CN115754084A - Analysis method of molvacoxib - Google Patents
Analysis method of molvacoxib Download PDFInfo
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- CN115754084A CN115754084A CN202211514062.5A CN202211514062A CN115754084A CN 115754084 A CN115754084 A CN 115754084A CN 202211514062 A CN202211514062 A CN 202211514062A CN 115754084 A CN115754084 A CN 115754084A
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- mobile phase
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- 238000004458 analytical method Methods 0.000 title claims abstract description 10
- 239000012535 impurity Substances 0.000 claims abstract description 25
- 239000000243 solution Substances 0.000 claims abstract description 15
- 239000011550 stock solution Substances 0.000 claims abstract description 7
- ZDPAWHACYDRYIW-UHFFFAOYSA-N 1-(4-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(F)C=C1 ZDPAWHACYDRYIW-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000005594 diketone group Chemical group 0.000 claims abstract description 6
- 238000001514 detection method Methods 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 239000013558 reference substance Substances 0.000 claims description 7
- 239000012488 sample solution Substances 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 239000000523 sample Substances 0.000 claims description 6
- 238000005070 sampling Methods 0.000 claims description 5
- AEKSRMSIOWGVRG-UHFFFAOYSA-N [4-(sulfonylamino)phenyl]hydrazine hydrochloride Chemical compound Cl.S(=O)(=O)=NC1=CC=C(C=C1)NN AEKSRMSIOWGVRG-UHFFFAOYSA-N 0.000 claims description 4
- 239000008363 phosphate buffer Substances 0.000 claims description 4
- 239000012088 reference solution Substances 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- -1 octadecyl silica Chemical compound 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 claims 1
- 229960002004 valdecoxib Drugs 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 4
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 3
- IKEURONJLPUALY-UHFFFAOYSA-N 4-hydrazinylbenzenesulfonamide;hydron;chloride Chemical compound [Cl-].NS(=O)(=O)C1=CC=C(N[NH3+])C=C1 IKEURONJLPUALY-UHFFFAOYSA-N 0.000 abstract 1
- 239000007788 liquid Substances 0.000 description 7
- 238000005303 weighing Methods 0.000 description 6
- 239000012490 blank solution Substances 0.000 description 3
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229940111134 coxibs Drugs 0.000 description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- TTZNQDOUNXBMJV-UHFFFAOYSA-N mavacoxib Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC(F)=CC=2)=CC(C(F)(F)F)=N1 TTZNQDOUNXBMJV-UHFFFAOYSA-N 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- JOVOSQBPPZZESK-UHFFFAOYSA-N phenylhydrazine hydrochloride Chemical compound Cl.NNC1=CC=CC=C1 JOVOSQBPPZZESK-UHFFFAOYSA-N 0.000 description 1
- 229940038531 phenylhydrazine hydrochloride Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
The application discloses an analysis method of molvacoxib, which comprises the following steps: preparing a content control solution; an impurity stock solution; detecting; and (6) data processing. The high performance liquid chromatography analysis method of the molvacoxib has the advantages of practicability, reliability, good stability and strong data reproducibility, and the separation degree of the molvacoxib and 3 impurities is good, namely the impurity 4-sulfonamido phenylhydrazine hydrochloride, the impurity diketone and the impurity 4-fluoroacetophenone.
Description
Technical Field
The invention relates to the technical field of analytical chemistry, in particular to an analysis method of molvacoxib.
Background
Molvacoxib, chemical name: 4- [5- (4-fluorophenyl) -3- (trifluoromethyl) pyrazol-1-yl ] benzene-1-sulfonamide belongs to non-steroidal anti-inflammatory drugs, is a novel COX-2 inhibitor, and is mainly used for diminishing inflammation and relieving pain for treating dog degenerative joint diseases. COX-2 inhibitor non-steroidal anti-inflammatory drug, mainly through inhibiting 2 type enzyme protein in Cyclooxygenase (COX) and blocking prostaglandin biosynthesis process to realize the anti-inflammatory action, the gastrointestinal side effect is much smaller than traditional anti-inflammatory drug, its analgesic anti-inflammatory activity has very large research value and broad application prospect.
In the prior art, no relevant report is provided about the molvacoxib analysis method.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to provide a high performance liquid chromatography analysis method of molvacoxib, which can simultaneously and accurately measure the content and impurities of the molvacoxib.
The technical scheme is as follows: the invention provides an analysis method of molvacoxib, which comprises the following steps:
1) Preparing a content control solution: taking a proper amount of molvacoxib reference substance, adding mobile phase for dissolving, and preparing a content reference solution with the content of about 0.2-0.5 mg/ml;
2) Impurity stock solution: placing a 4-sulfonylamino phenylhydrazine hydrochloride reagent, a diketone standard reference substance and a 4-fluoro acetophenone reagent in a same volumetric flask, dissolving the mobile phases, and shaking up to prepare an impurity stock solution with a certain limit;
3) And (3) detection: sampling the content control solution and the sample solution respectively, and recording a chromatogram;
4) Data processing: determining the peak emergence time of each component, recording the peak area, and processing data by software.
Specifically, the mobile phase is a mixed solution of a mobile phase a and a mobile phase B, and the mobile phase a is: phosphate buffer or acetate; the mobile phase B is as follows: methanol or acetonitrile.
Specifically, in the mobile phase, the volume ratio of the mobile phase A, B is (30-50): (70-50). Preferably 35.
Specifically, the column used was an octadecyl silica gel-bonded column, 250 mm. Times.4.6 mm. Times.5 μm.
Specifically, the amount of the sample was 20. Mu.l.
Specifically, the flow rate is generally controlled to be 0.6 to 1.2ml/min. Preferably 1.0ml/min.
Specifically, the column temperature is preferably 25 deg.C
Specifically, the high performance liquid chromatograph is an ultraviolet absorption detector, and the detection wavelength is 190nm-390nm, preferably 254nm.
Specifically, the sampling time is 30min.
Has the advantages that: the high performance liquid analysis method of the molvacoxib provided by the invention has the advantages of practicability, reliability, good stability and strong data reproducibility, and the separation degree of the molvacoxib and 3 impurities is good, namely the impurity 4-sulfonylamino phenylhydrazine hydrochloride, the impurity diketone and the impurity 4-fluoro acetophenone.
Drawings
FIG. 1 is a high performance liquid chromatogram of a molvacizumab blank solution.
FIG. 2 is a HPLC chromatogram of a control solution containing molvacizumab.
Figure 3 is a high performance liquid chromatogram of a control solution of molvacizumab impurity.
FIG. 4 is a high performance liquid chromatogram of a sample solution of molvacizumab.
Detailed Description
The following examples illustrate the invention in more detail, but the scope of the invention is not limited to the examples.
Example 1: detection of known impurities
Instrumentation and chromatographic conditions:
agilent 1260 high performance liquid chromatograph
And (3) chromatographic column: octadecyl silica gel bonded chromatography column (250 mm. Times.4.6 mm. Times.5 μm)
Mobile phase: phosphate buffer solution-methanol mixed solution, the volume ratio of which is 35
The flow rate was set at 1.0ml/ml, the column temperature was 25 ℃ and the detection wavelength was 254nm.
The experimental steps are as follows:
(1) Impurity stock solution: precisely weighing 60mg of 4-sulfonylamino phenylhydrazine hydrochloride reagent, placing the reagent in a 10ml volumetric flask, adding a proper amount of mobile phase, precisely weighing 47 mu l of diketone standard reference substance and 53 mu l of 4-fluoroacetophenone reagent, placing the reagent in the same volumetric flask, fixing the volume of the mobile phase, ultrasonically dissolving and shaking up; precisely measure 100. Mu.l of the solution, put it in a 10ml volumetric flask, and measure the volume of the mobile phase and shake it up.
(2) Content control solution: taking 30mg of a molvacizumab standard reference substance, precisely weighing, placing in a 10ml volumetric flask, measuring the volume of a mobile phase, ultrasonically dissolving, shaking up, precisely measuring 1ml of the solution, placing in a 10ml volumetric flask, measuring the volume of the mobile phase, and shaking up.
(3) Impurity control solution: precisely measuring 100 mul of content reference solution and 100 mul of impurity stock solution, placing in a 10ml volumetric flask, fixing the volume by mobile phase, and shaking up to obtain the sample solution.
And (3) detection: taking the sample solution, injecting 20 mu l of sample, and sampling time: and (5) recording the chromatogram after 30min.
FIG. 3 is a mixed chromatogram of molvacoxib and known impurities from example 1; as can be seen, the impurity with a retention time of 2.771 minutes is phenylhydrazine hydrochloride; 5363 the impurity in 5.391 min is 4-fluoroacetophenone; 5363 the impurity in 7.254 minutes is a diketone; the product has a retention time of 10.607 minutes and is molvacoxib, and the components can be completely separated, and the separation degree is more than 1.5. This demonstrates that good separation between molvacoxib and impurities is achieved, providing favorable preconditions for accurate determination of the content of molvacoxib.
Example 2: detection of content of molvacoxib
Instrumentation and chromatographic conditions:
agilent 1260 high performance liquid chromatograph
A chromatographic column: octadecyl silica gel bonded chromatography column (250 mm. Times.4.6 mm. Times.5 μm)
Mobile phase: phosphate buffer solution-methanol mixture, the volume ratio of which is 35
The flow rate was set at 1.0ml/ml, the column temperature was 25 ℃ and the detection wavelength was 254nm.
The experimental steps are as follows:
(1) Content control solution: taking 30mg of a molvacizumab standard reference substance, precisely weighing, placing in a 10ml volumetric flask, measuring the volume of a mobile phase, ultrasonically dissolving, shaking up, precisely measuring 1ml of the solution, placing in a 10ml volumetric flask, measuring the volume of the mobile phase, and shaking up. See figure 2 for details
(2) Sample solution: taking a sample of 30mg, precisely weighing, placing in a 10ml volumetric flask, fixing the volume of the mobile phase, ultrasonically dissolving, shaking up, precisely weighing 1ml of the solution, placing in a 10ml volumetric flask, fixing the volume of the mobile phase, and shaking up. See figure 4 for details
(3) Blank solution: a mobile phase. Detailed description of the drawings fig. 1
And (3) detection: and (3) taking the content control solution and the sample solution, injecting 20 mu l of sample respectively, and sampling time: and 30min, recording the chromatogram.
As can be seen from FIG. 1, the blank solution had no effect on the content of molvacoxib and the detection of impurities. The content of molvacoxib was 99.78% calculated by the external standard method from fig. 2 and 4.
The above description is only a preferred embodiment of the present application and is not intended to limit the present application.
Claims (9)
1. An analysis method of valdecoxib, comprising the steps of:
1) Preparing a content control solution: taking a proper amount of the molvacoxib reference substance, adding the mobile phase for dissolving, and preparing a content reference solution with the content of about 0.2-0.5 mg/ml;
2) Impurity stock solution: placing a 4-sulfonylamino phenylhydrazine hydrochloride reagent, a diketone standard reference substance and a 4-fluoro acetophenone reagent in a same volumetric flask, dissolving the mobile phases, and shaking up to prepare an impurity stock solution with a certain limit;
3) And (3) detection: respectively sampling the content control solution and the sample solution, and recording a chromatogram;
4) Data processing: determining the peak emergence time of each component, recording the peak area, and processing data by using software.
2. The method of claim 1, wherein the mobile phase is a mixture of mobile phase a and mobile phase B, and the mobile phase a is: phosphate buffer or acetate; the mobile phase B is as follows: methanol or acetonitrile.
3. The method of claim 1, wherein the mobile phase is A, B in a volume ratio of (30-50) to (70-50).
4. The method of claim 1, wherein the chromatographic column used is an octadecyl silica gel-bonded chromatographic column, 250mm x 4.6mm x 5 μm.
5. The method of claim 1, wherein the sample size is 20 μ l.
6. The method of claim 1, wherein the flow rate is generally controlled to be between 0.6 and 1.2ml/min.
7. The method of claim 1, wherein the column temperature is preferably 25 ℃.
8. The method of claim 1, wherein the hplc is an uv absorption detector with a detection wavelength of 190nm to 390nm.
9. The method of claim 1, wherein the sample time is 30min.
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| CN202211514062.5A CN115754084A (en) | 2022-11-30 | 2022-11-30 | Analysis method of molvacoxib |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020077328A1 (en) * | 2000-07-13 | 2002-06-20 | Fred Hassan | Selective cyclooxygenase-2 inhibitors and vasomodulator compounds for generalized pain and headache pain |
| US20050256130A1 (en) * | 2002-06-12 | 2005-11-17 | Chemocentryx, Inc. | Substituted piperazines |
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| US7854946B1 (en) * | 2007-05-31 | 2010-12-21 | Iowa State University Research Foundation, Inc. | Anti-inflammatory and anti-HIV compositions and methods of use |
| CN104977372A (en) * | 2015-06-21 | 2015-10-14 | 江苏正大清江制药有限公司 | Method for determining content of sulfonamide-phenylhydrazine hydrochloride in celecoxib raw medicine through high performance liquid chromatography |
| CN115246790A (en) * | 2021-04-25 | 2022-10-28 | 广东东阳光药业有限公司 | Crystal form of pyrazole compound and preparation method thereof |
-
2022
- 2022-11-30 CN CN202211514062.5A patent/CN115754084A/en active Pending
Patent Citations (6)
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|---|---|---|---|---|
| US20020077328A1 (en) * | 2000-07-13 | 2002-06-20 | Fred Hassan | Selective cyclooxygenase-2 inhibitors and vasomodulator compounds for generalized pain and headache pain |
| US20050256130A1 (en) * | 2002-06-12 | 2005-11-17 | Chemocentryx, Inc. | Substituted piperazines |
| US7854946B1 (en) * | 2007-05-31 | 2010-12-21 | Iowa State University Research Foundation, Inc. | Anti-inflammatory and anti-HIV compositions and methods of use |
| KR20090062009A (en) * | 2007-12-12 | 2009-06-17 | (주)유케이케미팜 | Process of preparing of zaltoprofen'salt, and bioequivalent test and bioavailability analysis |
| CN104977372A (en) * | 2015-06-21 | 2015-10-14 | 江苏正大清江制药有限公司 | Method for determining content of sulfonamide-phenylhydrazine hydrochloride in celecoxib raw medicine through high performance liquid chromatography |
| CN115246790A (en) * | 2021-04-25 | 2022-10-28 | 广东东阳光药业有限公司 | Crystal form of pyrazole compound and preparation method thereof |
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| Title |
|---|
| WAGMAN, AS ET AL: "Synthesis, Binding Mode, and Antihyperglycemic Activity of Potent and Selective (5-lmidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine Inhibitors of Glycogen Synthase Kinase 3", JOURNAL OF MEDICINAL CHEMISTRY, 31 December 2017 (2017-12-31) * |
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