CN106908525A - A kind of analysis method for determining SC 69124 intermediate and SC 69124 about material - Google Patents
A kind of analysis method for determining SC 69124 intermediate and SC 69124 about material Download PDFInfo
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- CN106908525A CN106908525A CN201710027510.1A CN201710027510A CN106908525A CN 106908525 A CN106908525 A CN 106908525A CN 201710027510 A CN201710027510 A CN 201710027510A CN 106908525 A CN106908525 A CN 106908525A
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Abstract
A kind of analysis method for determining SC 69124 intermediate and SC 69124 about material, it is characterized in that using high performance liquid chromatography, with acetonitrile water mixed solution sample dissolution, with acetonitrile and acetate buffer as mobile phase, gradient elution is carried out in the chromatographic column of α acidoglycoprotein bonded silica gels.This method can effectively determine the relevant material in SC 69124 intermediate and SC 69124, SC 69124 intermediate, SC 69124 and its isomers, side reaction product, catabolite etc. under same chromatographic condition is especially realized to separate, more efficient within a short period of time separation simultaneously identifies the related impurities of SC 69124 intermediate and SC 69124, for the quality control of SC 69124 provides more reliable foundation.
Description
Technical field
The invention belongs to Pharmaceutical Analysis technical field, it is related to a kind of determine the relevant of SC 69124 intermediate and SC 69124
The analysis method of material, particularly with a kind of high performance liquid chromatography simultaneously to SC 69124 intermediate and the isomery of SC 69124
The method that body, side reaction product and catabolite are measured.
Background technology
SC 69124 intermediate 4- (5- methyl -3- phenyl -4- isoxazolyls) benzsulfamides (FD) and SC 69124 are
Specific C OX-2 inhibitor, SC 69124 is the pro-drug of FD, and both come under the former times dry goods analgesia in anti-arthritic
Medicine.Clinically SC 69124 is sold as the short medicine of postoperative pain in European market at present, after intermediate FD is because of listing
Interests/Hazard ratio is unsatisfactory and is withdrawn from from American market.Both synthetic routes are similar, it is contemplated that the risk of FD, set up exclusive
Strong, the sensitive reliable analysis method of property is controlled to the relevant material (being shown in Table 1) of FD and SC 69124, to the matter of SC 69124
Amount control is of great significance.
The content of the invention
SC 69124 intermediate 4- (5- methyl -3- phenyl -4- isoxazolyls) is determined it is an object of the invention to provide one kind
The high-efficient liquid phase color of the isomers, side reaction product and catabolite that are produced in benzsulfamide and SC 69124 synthesis route
Spectral analysis method, can be used for the study on the synthesis of SC 69124 and production process quality control.
To achieve the above object, the technical scheme is that：
One kind determine SC 69124 intermediate (FD) with SC 69124 about material analysis method, using high-efficient liquid phase color
Spectrometry, with acetonitrile-water mixed solution sample dissolution, from the chiral chromatographic column of acid seromucoid bonded silica gel, with acetonitrile-vinegar
Phthalate buffer carries out gradient elution for mobile phase.
The SC 69124 intermediate (FD) is 4- (5- methyl -3- phenyl -4- isoxazolyls) benzsulfamide, and the handkerchief is auspicious
Former times cloth is N- [[4- (5- methyl -3- phenyl -4- isoxazolyls) phenyl] sulfonyl] propionamide, and relevant material is impurity A, impurity
B, impurity C, impurity D, impurity E, impurity F and impurity G (being shown in Table 1).
The SC 69124 of table 1, FD and its relevant structure of matter formula
The eluent gradient elution program is shown in Table 2.
The eluent gradient elution program of table 2
It is 40 with volume ratio in methods described:60 acetonitrile-water mixed solution sample dissolution, is made analytical solution.
Described chromatographic column is CHIRALPAK AGP, 4mm × 100mm, 5 μm.
The flowing phase composition is acetonitrile-ammonium acetate buffer, and wherein ammonium acetate buffer concentration is 0.01mol/L, pH
4.0。
Chromatographic condition includes：Detection wavelength is 215nm；Mobile phase elution rate is 0.7mL/min；Chromatogram column temperature is 25
℃；Sample injection volume is 10 μ L.
The beneficial effects of the invention are as follows：Can effectively determine what is produced in SC 69124 synthesis route within a short period of time
Isomers, side reaction product and degradation impurity, have saved the time, reduce testing cost, can be used for SC 69124 study on the synthesis
With the quality control of production process, the quality of Related product is set to be guaranteed.
Brief description of the drawings
Reference substance liquid chromatogram after the deduction blank operation of Fig. 1 embodiments 1.
Reference substance liquid chromatogram after the deduction blank operation of Fig. 2 embodiments 2.
Test sample liquid chromatogram after the deduction blank operation of Fig. 3 embodiments 2.
In figure：1- SC 69124s；2-FD；3- impurity As；4- impurity Bs；5- impurity C；6- impurity D；7- impurity Es；8- impurity Fs；
9- impurity G.
Specific embodiment
Technical scheme is further described below in conjunction with specific embodiment, the embodiment for providing is only for illustrating this
Invention, rather than in order to limit the scope of the present invention.
This experimental evidence chromatographic column operation instructions are recommended, and prioritizing selection isopropanol system, acetonitrile system carry out investigation examination
Test.On the basis of the consideration chromatographic column durability for using, the Detection wavelength for determining composition, determine to use acetonitrile system.In second
Each chromatographic peak peak shape is poor after finding sample introduction after being tested in nitrile system, and separating degree is bad, therefore considers to add buffer salt, after experiment
Preferably 0.01mol/L ammonium acetate solutions.
Embodiment 1
(1) instrument and chromatographic condition
High performance liquid chromatograph：The highly effective liquid phase chromatographic systems of Agilent 1260 and work station.
Chromatographic column：Acid seromucoid chromatographic column (CHIRALPAK AGP, 4mm × 100mm, 5 μm).
The ammonium acetate solution of 0.01mol/L is prepared, is water phase, acetonitrile-water phase in mobile phase with vinegar acid for adjusting pH value to 6.0
Ratio carries out gradient elution by table 3, and setting flow velocity is 0.6mL/min, and Detection wavelength is 215nm, and column temperature is 25 DEG C.
Table 3
(2) experimental procedure
SC 69124, FD, impurity A, B, C, D, E, F, G reference substance are taken respectively appropriate, with acetonitrile-water (40:60) dissolve simultaneously
Dilution contains SC 69124, FD, the mixed solution of the μ g of each impurity about 2 in being made every 1mL, used as reference substance solution.Pa Rui is taken respectively
Former times cloth sample, FD samples, impurity A, B, C, D, E, F, appropriate G, with method prepare per in 1mL containing about SC 69124, FD 0.5mg and
The mixed solution of other each impurity 2 μ g, as need testing solution.
(3) assay method and result
The μ L of above-mentioned solution 10 are taken by (1) chromatographic condition sample introduction, 46min is run, chromatogram is recorded, SC 69124, FD is investigated
With the separating degree between each impurity, each impurity.Result shows that each impurity separating degree is good (see Fig. 1) in reference substance solution, but supplies
SC 69124 chromatographic peak splits point in test sample solution, influences impurity to be separated with main peak when relevant material is determined in SC 69124
Degree.Further optimize chromatographic condition such as embodiment 2.
Embodiment 2
(1) instrument and chromatographic condition
High performance liquid chromatograph：The highly effective liquid phase chromatographic systems of Agilent 1260 and work station.
Chromatographic column：Acid seromucoid chromatographic column (CHIRALPAK AGP, 4mm × 100mm, 5 μm).
The ammonium acetate solution of 0.01mol/L is prepared, is water phase, acetonitrile-water phase in mobile phase with vinegar acid for adjusting pH value to 4.0
Ratio carries out gradient elution by table 4, and setting flow velocity is 0.7mL/min, and Detection wavelength is 215nm, and column temperature is 25 DEG C.
Table 4
(2) experimental procedure
SC 69124, FD, impurity A, B, C, D, E, F, G reference substance are taken respectively appropriate, with acetonitrile-water (40:60) dissolve simultaneously
Dilution contains SC 69124, FD, the mixed solution of the μ g of each impurity about 2 in being made every 1mL, used as reference substance solution.Pa Rui is taken respectively
Former times cloth sample, FD samples, impurity A, B, C, D, E, F, appropriate G, with method prepare per in 1mL containing about SC 69124, FD 0.5mg and
The mixed solution of other each impurity 2 μ g, as need testing solution.
(3) assay method and result
The μ L of above-mentioned solution 10 are taken by (1) chromatographic condition sample introduction, 42min is run, chromatogram is recorded, investigate SC 69124, in
Separating degree between mesosome, each impurity.Result shows that each impurity separating degree of reference substance solution is good (see Fig. 2), need testing solution
In separating degree is good between each impurity and principal component, each composition chromatographic peak peak shape is good (see Fig. 3).
Claims (5)
1. a kind of analysis method for determining SC 69124 intermediate (FD) and SC 69124 about material, it is characterized in that, using height
Effect liquid phase chromatogram method, with acetonitrile-water mixed solution sample dissolution, from the chiral chromatographic column of acid seromucoid bonded silica gel,
Gradient elution is carried out by mobile phase of acetonitrile-acetate buffer；
The SC 69124 intermediate (FD) is 4- (5- methyl -3- phenyl -4- isoxazolyls) benzsulfamide, the SC 69124
It is N- [[4- (5- methyl -3- phenyl -4- isoxazolyls) phenyl] sulfonyl] propionamide, relevant material is impurity A, impurity B, miscellaneous
Matter C, impurity D, impurity E, impurity F and impurity G：
The eluent gradient elution program is：
2. in analysis method as claimed in claim 1, it is characterized in that, it is 40 with volume ratio:60 acetonitrile-water mixed solution is molten
Solution sample.
3. in analysis method as claimed in claim 1, it is characterized in that, described chromatographic column for CHIRALPAK AGP, 4mm ×
100mm, 5 μm.
4. in analysis method as claimed in claim 1, it is characterized in that, described acetonitrile-ammonium acetate buffer, wherein ammonium acetate
Buffer concentration is 0.01mol/L, pH 4.0.
5. in analysis method as claimed in claim 1, it is characterized in that, chromatographic condition includes：Detection wavelength is 215nm, flowing
Phase elution rate is 0.7mL/min, and chromatogram column temperature is 25 DEG C, and sample injection volume is 10 μ L.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108164521A (en) * | 2018-03-02 | 2018-06-15 | 成都新恒创药业有限公司 | A kind of Parecoxib Sodium degradation impurity and its preparation, detection method and application |
| 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 |
| CN114441666A (en) * | 2020-11-05 | 2022-05-06 | 成都百裕制药股份有限公司 | Method for detecting impurities in 4- (5-methyl-3-phenyl-4-isoxazole) benzenesulfonyl chloride |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108164521A (en) * | 2018-03-02 | 2018-06-15 | 成都新恒创药业有限公司 | A kind of Parecoxib Sodium degradation impurity and its preparation, detection method and application |
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| 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 |
| CN114441666A (en) * | 2020-11-05 | 2022-05-06 | 成都百裕制药股份有限公司 | Method for detecting impurities in 4- (5-methyl-3-phenyl-4-isoxazole) benzenesulfonyl chloride |
| CN114441666B (en) * | 2020-11-05 | 2024-02-27 | 成都百裕制药股份有限公司 | Method for detecting impurities in 4- (5-methyl-3-phenyl-4-isoxazole) benzenesulfonyl chloride |
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