CN108828127A - Liquid-phase chromatography method in relation to substance in a kind of detection Parecoxib Sodium and synthetic intermediate - Google Patents
Liquid-phase chromatography method in relation to substance in a kind of detection Parecoxib Sodium and synthetic intermediate Download PDFInfo
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Abstract
The invention discloses the liquid-phase chromatography methods in relation to substance in a kind of detection Parecoxib Sodium and synthetic intermediate.The present invention uses reversed-phased high performace liquid chromatographic, using pentafluorophenyl group bonded silica gel and octadecylsilane chemically bonded silica as chromatographic column filler, using UV detector, the mobile phase containing potassium dihydrogen phosphate is selected to be eluted, it is divided into the related substance measured in Parecoxib Sodium intermediate Valdecoxib and SC 69124 twice, i.e., related substance I and related substance II；Measure the mixed solution that the mobile phase in relation to substance I and in relation to substance II is methanol and potassium dihydrogen phosphate aqueous solution.The present invention is combined using two kinds of gradient methods of liquid phase phase chromatography and the related substance of 11 kinds of Parecoxib Sodiums and its intermediate is completed while being detected, and which includes 5 kinds of position isomer impurity of more difficult separation, and method high sensitivity is reproducible, and precision is high.
Description
Technical field
The invention belongs to medicine analysis fields, and in particular to be liquid chromatogram while detecting Parecoxib Sodium and its synthesis
The detection method of kind of the position isomer of 12 kinds of related substances, especially 5 in intermediate.
Background technique
The mechanism of action of non-steroidal anti-inflammatory drugs (NSAID) is by inhibiting the activity of cyclo-oxygenase (COX) to inhibit forefront
Parathyrine synthesis, thus play it is anti-inflammatory, bring down a fever and analgesic effect.Common non-steroidal anti-inflammatory agent inhibits the COX-1 of constitutive expression, together
When inhibit that inflammation is relevant or the COX-2 of induction type.Prostaglandin needed for COX-1 can be catalyzed generation normal cell function, because
And COX-1 can be inhibited so as to cause certain toxic side effects using routine NSAID.Unlike this, if drug being capable of selective depression
COX-2 and do not inhibit COX-1 substantially, then can obtain it is anti-inflammatory, bring down a fever, ease pain and other useful therapeutic effects, reduce simultaneously
Or eliminate the toxic side effect.Therefore, it is a much progress in the art that selective COX-2-2, which inhibits drug,.
Parecoxib Sodium (Parecoxib Sodium) is the Water-soluble precursor that selective COX-2-2 inhibits drug Valdecoxib
Drug is first injection cox 2 inhibitor.Parecoxib Sodium, through liver enzyme hydrolysis, converts rapidly after intravenous or intramuscular injection
To there is the substance Valdecoxib of pharmacological activity.SC 69124 can be used for the treatment of postoperative middle severe acute pain.Its clinic is treated
Effect is confirmed in the pain management after a variety of surgeries such as the department of stomatology, gynaecology, orthopaedics, and Postoperative Intravenous gives this
Product can reduce the dosage of morphine, and then improve the quality of Postoperative Analgesia After.The chemical name of Parecoxib Sodium is N- [[4- (5- first
Base -3- phenyl -4- isoxazolyl) phenyl] sulfonyl] propionamide sodium salt, structural formula sees below：
Although can produce Parecoxib Sodium, analysis detection of the Parecoxib Sodium in relation to substance on a large scale at present
Method is not included yet in pharmacopoeia of each country, and is primarily upon Parecoxib Sodium in injection Parecoxib Sodium import registered standard
Degradation impurity can not efficiently separate some process impurities in bulk pharmaceutical chemicals and bulk pharmaceutical chemicals synthetic intermediate, and it is even more impossible to accurately fixed
Amount detects these impurity, so the quality of bulk pharmaceutical chemicals and formulation products can not be effectively ensured.Through retrieving, it is directed to SC 69124 at present
The related patents (such as CN201510181846.4) of sodium Related substance method are even if can effectively divide some processes impurity
From quantitative, but the control of the position isomer for generating in synthesis process is not enough.
The present invention can efficiently separate potential 12 related substances in Parecoxib Sodium synthesis process, especially to synthesizing
5 position isomers present in journey have stronger separating capacity.
Summary of the invention
Goal of the invention：In order to solve the deficiencies in the prior art, the present invention provides a kind of detection Parecoxib Sodium and synthesis
In relation to the liquid-phase chromatography method of substance in intermediate.
Technical solution：Liquid-phase chromatography method in relation to substance in a kind of detection Parecoxib Sodium and synthetic intermediate, including
Following steps：
Step 1：System suitability experiment：(1) reference substance for taking each impurity and Parecoxib Sodium respectively is with methanol dilution
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 the separating degree between each impurity peaks and Parecoxib Sodium peak meets regulation；
Step 2：Measurement experiment：(1) it takes Parecoxib Sodium to be measured in container, methanol is added to dissolve and dilute, as examination
Product solution；(2) each impurity is taken, adds methanol dilution, as contrast solution；(3) test solution and control are taken respectively
Solution injects liquid chromatograph, records chromatogram；(4) according to the peak in the chromatogram of contrast solution and test solution, by outer
Mark method calculates.
As optimization：The system suitability solution is 0.75 containing Parecoxib Sodium 0.5mg, each impurity for every milliliter
The solution of μ g.
As optimization：When using liquid chromatograph, injecting solution to be measured is 10 μ l.
As optimization：The concentration of the test solution is 0.5mg/ml, and the concentration of the contrast solution is 0.75 μ g/
ml。
As optimization：The solvent is methanol.
As optimization：The instrument that the liquid phase chromatography analytical method uses includes liquid chromatograph, chromatographic data processing
System and chromatographic column.
As optimization：The chromatographic column selects 250mm × 4.6mm silicagel column, built-in pentafluorophenyl group bonded silica gel and ten
Eight alkyl silane bonded silica gel fillers, the packing material size are 5 μm.
As optimization：The Detection wavelength of the liquid chromatograph is 215nm, with 0.01mol/l KH2PO4Buffer is
Mobile phase A using methanol as Mobile phase B, and carries out gradient elution, and wherein pH of buffer range is 2.5~3.5.
The liquid-phase chromatography method in relation to substance is in other objects in detection Parecoxib Sodium and synthetic intermediate described in a kind of
Application in the detection and analysis of matter：
Step 1：System suitability experiment：(1) reference substance of each impurity and something is taken respectively, is that mixing is molten with methanol
Liquid, as system suitability solution；(2) liquid chromatograph is set, and the system suitability solution is injected into liquid chromatograph,
Chromatogram is recorded, until the separating degree between each impurity peaks and something meets regulation, the fixed setting；
Step 2：Measurement experiment：(1) take something to be measured in container, solubilizer is dissolved and diluted, molten as test sample
Liquid；(2) take each single impurity appropriate, solubilization dilution agent, as contrast solution；(3) take respectively the test solution and
Contrast solution injects liquid chromatograph, records chromatogram；(4) according to the peak in the chromatogram of test solution, based on external standard method
It calculates.
Beneficial effect：Specific advantage of the invention is as follows：
1, the present invention uses reversed-phased high performace liquid chromatographic, with pentafluorophenyl group bonded silica gel and octadecylsilane bonded silica
Glue is chromatographic column filler, using UV detector, selects the mobile phase containing potassium dihydrogen phosphate to be eluted, is divided into and measuring twice
Related substance in Parecoxib Sodium intermediate Valdecoxib and SC 69124, i.e., related substance I and related substance II；Measurement institute
State the mixed solution that the mobile phase in relation to substance I and in relation to substance II is methanol and potassium dihydrogen phosphate aqueous solution.
2, the present invention is combined using two kinds of gradient methods of liquid phase phase chromatography to 11 kinds of Parecoxib Sodiums and its intermediate
Related substance is completed while being detected, and which includes 5 kinds of position isomer impurity of more difficult separation, method high sensitivity, weights
Renaturation is good, and precision is high.
3, the method for the present invention catabolite Valdecoxib, work suitable for Parecoxib Sodium intermediate, bulk pharmaceutical chemicals and preparation
The detection of skill impurity and title intermediate position isomer can help more effectively to control Parecoxib Sodium quality.
Detailed description of the invention
Fig. 1 is that each impurity peaks of system suitability solution separate situation schematic diagram under the conditions of related substance I in the present invention；
Fig. 2 is that each impurity peaks of system suitability solution separate situation schematic diagram under the conditions of related substance II in the present invention.
Specific embodiment
The technical scheme in the embodiments of the invention will be clearly and completely described below, so that the technology of this field
Personnel can better understand advantages and features of the invention, to make apparent boundary to protection scope of the present invention
It is fixed.Embodiment described in the invention is only a part of the embodiment of the present invention, instead of all the embodiments, based on the present invention
In embodiment, those of ordinary skill in the art's every other implementation obtained without making creative work
Example, shall fall within the protection scope of the present invention.
Embodiment
The present invention uses reversed-phased high performace liquid chromatographic, with pentafluorophenyl group bonded silica gel and octadecylsilane chemically bonded silica
It selects the mobile phase containing potassium dihydrogen phosphate to be eluted using UV detector for chromatographic column filler, is divided into and measures pa twice
Related substance in auspicious former times cloth sodium intermediate Valdecoxib and SC 69124, i.e., related substance I and related substance II；Described in measurement
Mobile phase in relation to substance I and in relation to substance II is the mixed solution of methanol and potassium dihydrogen phosphate aqueous solution.
The related substance of Parecoxib Sodium intermediate is seen below：
The method of position isomer in a kind of detection Parecoxib Sodium synthetic intermediate of the present invention, including walk as follows
Suddenly：
1. in relation to substance I
1.1 chromatographic condition
Chromatographic column：Pentafluorophenyl group bonded silica gel is chromatographic column (the preferably Thermo Hypersil GOLD PFP of filler
4.6*250mm 5um)
Mobile phase A：0.01mol/l KH2PO4Buffer (pH2.5~3.5, preferably pH3.0)
Mobile phase B：Methanol
Gradient is as follows：
| Time (min) | A (%) | B (%) |
| 0 | 55 | 45 |
| 20 | 55 | 45 |
| 49 | 20 | 80 |
| 49.1 | 55 | 80 |
| 55 | 55 | 45 |
Column temperature：30~40 DEG C (preferably 35 DEG C)
Flow velocity：0.5~1.5ml/min (preferably 1.0ml/min)
Detection wavelength：210~220nm (preferably 215nm)
Sample volume：2~20 μ l (preferably 10 μ l)
Solvent：Methanol
The measurement of 1.2 samples
External standard method is used, the specific steps are that：
1.2.1 test solution：Precision weighs Parecoxib Sodium, and (about 25mg is set in 50ml measuring bottle, appropriate solubilizer, ultrasound
Make to dissolve, cooling, solubilizer is diluted to scale, shake up to get.SC 69124 na concn is about：0.5mg/ml.
1.2.2 impurity mother liquor：Precision weigh impurity IM9, IM10, IM11, IM2, IM2-1, IM2-2, IM2-3, IM2-4,
Respectively about 10mg is set in 20ml measuring bottle by IM3-1, IM3-2, IM3-3 and IM3-4, and solubilizer is diluted to scale, shakes up.Pipette 1ml in
In 20ml measuring bottle, solubilizer is diluted to scale to obtain the final product.(IM11,IM2,IM2-1,IM2-2,IM2-3,IM2-4,IM3-1,IM3-
2, IM3-3 and IM3-4 concentration is about：25μg/ml).
1.2.3 system suitability solution：Precision weighs Parecoxib Sodium about 25mg and sets in 50ml measuring bottle, is separately added into " 2.2
Compare mother liquor under contrast solution item " 1.5ml, then solubilizer is diluted to scale, shake up to get.(SC 69124 na concn is about：
0.5mg/ml, IM11, IM2, IM2-1, IM2-2, IM2-3, IM2-4, IM3-1, IM3-2, IM3-3 and IM3-4 concentration is about：It is dense
Degree is about 0.75ug/ml), system suitability solution map is shown in attached drawing 1.
2.1.4 contrast solution：Precision weigh impurity IM2, IM2-1, IM2-2, IM2-3, IM2-4, IM3-1, IM3-2,
Respectively about 10mg is set in 20ml measuring bottle IM3-3 and IM3-4, and solubilizer is diluted to scale, shakes up.1ml is pipetted in 20ml measuring bottle, is added
Solvent is diluted to scale, shakes up.1.5ml is pipetted in 50ml measuring bottle, solubilizer is diluted to scale to obtain the final product.(IM9 and IM10 concentration
About：0.75μg/ml).
2 in relation to substance II
2.1 chromatographic condition
Chromatographic column：Octadecylsilane chemically bonded silica is filler chromatographic column (preferably Thermo Hypersil GOLD aQ
4.6*250mm 5um)
Mobile phase A：0.01mol/l KH2PO4Buffer (pH2.5~3.5, preferably pH3.0)
Mobile phase B：Methanol
Gradient is as follows：
| Time (min) | A (%) | B (%) |
| 0 | 65 | 35 |
| 20 | 20 | 80 |
| 25 | 20 | 80 |
| 25.1 | 65 | 35 |
| 30 | 65 | 35 |
Column temperature：30~40 DEG C (preferably 35 DEG C)
Flow velocity：0.5~1.5ml/min (preferably 1.0ml/min)
Detection wavelength：210~220nm (preferably 215nm)
Sample volume：2~20 μ l (preferably 10 μ l)
Solvent：Methanol
2.1.1 test solution：Precision weigh API (about 25mg is set in 50ml measuring bottle, appropriate solubilizer, and ultrasound makes to dissolve,
Cooling, solubilizer is diluted to scale, shake up to get.(API concentration is about：0.5mg/ml).
2.1.2 impurity mother liquor：Precision weigh impurity IM9, IM10, IM11, IM2, IM2-1, IM2-2, IM2-3, IM2-4,
Respectively about 10mg is set in 20ml measuring bottle by IM3-1, IM3-2, IM3-3 and IM3-4, and solubilizer is diluted to scale, shakes up.Pipette 5ml in
In 100ml measuring bottle, solubilizer is diluted to scale to obtain the final product.(IM11,IM2,IM2-1,IM2-2,IM2-3,IM2-4,IM3-1,IM3-
2, IM3-3 and IM3-4 concentration is about：25μg/ml).
2.1.3 system suitability solution：Precision weighs API about 25mg and sets in 50ml measuring bottle, be separately added into " 2.2 control it is molten
Compare mother liquor under liquid item " 1.5ml, then solubilizer is diluted to scale, shake up to get.(API concentration is about：0.5mg/ml, IM9 and
IM10 concentration is about：Concentration is about 0.75ug/ml), system suitability map is shown in attached drawing 2.
2.1.4 contrast solution：Precision weighs impurity IM9, IM10 and IM11, and respectively about 10mg is set in same 20ml measuring bottle, solubilization
Dilution agent shakes up to scale.1ml is pipetted in 20ml measuring bottle, solubilizer is diluted to scale, shakes up.1.5ml is pipetted in 50ml amount
In bottle, solubilizer is diluted to scale to obtain the final product.(IM9 and IM10 concentration is about：0.75μg/ml).
Wherein go out peak position coincidence in relation to impurity IM9 in substance method I and intermediate compound I M2, impurity IM10 and SC 69124,
Therefore related substance method I is used for Parecoxib Sodium related substance IM2-1, IM2-2, IM2-3, IM3-1, IM3-2, IM3-3 and position
Set the detection of isomers IM2-4 and IM3-4；Impurity IM2-4 goes out peak position with intermediate compound I M2 and is overlapped in method II, therefore related object
Matter method II is used for detection of the Parecoxib Sodium in relation to substance IM9, IM10, IM11.
Parecoxib Sodium synthetic intermediate of the invention and its detection of related substance are as follows：
Instrument and chromatographic condition：
Using Thermo U3000 high performance liquid chromatograph, with pentafluorophenyl group bonded silica gel (Thermo Hypersil
GOLD PFP 4.6*250mm/5um) and octadecylsilane chemically bonded silica be filler (Thermo Hypersil GOLD aQ
4.6*250mm/5um), column temperature is 30 DEG C；Flow velocity is 1.0ml/min；Detection wavelength is 215nm.
In relation to substance I using the potassium dihydrogen phosphate aqueous solution of 0.01mol/l as mobile phase A；Using methanol as Mobile phase B；
According to the form below carries out gradient elution：
| Time (min) | A (%) | B (%) |
| 0 | 55 | 45 |
| 20 | 55 | 45 |
| 49 | 20 | 80 |
| 49.1 | 55 | 80 |
| 55 | 55 | 45 |
Precision measures system suitability solution and each 10 μ l of test solution, is injected separately into liquid chromatograph, records chromatography
Figure；
In relation to substance II using the potassium dihydrogen phosphate aqueous solution of 0.01mol/l as mobile phase A；Using methanol as Mobile phase B；
According to the form below carries out gradient elution：
| Time (min) | A (%) | B (%) |
| 0 | 65 | 35 |
| 20 | 20 | 80 |
| 25 | 20 | 80 |
| 25.1 | 65 | 35 |
| 30 | 65 | 35 |
Precision measures system suitability solution, test solution and each 10 μ l of contrast solution, is injected separately into liquid chromatograph,
Record chromatogram；
Experimental procedure：
It takes Parecoxib Sodium appropriate, the solution being made in every 1ml containing about 0.5mg is dissolved and diluted with methanol, as examination
Product solution；It is appropriate that precision measures test solution.
Another accurately weighed Parecoxib Sodium, Valdecoxib, impurity IM2-1, IM2-2, IM2-3, IM2-4, IM9, IM11,
IM3-1, IM3-2, IM3-3, IM3-4 and IM10 reference substance are each appropriate, are dissolved and are diluted with methanol the auspicious former times containing pa in every 1ml is made
The solution of cloth sodium about 0.5mg, about 0.75 μ g, as system suitability solution.
Wherein impurity IM9 and intermediate compound I M2 in method I, impurity IM10 and SC 69124 go out peak position coincidence；In method II
Impurity IM2-4 goes out peak position with intermediate compound I M2 and is overlapped.By the detection to sulfonylation sample, confirm main in reaction process
Wanting impurity is IM2-4, and no IM9 impurity generates.Therefore control, intermediate and finished product detection use related substance method I in reaction.
Claims (9)
1. the liquid-phase chromatography method in relation to substance in a kind of detection Parecoxib Sodium and synthetic intermediate, it is characterised in that：Including
Following steps：
Step 1：System suitability experiment：(1) reference substance of each impurity and Parecoxib Sodium is taken respectively, is mixing with methanol dilution
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 Parecoxib Sodium peak meets regulation；
Step 2：Measurement experiment：(1) it takes Parecoxib Sodium to be measured in container, methanol is added to dissolve and dilute, it is molten as test sample
Liquid；(2) each impurity is taken, adds methanol dilution, as contrast solution；(3) test solution and contrast solution are taken respectively
Liquid chromatograph is injected, chromatogram is recorded；(4) according to the peak in the chromatogram of contrast solution and test solution, by external standard method
It calculates.
2. the liquid-phase chromatography method in relation to substance in detection Parecoxib Sodium according to claim 1 and synthetic intermediate,
It is characterized in that：The system suitability solution is the molten of 0.75 μ g containing Parecoxib Sodium 0.5mg, each impurity for every milliliter
Liquid.
3. the liquid-phase chromatography method in relation to substance in detection Parecoxib Sodium according to claim 1 and synthetic intermediate,
It is characterized in that：When using liquid chromatograph, injecting solution to be measured is 10 μ l.
4. the liquid-phase chromatography method in relation to substance in detection Parecoxib Sodium according to claim 1 and synthetic intermediate,
It is characterized in that：The concentration of the test solution is 0.5mg/ml, and the concentration of the contrast solution is 0.75 μ g/ml.
5. the liquid-phase chromatography method in relation to substance in detection Parecoxib Sodium according to claim 1 and synthetic intermediate,
It is characterized in that：The solvent is methanol.
6. the liquid-phase chromatography method in relation to substance in detection Parecoxib Sodium according to claim 1 and synthetic intermediate,
It is characterized in that：The instrument that the liquid phase chromatography analytical method uses include liquid chromatograph, Chromatographic data system with
Chromatographic column.
7. the liquid-phase chromatography method in relation to substance in detection Parecoxib Sodium according to claim 6 and synthetic intermediate,
It is characterized in that：The chromatographic column selects 250mm × 4.6mm silicagel column, built-in pentafluorophenyl group bonded silica gel and octadecyl
Silane group silica filler, the packing material size are 5 μm.
8. the liquid-phase chromatography method in relation to substance in detection Parecoxib Sodium according to claim 6 and synthetic intermediate,
It is characterized in that：The Detection wavelength of the liquid chromatograph is 215nm, with 0.01mol/l KH2PO4Buffer is mobile phase
A using methanol as Mobile phase B, and carries out gradient elution, and wherein pH of buffer range is 2.5~3.5.
9. the liquid phase color in relation to substance in a kind of described in any item detection Parecoxib Sodiums of claim 1-8 and synthetic intermediate
Application of the spectral method in the detection and analysis of other substances, it is characterised in that：
Step 1：System suitability experiment：(1) reference substance for taking each impurity and something respectively is made using methanol as mixed solution
For system suitability solution；(2) liquid chromatograph is set, and the system suitability solution is injected into liquid chromatograph, record
Chromatogram, until the separating degree between each impurity peaks and something meets regulation, the fixed setting；
Step 2：Measurement experiment：(1) take something to be measured in container, solubilizer is dissolved and diluted, as test solution；
(2) take each single impurity appropriate, solubilization dilution agent, as contrast solution；(3) test solution and control are taken respectively
Solution injects liquid chromatograph, records chromatogram；(4) it according to the peak in the chromatogram of test solution, is calculated by external standard method.
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| PCT/CN2018/114746 WO2019242212A1 (en) | 2018-06-21 | 2018-11-09 | Liquid chromatography method for detecting related substances in parecoxib sodium and synthetic intermediates thereof |
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104749288A (en) * | 2015-04-16 | 2015-07-01 | 上海秀新臣邦医药科技有限公司 | Liquid chromatographic analysis method for parecoxib-sodium related substances |
| CN105372376A (en) * | 2015-11-26 | 2016-03-02 | 天津药物研究院有限公司 | Detection method of parecoxib sodium genotoxicity impurity and application thereof |
| CN105651927A (en) * | 2014-11-14 | 2016-06-08 | 泰州复旦张江药业有限公司 | An RT-HPLC detecting method for valdecoxib/parecoxib related substances |
| CN105726496A (en) * | 2014-12-12 | 2016-07-06 | 四川科伦药物研究院有限公司 | Parecoxib sodium freeze-dried powder, preparation method and powder product thereof |
| CN106692079A (en) * | 2016-12-26 | 2017-05-24 | 上药东英（江苏）药业有限公司 | Long-acting parecoxib sodium freeze-dried powder injection preparation |
| CN106908525A (en) * | 2017-01-16 | 2017-06-30 | 山东省药学科学院 | A kind of analysis method for determining SC 69124 intermediate and SC 69124 about material |
| CN108047155A (en) * | 2017-11-29 | 2018-05-18 | 浙江震元制药有限公司 | A kind of orientation Preparation method and use of the isoxazole compound of double aryl substitutions |
| 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 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104965041B (en) * | 2015-06-11 | 2016-06-29 | 成都克莱蒙医药科技有限公司 | A kind of high-efficiency liquid chromatography method for detecting of Parecoxib Sodium isomer |
-
2018
- 2018-06-21 CN CN201810666150.4A patent/CN108828127A/en active Pending
- 2018-11-09 WO PCT/CN2018/114746 patent/WO2019242212A1/en active Application Filing
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105651927A (en) * | 2014-11-14 | 2016-06-08 | 泰州复旦张江药业有限公司 | An RT-HPLC detecting method for valdecoxib/parecoxib related substances |
| CN105726496A (en) * | 2014-12-12 | 2016-07-06 | 四川科伦药物研究院有限公司 | Parecoxib sodium freeze-dried powder, preparation method and powder product thereof |
| CN104749288A (en) * | 2015-04-16 | 2015-07-01 | 上海秀新臣邦医药科技有限公司 | Liquid chromatographic analysis method for parecoxib-sodium related substances |
| CN105372376A (en) * | 2015-11-26 | 2016-03-02 | 天津药物研究院有限公司 | Detection method of parecoxib sodium genotoxicity impurity and application thereof |
| CN106692079A (en) * | 2016-12-26 | 2017-05-24 | 上药东英（江苏）药业有限公司 | Long-acting parecoxib sodium freeze-dried powder injection preparation |
| CN106908525A (en) * | 2017-01-16 | 2017-06-30 | 山东省药学科学院 | A kind of analysis method for determining SC 69124 intermediate and SC 69124 about material |
| CN108047155A (en) * | 2017-11-29 | 2018-05-18 | 浙江震元制药有限公司 | A kind of orientation Preparation method and use of the isoxazole compound of double aryl substitutions |
| 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 |
Non-Patent Citations (3)
| Title |
|---|
| XIAOLIANG JIN ET AL: "Simultaneous determination of parecoxib and its main metabolites valdecoxib and hydroxylated valdecoxib in mouse plasma with a sensitive LC–MS/MS method to elucidate the decreased drug metabolism of tumor bearing mice", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》 * |
| 李昌亮 等: "高效液相色谱法检测注射用帕瑞昔布钠中有关物质", 《中南药学》 * |
| 聂忠莉 等: "HPLC法测定帕瑞昔布钠中有关物质的方法研究", 《中国测试》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112390764A (en) * | 2019-08-19 | 2021-02-23 | 鲁南制药集团股份有限公司 | Parecoxib sodium impurity compound |
| CN110642801A (en) * | 2019-09-20 | 2020-01-03 | 深圳市祥根生物科技有限公司 | Preparation method of parecoxib meta-isomer impurity |
| 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 |
| CN111257441A (en) * | 2019-12-31 | 2020-06-09 | 河南润弘制药股份有限公司 | Method for detecting impurities in parecoxib sodium synthesis process |
| 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 |
| CN111153866A (en) * | 2020-01-19 | 2020-05-15 | 上海臣邦医药科技股份有限公司 | Parecoxib sodium disubstituted impurity and preparation method and application thereof |
| CN111153865A (en) * | 2020-01-19 | 2020-05-15 | 上海臣邦医药科技股份有限公司 | Parecoxib sodium substituted impurity and preparation method thereof |
| CN113456597A (en) * | 2020-03-30 | 2021-10-01 | 石药集团欧意药业有限公司 | Parecoxib sodium for injection and preparation method thereof |
| CN113456597B (en) * | 2020-03-30 | 2023-02-14 | 石药集团欧意药业有限公司 | Parecoxib sodium for injection and preparation method thereof |
| CN114062530A (en) * | 2021-09-30 | 2022-02-18 | 浙江美诺华药物化学有限公司 | Determination and analysis method for isomer impurities in crude chlorpheniramine maleate product |
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