CN104749288B - A kind of liquid phase chromatography analytical method of Parecoxib Sodium about material - Google Patents
A kind of liquid phase chromatography analytical method of Parecoxib Sodium about material Download PDFInfo
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Abstract
The invention provides a kind of liquid phase chromatography analytical method of Parecoxib Sodium about material：1 system suitability is tested：(1) reference substance of each impurity and Parecoxib Sodium is taken respectively, is diluted, as system suitability solution；(2) liquid chromatograph is set, system suitability solution is injected into liquid chromatograph, record chromatogram, until the separating degree between each peak meets regulation；2 determination experiments：(1) Parecoxib Sodium to be measured is taken in container, solubilizer dissolves and dilutes, used as need testing solution；(2) need testing solution is taken, is diluted, as contrast solution；(3) need testing solution and contrast solution injection liquid chromatograph are taken respectively, record chromatogram；(4) according to the peak in the chromatogram of need testing solution, calculate by Self-control method.Methods described can detect micro potential impurity present in Parecoxib Sodium accurately, efficiently at low cost, and provide good quality assurance, be can be additionally used in the detection and analysis of other materials in addition.
Description
Technical field
The present invention relates to a kind of analysis method, more particularly to a kind of Parecoxib Sodium is about the liquid-phase chromatographic analysis side of material
Method.
Background technology
Parecoxib Sodium (Parecoxib Sodium) is first injection cox 2 inhibitor, be can be used for postoperative middle heavy
The treatment of degree Acute Pain.Its clinical efficacy is obtained in the pain management after various surgeries such as the department of stomatology, gynaecology, orthopaedics
To confirmation, and Postoperative Intravenous give the consumption that this product can reduce morphine, and then improve the quality of Postoperative Analgesia After.
As with its unique advantage, the range of application of Parecoxib Sodium constantly expands, wherein, CN104250232 is public
A kind of preparation method of Parecoxib Sodium is opened, methods described is the Jing Guohuang for raw material with 3,4- diphenyl -5- methylisoxazoles
Change, ammonolysis, acylation, obtain Parecoxib Sodium into after salt and recrystallization, simple to operate, reproducible, high income, low cost are obtained
The single impurity of Parecoxib Sodium finished product for arriving below 0.1%, suitable industrialized production.
Although Parecoxib Sodium can have been produced on a large scale at present, with regard to the relevant material of Parecoxib Sodium
Analyzing detecting method, still relies on the research of the instrument and complexity of precision.And injection Parecoxib Sodium import registered standard
In a kind of existing analysis method, find in detection test of the Parecoxib Sodium about material, the method effectively can not divide
From some impurity, also cannot accurately and effectively these potential impurity of quantitative determination, cannot more ensure the quality of medicine.
The content of the invention
In order to solve prior art in analyzing detecting method of the Parecoxib Sodium about material, the defect for existing and disadvantage
End, reaches the purpose of potential impurity in accurate and effective, quantitative determination Parecoxib Sodium, the invention provides a kind of SC 69124
Liquid phase chromatography analytical method of the sodium about material, the method accurately and efficiently can detect micro present in Parecoxib Sodium
Potential impurity, provides good quality assurance for Parecoxib Sodium bulk drug.
Subject of the present invention is a kind of liquid phase chromatography analytical method of Parecoxib Sodium about material, it is characterised in that bag
Include：
Step 1：System suitability is tested：(1) reference substance of each impurity and Parecoxib Sodium is taken respectively, is diluted to solvent
Mixed solution, as system suitability solution；(2) liquid chromatograph is set, and the system suitability solution is injected into liquid phase
Chromatograph, records chromatogram, until separating degree between each impurity peaks and Parecoxib Sodium peak meets regulation, sets described in fixation
It is fixed；
Step 2：Determination experiment：(1) Parecoxib Sodium to be measured is taken in container, solubilizer dissolves and dilutes, as confession examination
Product solution；(2) need testing solution, solubilization dilution agent, as contrast solution are taken；(3) take respectively the need testing solution and
Contrast solution injects liquid chromatograph, records chromatogram；(4) according to the peak in the chromatogram of need testing solution, by own control
Method is calculated.
In a preferred embodiment of the invention, preferably per milliliter of the system suitability solution contains SC 69124
Sodium 1mg, each impurity are the solution of 1.5 μ g.
When using liquid chromatograph, it is preferable that injection 5 μ l of solution to be measured.
In a preferred embodiment of the invention, the need testing solution is different from the concentration of the contrast solution, excellent
Selection of land, the concentration of the need testing solution is 1mg/ml, and the concentration of the contrast solution is 1 μ g/ml.
Preferably, the solvent is acetonitrile solution, and its volume ratio is preferably acetonitrile：Water=(40:60).
The liquid phase chromatography analytical method using instrument include liquid chromatograph, Chromatographic data system and chromatogram
Post.Preferably, the chromatographic column selects 100mm × 4.6mm silicagel columns, built-in C18 Core-shell technologies to be bonded pentafluorophenyl group filler, institute
Packing material size is stated for 2.6 μm.It is further preferred that the Detection wavelength of the liquid chromatograph is 230nm, with water-methanol-trifluoro second
(volume ratio is preferably 10 for acid：90：0.05) it is mobile phase A, with water-methanol-trifluoroacetic acid, (volume ratio is preferably 90：10：
0.05) it is Mobile phase B, and according to the form below gradient elution：
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 50 | 50 |
| 8 | 50 | 50 |
| 16 | 80 | 20 |
| 20 | 80 | 20 |
| 20.1 | 50 | 50 |
| 25 | 50 | 50 |
On the other hand, it is of the invention also to include liquid phase chromatography analytical method described above in the detection and analysis of other materials
Application, including：
Step 1：System suitability is tested：(1) reference substance of each impurity and something is taken respectively, and mixing is diluted to solvent
Solution, as system suitability solution；(2) liquid chromatograph is set, and the system suitability solution is injected into liquid chromatogram
Instrument, records chromatogram, until the separating degree between each impurity peaks and something meets regulation, the fixation setting；
Step 2：Determination experiment：(1) something to be measured is taken in container, solubilizer dissolves and dilutes, molten as test sample
Liquid；(2) need testing solution, solubilization dilution agent, as contrast solution are taken；(3) need testing solution and control are taken respectively
Solution injects liquid chromatograph, records chromatogram；(4) according to the peak in the chromatogram of need testing solution, based on Self-control method
Calculate.
Liquid phase chromatography analytical method of the present invention, can be effectively and accurately potential miscellaneous in quantitative determination Parecoxib Sodium
Matter, makes the quality of Parecoxib Sodium correlation medicine be guaranteed, allows the numerous common people trust medication；And, the present invention can be with
Potential impurity in Parecoxib Sodium determined on the liquid phase instrument that commonly uses of current medicine production plant effectively, it is to avoid made
The ultrahigh-pressure liquid chromatograph generally not used with more expensive, factory, reduces testing cost, and makes detection more conventional
Change.
Specific embodiment
The invention provides a kind of liquid phase chromatography analytical method of Parecoxib Sodium about material, it is characterised in that include：
Step 1：System suitability is tested：(1) reference substance of each impurity and Parecoxib Sodium is taken respectively, is diluted to solvent
Mixed solution, as system suitability solution；(2) liquid chromatograph is set, and the system suitability solution is injected into liquid phase
Chromatograph, records chromatogram, until separating degree between each impurity peaks and Parecoxib Sodium peak meets regulation, sets described in fixation
It is fixed；
Step 2：Determination experiment：(1) Parecoxib Sodium to be measured is taken in container, solubilizer dissolves and dilutes, as confession examination
Product solution；(2) need testing solution, solubilization dilution agent, as contrast solution are taken；(3) take respectively the need testing solution and
Contrast solution injects liquid chromatograph, records chromatogram；(4) according to the peak in the chromatogram of need testing solution, by own control
Method is calculated.
Wherein, studied according to us, it is preferable that each impurity includes impurity I, impurity II, impurity III, impurity IV, miscellaneous
Matter V, impurity VI.
The system suitability solution is preferably per milliliter and contains Parecoxib Sodium 1mg, I 1.5 μ g of impurity, II 1.5 μ of impurity
G, III 1.5 μ g of impurity, IV 1.5 μ g of impurity, V 1.5 μ g of impurity, the solution of VI 1.5 μ g of impurity.
When using liquid chromatograph, 5 μ l of solution to be measured are injected.
The need testing solution is different from the concentration of the contrast solution, it is preferable that the concentration of the need testing solution is
1mg/ml, the concentration of the contrast solution is 1 μ g/ml.
Preferably, the solvent is acetonitrile solution, and its volume ratio is preferably acetonitrile：Water=(40:60).
The liquid phase chromatography analytical method using instrument include liquid chromatograph, Chromatographic data system and chromatogram
Post.Preferably, the chromatographic column selects 100mm × 4.6mm silicagel columns, built-in C18 Core-shell technologies to be bonded pentafluorophenyl group filler, institute
Packing material size is stated for 2.6 μm.It is further preferred that the Detection wavelength of the liquid chromatograph is 230nm, with water-methanol-trifluoro second
(volume ratio is preferably 10 for acid：90：0.05) it is mobile phase A, with water-methanol-trifluoroacetic acid, (volume ratio is preferably 90：10：
0.05) it is Mobile phase B, and preferably according to the form below gradient elution：
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 50 | 50 |
| 8 | 50 | 50 |
| 16 | 80 | 20 |
| 20 | 80 | 20 |
| 20.1 | 50 | 50 |
| 25 | 50 | 50 |
Present invention also offers a kind of liquid phase chromatography analytical method described above answering in the detection and analysis of other materials
With, including：
Step 1：System suitability is tested：(1) reference substance of each impurity and something is taken respectively, and mixing is diluted to solvent
Solution, as system suitability solution；(2) liquid chromatograph is set, and the system suitability solution is injected into liquid chromatogram
Instrument, records chromatogram, until the separating degree between each impurity peaks and something meets regulation, the fixation setting；
Step 2：Determination experiment：(1) something to be measured is taken in container, solubilizer dissolves and dilutes, molten as test sample
Liquid；(2) need testing solution, solubilization dilution agent, as contrast solution are taken；(3) need testing solution and control are taken respectively
Solution injects liquid chromatograph, records chromatogram；(4) according to the peak in the chromatogram of need testing solution, based on Self-control method
Calculate.
Embodiment 1：
Step 1：System suitability is tested：(1) impurity I, impurity II, impurity III, impurity IV, impurity V, impurity are taken respectively
VI and the reference substance of Parecoxib Sodium, with acetonitrile solution (volume ratio 40:60) it is diluted to per milliliter and contains Parecoxib Sodium
1mg, I 1.5 μ g of impurity, II 1.5 μ g of impurity, III 1.5 μ g of impurity, IV 1.5 μ g of impurity, V 1.5 μ g of impurity, impurity VI 1.5 μ g
Mixed solution, as system suitability solution；(2) liquid chromatograph is set, wherein, chromatographic column selects 100mm × 4.6mm silica gel
Post, built-in C18 Core-shell technologies are bonded pentafluorophenyl group filler, and described filler particle diameter is 2.6 μm, the detection ripple of the liquid chromatograph
A length of 230nm, with water-methanol-trifluoroacetic acid, (volume ratio is preferably 10：90：0.05) it is mobile phase A, with water-methanol-trifluoro
(volume ratio is preferably 90 to acetic acid：10：0.05) it is Mobile phase B, and according to the form below gradient elution：
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 50 | 50 |
| 8 | 50 | 50 |
| 16 | 80 | 20 |
| 20 | 80 | 20 |
| 20.1 | 50 | 50 |
| 25 | 50 | 50 |
, 5 μ l of the system suitability solution are injected into liquid chromatograph then, chromatogram is recorded, find each impurity peaks with
Separating degree between Parecoxib Sodium peak meets regulation, the fixation setting；
Step 2：Determination experiment：(1) take Parecoxib Sodium 100mg to be measured to be placed in 100mL measuring bottles, solubilizer dissolving is simultaneously dilute
Release to scale, as need testing solution；(2) the need testing solution 10ml is taken, solubilizer is diluted to 1 μ g/ml, it is molten as compareing
Liquid；(3) need testing solution and 5 μ l of contrast solution injection liquid chromatographs are taken respectively, record chromatogram；(4) test sample is molten
If any the peak consistent with impurity I, impurity II, impurity III, impurity IV, impurity V and VI retention time of impurity in the chromatogram of liquid,
Calculate by Self-control method.
Wherein, impurity spectrum is as follows：
Above the specific embodiment of the present invention is described in detail, but which has been intended only as example, the present invention has not been limited
It is formed on particular embodiments described above.To those skilled in the art, any equivalent modifications carried out by the present invention and
Replacement is also all among scope of the invention.Therefore, the impartial conversion made without departing from the spirit and scope of the invention and
Modification, should all cover within the scope of the invention.
Claims (6)
1. liquid phase chromatography analytical method of a kind of Parecoxib Sodium about material, it is characterised in that include：
Step 1：System suitability is tested：(1) impurity I, impurity II, impurity III, impurity IV, impurity V, VI and of impurity are taken respectively
The reference substance of Parecoxib Sodium, is diluted to mixed solution with solvent, used as system suitability solution；(2) liquid chromatograph is set,
And the system suitability solution is injected into liquid chromatograph, record chromatogram, until each impurity peaks and Parecoxib Sodium peak it
Between separating degree meet regulation, the fixation setting；
Step 2：Determination experiment：(1) Parecoxib Sodium to be measured is taken in container, solubilizer dissolves and dilutes, molten as test sample
Liquid；(2) need testing solution, solubilization dilution agent, as contrast solution are taken；(3) need testing solution and control are taken respectively
Solution injects liquid chromatograph, records chromatogram；(4) according to the peak in the chromatogram of need testing solution, based on Self-control method
Calculate；
The liquid phase chromatography analytical method using instrument include liquid chromatograph, Chromatographic data system and chromatographic column；Institute
The Detection wavelength for stating liquid chromatograph is 230nm, with water-methanol-trifluoroacetic acid as mobile phase A, with water-methanol-trifluoroacetic acid
For Mobile phase B, and carry out gradient elution；The volume ratio of the water-methanol-trifluoroacetic acid in the mobile phase A is 10：90：0.05,
The volume ratio of the water-methanol-trifluoroacetic acid in the Mobile phase B is 90：10：0.05；
Wherein, the chromatographic column selects 100mm × 4.6mm silicagel columns, built-in C18 Core-shell technologies to be bonded pentafluorophenyl group filler, institute
Packing material size is stated for 2.6 μm；
Wherein, the condition of the gradient elution is：0～8min：50% mobile phase A, 50% Mobile phase B；8～16min：50% →
80% mobile phase A, 50% → 20% Mobile phase B；16～20min：80% mobile phase A, 20% Mobile phase B；20～20.1min：
80% → 50% mobile phase A, 20% → 50% Mobile phase B；20.1～25min：50% mobile phase A, 50% Mobile phase B；
Wherein, the structural formula difference of impurity I～VI is as follows：
Impurity I：
Impurity II：
Impurity III：
Impurity IV：
Impurity V：
Impurity VI：
2. liquid phase chromatography analytical method according to claim 1, it is characterised in that the system suitability solution is preferably every
Milliliter is the solution of 1.5 μ g containing Parecoxib Sodium 1mg, each impurity.
3. liquid phase chromatography analytical method according to claim 1, it is characterised in that when using liquid chromatograph, injection is treated
Survey solution is 5 μ l.
4. liquid phase chromatography analytical method according to claim 1, it is characterised in that the concentration of the need testing solution is 1mg/
Ml, the concentration of the contrast solution is 1 μ g/ml.
5. liquid phase chromatography analytical method according to claim 1, it is characterised in that the solvent is acetonitrile solution.
6. liquid phase chromatography analytical method according to claim 5, it is characterised in that acetonitrile and water in the acetonitrile solution
Volume ratio is 40:60.
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| CN105367508B (en) * | 2015-11-25 | 2017-09-29 | 蚌埠丰原医药科技发展有限公司 | A kind of preparation method of Parecoxib Sodium synthesis technique impurity |
| CN105372376B (en) * | 2015-11-26 | 2021-04-06 | 天津药物研究院有限公司 | Detection method and application of parecoxib sodium genotoxic impurity |
| CN106908525B (en) * | 2017-01-16 | 2019-07-23 | 山东省药学科学院 | A kind of analysis method measuring SC 69124 intermediate with SC 69124 in relation to substance |
| CN107976500B (en) * | 2017-11-29 | 2021-09-28 | 浙江震元制药有限公司 | Diaryl-substituted isoxazole compound and preparation method and application thereof |
| CN110398555B (en) * | 2018-04-24 | 2022-07-22 | 重庆圣华曦药业股份有限公司 | Detection method of capecitabine related substances |
| CN108828127A (en) * | 2018-06-21 | 2018-11-16 | 上药东英（江苏）药业有限公司 | Liquid-phase chromatography method in relation to substance in a kind of detection Parecoxib Sodium and synthetic intermediate |
| CN111089931A (en) * | 2019-11-28 | 2020-05-01 | 上海秀新臣邦医药科技有限公司 | Detection method of parecoxib sodium gene genotoxicity impurity |
| CN111257441B (en) * | 2019-12-31 | 2022-07-29 | 河南润弘制药股份有限公司 | Method for detecting impurities in parecoxib sodium synthesis process |
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