CN109030655A - A kind of method of quick measurement Eliquis content - Google Patents
A kind of method of quick measurement Eliquis content Download PDFInfo
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- CN109030655A CN109030655A CN201810941052.7A CN201810941052A CN109030655A CN 109030655 A CN109030655 A CN 109030655A CN 201810941052 A CN201810941052 A CN 201810941052A CN 109030655 A CN109030655 A CN 109030655A
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- eliquis
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- methanol
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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
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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
-
- 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
- G01N2030/042—Standards
- G01N2030/047—Standards external
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
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- 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 methods of quickly measurement Eliquis content, and using octadecylsilane chemically bonded silica as the chromatographic column of filler, 5mmol/L ammonium acetate solution: methanol (70:30) is mobile phase；Flow velocity is 1.0ml/min；Column temperature is 25 DEG C；Detection wavelength is 280nm, and runing time is 4 minutes；Precision measures 15 μ l of reference substance solution, injects liquid chromatograph, is detected.The present invention will greatly shorten by optimization chromatographic condition, and improve checkability, each time sample introduction analysis time, it is only necessary to 4 minutes, greatly shorten experimental period, save experimental period and cost；By optimizing mobile phase composition and ratio, main peak trailing phenomenon is reduced, and simplify mobile phase preparation procedure.
Description
Technical field
The present invention relates to a kind of methods of quickly measurement Eliquis content, belong to technical field of chemical detection.
Background technique
Apixaban tablet, main component are Eliquis (Apixaban), entitled 4,5,6, the 7- tetrahydro -1- of chemistry
(4- methoxyphenyl) -7- oxo -6- [4- (2- oxo -1- piperidyl) phenyl] -1H- azoles azoles simultaneously [3,4-C] pyridine -3- carbonyl
Amine is oral anticoagulation object, is a kind of novel Xa factor inhibitor.Its main function is to prevent and treat thrombus, for selecting a time
The prevention of hip joint or replacement knee in arthroplasty adult patient Venous Thrombosis.
But the content of the impurity of Eliquis has a great impact to the quality and drug safety of Eliquis, establishes quasi-
Really quickly the method for measurement Eliquis foreign body content is particularly important.The invention of Publication No. CN 107991412A is special
Sharp " method of high effective liquid chromatography for measuring Eliquis impurity content ".High performance liquid chromatography is used at present, measures Ah piperazine
The technology of the content of husky class's piece is primarily present following problems:
1) Check-Out Time is longer, and every needle about needs 20 minutes；
2) hangover of principal component peak is more serious, influences separating effect；
3) mobile phase needs to adjust pH value, and the error of pH value is easy to cause the drift of peak retention time when different personnel operate
It moves.
Summary of the invention
The technical problem to be solved by the present invention is to overcome the contents of liquid chromatography for measuring Eliquis in the prior art
When detection time it is longer, mobile phase needs to adjust pH value and obtains defect, provides a kind of method of quickly measurement Eliquis content.
In order to solve the above-mentioned technical problems, the present invention provides the following technical solutions:
A kind of method of quick measurement Eliquis content, comprising the following steps:
Test solution prepares: Apixaban tablet 5 taken, is set in 100ml measuring bottle, appropriate 50%~80% methanol is added,
It shakes 20~30 minutes；
Reference substance solution: taking test solution appropriate, and 50%~80 methanol is added and is configured to every 1ml containing Eliquis
0.125mg solution is as reference substance solution；
Using octadecylsilane chemically bonded silica as the chromatographic column of filler, 5mmol/L ammonium acetate solution: methanol (70:30)
For mobile phase；Flow velocity is 1.0ml/min；Column temperature is 25 DEG C；Detection wavelength is 280nm, and runing time is 4 minutes；
Precision measures 15 μ l of reference substance solution, injects liquid chromatograph, and in the first needle contrast solution 1, Eliquis peak is dragged
The tail factor should be in 0.8~1.5,6 needle contrast solutions 1, and the relative standard deviation of the peak area at Eliquis peak is not more than
1.3%, precision measures 15 μ l of test solution, injects liquid chromatograph, records chromatogram to 4 minutes, by external standard method with peak face
Product calculates, and should be the 95.0%~105.0% of labelled amount.
Further, the chromatographic column is 3.5 μm, 4.6 × 50mm chromatographic column.
The beneficial effects obtained by the present invention are as follows being: the present invention will be greatly shortened, be mentioned by optimization chromatographic condition analysis time
High checkability, each time sample introduction, it is only necessary to 4 minutes, greatly shorten experimental period, save experimental period and cost；Pass through
Optimize mobile phase composition and ratio, reduces main peak trailing phenomenon, and simplify mobile phase preparation procedure.
Detailed description of the invention
Attached drawing is used to provide further understanding of the present invention, and constitutes part of specification, with reality of the invention
It applies example to be used to explain the present invention together, not be construed as limiting the invention.In the accompanying drawings:
Fig. 1 is reference substance solution map figure.
Specific embodiment
Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings, it should be understood that preferred reality described herein
Apply example only for the purpose of illustrating and explaining the present invention and is not intended to limit the present invention.
Embodiment
A kind of method of quick measurement Eliquis content, comprising the following steps:
Test solution prepares: Apixaban tablet 5 taken, is set in 100ml measuring bottle, appropriate 50%~80% methanol is added,
It shakes 20~30 minutes；
Reference substance solution: taking test solution appropriate, and 50%~80 methanol is added and is configured to every 1ml containing Eliquis
0.125mg solution is as reference substance solution；
Using octadecylsilane chemically bonded silica as the chromatographic column of filler, chromatographic column is 3.5 μm, 4.6 × 50mm chromatographic column.
5mmol/L ammonium acetate solution: methanol (70:30) is mobile phase；Flow velocity is 1.0ml/min；Column temperature is 25 DEG C；Detection
Wavelength is 280nm, and runing time is 4 minutes；
Precision measures 15 μ l of reference substance solution, injects liquid chromatograph, and in the first needle contrast solution 1, Eliquis peak is dragged
The tail factor should be in 0.8~1.5,6 needle contrast solutions 1, and the relative standard deviation of the peak area at Eliquis peak is not more than
1.3%, precision measures 15 μ l of test solution, injects liquid chromatograph, records chromatogram to 4 minutes, by external standard method with peak face
Product calculates, and should be the 95.0%~105.0% of labelled amount.
According to the above method, using DAD detector, Eliquis peak purity in test sample is checked.
According to the above method, by 5 needle of reference substance solution continuous sample introduction, instrument precision is investigated.
According to the above method, 6 parts of sample solutions are prepared respectively, respectively sample introduction, investigate method repeatability.
According to the above method, the solution of 80% concentration, 100% concentration and 120% concentration is prepared respectively, and each strength solution is matched
Three parts are made, totally 9 points of solution；It is separately added into recipe quantity auxiliary material, and is settled to scale.Sample introduction respectively investigates accuracy.The rate of recovery is answered
For 98.0-102.0%；RSD answers≤2.0%
According to the above method, assay is carried out to 3 batch Apixaban tablets, data are as follows.
Finally, it should be noted that the foregoing is only a preferred embodiment of the present invention, it is not intended to restrict the invention,
Although the present invention is described in detail referring to the foregoing embodiments, for those skilled in the art, still may be used
To modify the technical solutions described in the foregoing embodiments or equivalent replacement of some of the technical features.
All within the spirits and principles of the present invention, any modification, equivalent replacement, improvement and so on should be included in of the invention
Within protection scope.Single replacement same type chromatographic column and the slightly behaviors such as change testing conditions, flow velocity or mobile phase ratio, all exist
In the scope of this patent.
Claims (2)
1. a kind of method of quickly measurement Eliquis content, which comprises the following steps:
Test solution prepares: taking Apixaban tablet 5, sets in 100ml measuring bottle, appropriate 50%~80% methanol is added, shakes
20~30 minutes；
Reference substance solution: taking test solution appropriate, and 50%~80 methanol is added and is configured to every 1ml 0.125mg containing Eliquis
Solution is as reference substance solution；
Using octadecylsilane chemically bonded silica as the chromatographic column of filler, 5mmol/L ammonium acetate solution: methanol (70:30) is stream
Dynamic phase；Flow velocity is 1.0ml/min；Column temperature is 25 DEG C；Detection wavelength is 280nm, and runing time is 4 minutes；
Precision measures 15 μ l of reference substance solution, injects liquid chromatograph, in the first needle contrast solution 1, the hangover of Eliquis peak because
Son should be in 0.8~1.5,6 needle contrast solutions 1, and the relative standard deviation of the peak area at Eliquis peak is not more than 1.3%, essence
Close 15 μ l of measurement test solution injects liquid chromatograph, records chromatogram to 4 minutes, by external standard method with calculated by peak area, answers
It is the 95.0%~105.0% of labelled amount.
2. the method for quickly measurement Eliquis content as described in claim 1, which is characterized in that the chromatographic column is 3.5 μ
M, 4.6 × 50mm chromatographic column.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810941052.7A CN109030655A (en) | 2018-08-17 | 2018-08-17 | A kind of method of quick measurement Eliquis content |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810941052.7A CN109030655A (en) | 2018-08-17 | 2018-08-17 | A kind of method of quick measurement Eliquis content |
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| CN109030655A true CN109030655A (en) | 2018-12-18 |
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| CN201810941052.7A Pending CN109030655A (en) | 2018-08-17 | 2018-08-17 | A kind of method of quick measurement Eliquis content |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111521707A (en) * | 2020-05-11 | 2020-08-11 | 苏州必宜生物科技有限公司 | Method for determining apixaban concentration in blood plasma by LC-MS/MS |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104316637A (en) * | 2014-10-30 | 2015-01-28 | 江苏宝众宝达药业有限公司 | Method for determining apixaban cleaning residues by high performance liquid chromatography |
| CN107703234A (en) * | 2017-11-30 | 2018-02-16 | 江苏宝众宝达药业有限公司 | Headspace GC determines Eliquis residual solvent method |
| US10040793B2 (en) * | 2014-10-15 | 2018-08-07 | F.I.S. Fabbrica Italiana Sintetici S.P.A. | Key intermediates and impurities of the synthesis of Apixaban: Apixaban glycol esters |
-
2018
- 2018-08-17 CN CN201810941052.7A patent/CN109030655A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10040793B2 (en) * | 2014-10-15 | 2018-08-07 | F.I.S. Fabbrica Italiana Sintetici S.P.A. | Key intermediates and impurities of the synthesis of Apixaban: Apixaban glycol esters |
| CN104316637A (en) * | 2014-10-30 | 2015-01-28 | 江苏宝众宝达药业有限公司 | Method for determining apixaban cleaning residues by high performance liquid chromatography |
| CN107703234A (en) * | 2017-11-30 | 2018-02-16 | 江苏宝众宝达药业有限公司 | Headspace GC determines Eliquis residual solvent method |
Non-Patent Citations (3)
| Title |
|---|
| SEBASTIAN BOEHR等: "Development of an UHPLC-UV-Method for Quantification of Direct Oral Anticoagulants: Apixaban, Rivaroxaban,Dabigatran, and its Prodrug Dabigatran Etexilate in Human Serum", 《THERAPEUTIC DRUG MONITORING》 * |
| 张震 等: "HPLC法测定阿哌沙班中的有关物质", 《天津药学》 * |
| 聂忠莉等: "阿哌沙班片的制备工艺与质量标准研究", 《中国新药杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111521707A (en) * | 2020-05-11 | 2020-08-11 | 苏州必宜生物科技有限公司 | Method for determining apixaban concentration in blood plasma by LC-MS/MS |
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Application publication date: 20181218 |