase B: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is
400:20:580。
Flow rate of mobile phase is 1ml/ minutes.
The column temperature of the chromatographic column is 30 DEG C.
Detection wavelength is 210nm.
Sampling volume is 10 μ l.
Embodiment 5
Difference from example 1 is that the acetonitrile of the mobile phase A: 10% tetramethyl ammonium hydroxide solution: water
Volume ratio is 100:20:880；The acetonitrile of the Mobile phase B: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is
400:20:580。
Flow rate of mobile phase is 3ml/ minutes.
The column temperature of the chromatographic column is 30 DEG C.
Detection wavelength is 210nm.
Sampling volume is 10 μ l.
The comparison of the content different measuring methods of 1 injection octreotide acetate microballoon of experimental example
Assay is carried out to injection octreotide acetate microballoon in the method for embodiment 1-5, as a result such as Tables 1 and 2.Figure
1 is the chromatogram of the primary standard content assaying method of injection octreotide acetate microballoon, and Fig. 2 is injection octreotide acetate microballoon
The embodiment of the present invention 3 content assaying method chromatogram.
The content assaying method of the invention of injection octreotide acetate microballoon of the invention and primary standard assay side
Method is compared, and retention time, number of theoretical plate and tailing factor have all obtained good improvement,
The content measuring method of the injection octreotide acetate microballoon of three embodiments of the invention of table 1 compares
Find out from table 1 and in conjunction with Fig. 1, principal component can be preferably separated in embodiment 1-5, and wherein embodiment 3 is optimal.
The content measuring method of the injection octreotide acetate microballoon of 2 embodiment of the present invention 3 of table and primary standard compares
Find out that embodiment 3 is significantly better than primary standard content measuring method from table 2 and in conjunction with Fig. 1, Fig. 2.
In conclusion only the preferred embodiments of the invention, is not limited the scope of protection of the present invention with this, it is all according to the present invention
Equivalent changes and modifications made by the scope of the patents and description are all within the scope of the invention patent covers.
Claims (8)
1. the measuring method of injection octreotide acetate microspheres amount, using liquid chromatography, which is characterized in that the liquid phase color
Compose testing conditions are as follows: TechMate C18-ST chromatographic column is used, with mobile phase A and Mobile phase B Isocratic clution；The flowing
Phase A and Mobile phase B are the mixed liquor of acetonitrile, 10% tetramethyl ammonium hydroxide solution and water；The acetonitrile of the mobile phase A: 10%
Tetramethyl ammonium hydroxide solution: the volume ratio of water is 50-200:10-30:800-950, and with phosphorus acid for adjusting pH value to 2.5；
The acetonitrile of the Mobile phase B: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is 300-500:10-30:500-650,
And with phosphorus acid for adjusting pH value to 2.5；The concrete model parameter of the TechMate C18-ST chromatographic column is (4.6 × 250mm, 5 μ
M).
2. the measuring method of injection octreotide acetate microspheres amount as described in claim 1, which is characterized in that the flowing
The acetonitrile of phase A: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is 100:20:880；
The acetonitrile of the Mobile phase B: 10% tetramethyl ammonium hydroxide solution: the volume ratio of water is 400:20:580.
3. the measuring method of injection octreotide acetate microspheres amount as described in claim 1, which is characterized in that the flowing
Phase A and the volume ratio of Mobile phase B are 50:50, and flow rate of mobile phase is 1-3 ml/ minutes.
4. the measuring method of injection octreotide acetate microspheres amount as claimed in claim 3, which is characterized in that the flowing
Phase flow velocity is 1.7 ml/ minutes.
5. the measuring method of injection octreotide acetate microspheres amount as claimed in claim 4, which is characterized in that the chromatography
The column temperature of column is 20-35 DEG C.
6. the measuring method of injection octreotide acetate microspheres amount as claimed in claim 5, which is characterized in that the chromatography
The column temperature of column is 30 DEG C.
7. the measuring method of injection octreotide acetate microspheres amount as claimed in claim 6, which is characterized in that Detection wavelength
For 210nm.
8. the measuring method of injection octreotide acetate microspheres amount as claimed in claim 7, which is characterized in that sampling volume is
10μl。
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| WO2011112576A1 (en) * | 2010-03-10 | 2011-09-15 | Ambrilia Biopharma Inc. | Microspheres for sustained release of octreotide acetate |
| CN102526700B (en) * | 2011-12-31 | 2014-08-06 | 江苏奥赛康药业股份有限公司 | Octreotide acetate freeze-dried combination for injection and preparation method thereof |
| CN103932996B (en) * | 2014-05-15 | 2015-12-02 | 南京正宽医药科技有限公司 | A kind of Octreotide acetate freeze-dried combination for injection and preparation method thereof |
| CN106668830B (en) * | 2016-12-26 | 2020-04-28 | 武汉人福药业有限责任公司 | Octreotide acetate injection and preparation process thereof |
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