CN105301126A - Method for analyzing topiroxostat-related substances - Google Patents
Method for analyzing topiroxostat-related substances Download PDFInfo
- Publication number
- CN105301126A CN105301126A CN201510649224.XA CN201510649224A CN105301126A CN 105301126 A CN105301126 A CN 105301126A CN 201510649224 A CN201510649224 A CN 201510649224A CN 105301126 A CN105301126 A CN 105301126A
- Authority
- CN
- China
- Prior art keywords
- impurity
- holder
- analytical approach
- department
- optimum condition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention discloses a method for analyzing topiroxostat-related substances. The method is used for determining the topiroxostat-related substances by adopting high performance liquid chromatography. The method is high in specificity, high in sensitivity, good in repeatability and high in accuracy after undergoing methodology validation and is capable of effectively controlling substances related to topiroxostat bulk pharmaceutical drugs.
Description
Technical field
The invention belongs to medical art, relate to a kind of analyzing detecting method of medicine, particularly to the method for holder department he and determination of related substances thereof.
Background technology
Holder takes charge of him, and English name is Topiroxostat, and chemical name is 4-[5-(pyridin-4-yl)-1H-1,2,4-triazole-3-base] pyridine-2-formonitrile HCN, and molecular formula is C
13h
8n
6, molecular weight is 248.24, No. CAS is 577778-58-6, and chemical structural formula is as follows:
Holder is taken charge of him and is developed by Japanese fuji medicine Co., Ltd., in June, 2013 in Japan's approval listing.It is a kind of medicine for the treatment of gout and hyperuricemia that holder takes charge of him, by suppressing xanthine oxidoreductase enzyme, suppresses the generation of uric acid.New drug or imitation medicine research and development, impurity is the Key Quality attribute affecting product.The complicated therefore Related substances separation research of the structure of impurity, physicochemical property and toxicity profile is usually one of difficult point in drug research and development.The bad reaction that medicine produces in Clinical practice, except outside the Pass having with the pharmacologically active of major component, also has much relations with the impurity existed in medicine.For ensureing the security of clinical application, need the strict impurity controlled in medicine.Through retrieval, have no Patents or the open source literature report of holder department he and Related substance method thereof at present.The analytical approach setting up a kind of holder department he and related substance thereof according to the condition such as character, destructive test of its technique, compound is significant.
Fuji of Amada Co., Ltd. medicine is applied for a patent (CN1561340B), in technique disclosed in it, reflux time is long, and impurity content is high, be unfavorable for the control of bulk drug quality, the cyano group hydrolysis that is unstable, condensation product being mainly 2-cyano group isonicotinic acid hydrazide produces caused by impurity E.Process route is the improvement route of patent CN1826335A, and under strongly acidic catalyst, the content of holder he a degradation impurity E and impurity H of department increases, and impurity E and impurity H with hold in the palm that to take charge of his structure similar, more difficult separation.
It is triazole ring that holder takes charge of him, and strong acid and highly basic is easily open loop also, causes the content of impurity B to increase.Meanwhile, a holder department he contain pyridine ring, also can further oxidized formation N-oxide impurity, be impurity F, impact holder his quality control of department to a certain extent, also need to set up effective analytical approach and carry out strict control.
In addition, preparation holder his process contaminants of department also comprises the residual and byproduct of reaction etc. of starting material, intermediate.Therefore develop the analytical approach of a kind of holder department he and related substance thereof, the method can ensure that starting material, intermediate, process contaminants and degradation impurity are effectively separated, highly sensitive, significant.
Summary of the invention
The object of the invention is to the analytical approach building a kind of holder his related substance of department, the method answers specificity good, possible degradation impurity, the initiation material that may remain and intermediate effectively can be separated with major component, and highly sensitive, can be applicable to hold in the palm his Control of Impurities of department.Main flow preparation holder his synthesis technique of department is as follows:
Process route one:
Process route two:
The present inventor takes charge of his synthesis technique (process route one, process route two) and degraded situation for above-mentioned holder, preferentially identify 8 impurity, be respectively impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G, impurity H, impurity chemical constitution and control criterion as follows:
The present invention screens chromatographic condition, 8 impurity effectively can be separated, establish Related substance method, analytical cycle is controlled at 40min, between major component and each related substance, between each related substance, all can reach baseline separation, reach the object of foregoing invention.
The present invention is achieved through the following technical solutions:
An analytical approach for holder his related substance of department, is characterized in that:
Adopting reversed-phased high performace liquid chromatographic, take octadecylsilane chemically bonded silica as chromatographic column filler, adopts UV-detector, adopt gradient elution program, A phase is disodium hydrogen phosphate buffer solution, and sodium hydrogen phosphate volumetric molar concentration is 0.002mol/L, and be 3.4 by phosphoric acid adjust ph, B phase is acetonitrile, and the de-program of gradient choosing is that 0 ~ 30min, B Phase Proportion becomes 50% from 10%, 30 ~ 31min, B Phase Proportion becomes 10% from 50%, and 31 ~ 40min, B Phase Proportion is 10%.
1. as described in analytical approach, it is characterized in that determined wavelength is 260nm ~ 280nm, optimum condition is 275nm.
2. as described in analytical approach, it is characterized in that flow velocity is 0.8 ~ 1.2ml/min, optimum condition is 1.0ml/min.
3. as described in analytical approach, it is characterized in that sample size is 10 ~ 30 μ l, optimum condition is 20 μ l.
4. as described in analytical approach, it is characterized in that in buffer solution, sodium hydrogen phosphate volumetric molar concentration is 0.002mol/L, the optimum condition of pH value is 3.4.
5. as described in analytical approach, it is characterized in that sample preparation method is: take appropriate holder and take charge of him, dissolves and dilute with methyl alcohol, being mixed with and taking charge of his concentration containing holder is the solution of 0.1 ~ 0.2mg/ml, and optimum condition is 0.2mg/ml.
The Method validation of chromatographic process
1. related substance specificity test
Preparation holder his need testing solution of department and each related substance reference substance solution, his mixed solution with each related substance of a holder department respectively, injection liquid chromatography respectively, records chromatogram.Holder department he and each magazins' layout degree result the results are shown in following table, and Fig. 1 is shown in by collection of illustrative plates:
| Impurity title | Impurity location retention time | Mixing sample introduction retention time | Degree of separation between each impurity |
| Impurity A | 5.450 | 5.526 | —— |
| Impurity B | 8.083 | 8.187 | 10.22 |
| Impurity C | 9.315 | 9.436 | 5.50 |
| Impurity D | 10.144 | 10.257 | 3.28 |
| Impurity E | 12.065 | 12.240 | 8.16 |
| Impurity F | 14.001 | 14.162 | 9.48 |
| Holder takes charge of him | 18.368 | 18.552 | 19.29 |
| Impurity G | 20.773 | 20.919 | 8.07 |
| Impurity H | 21.674 | 21.840 | 2.99 |
Result shows: a holder department, between he each related substance and major component, can reach good separation between each related substance.
2. failure test
Precision takes a holder department, and he is appropriate, and under the conditions such as highly basic, strong acid, high temperature, illumination, oxidation, carry out failure test respectively to it, sample introduction also records chromatogram, and add up the impurity situation be destroyed out, failure test impurity situation of change the results are shown in following table,
Fig. 2 ~ 7 are shown in by collection of illustrative plates:
| Impurity relative retention time | Do not destroy | Acid | Alkali | Oxidation | High temperature | Illumination |
| 0.32 | —— | 0.15 | 0.08 | —— | —— | —— |
| 0.45 (impurity B) | 0.07 | 0.09 | 0.08 | 0.05 | —— | 0.06 |
| 0.47 | —— | —— | —— | 0.11 | —— | —— |
| 0.53 | —— | —— | —— | 0.37 | —— | —— |
| 0.60 | —— | —— | —— | 0.21 | —— | —— |
| 0.66 (impurity E) | 0.05 | —— | 2.81 | 5.84 | 0.06 | 0.05 |
| 0.67 | —— | 0.06 | —— | —— | —— | 0.06 |
| 0.72 | —— | —— | 0.06 | —— | —— | —— |
| 0.73 | 0.11 | —— | 0.14 | —— | 0.10 | —— |
| 0.75 (impurity F) | 0.07 | —— | 0.06 | 2.86 | —— | 0.14 |
| 0.81 | —— | —— | 0.06 | 0.60 | —— | —— |
| 0.82 | 0.12 | —— | 0.10 | —— | 0.13 | 0.11 |
| 0.83 | 0.08 | 0.19 | 0.08 | 0.05 | 0.07 | —— |
| Holder takes charge of him | 99.18 | 99.29 | 96.40 | 89.79 | 99.29 | 99.36 |
| 1.08 | 0.09 | 0.08 | 0.08 | 0.08 | 0.09 | 0.08 |
| 1.25 | 0.06 | 0.08 | 0.06 | 0.05 | 0.07 | 0.05 |
Conclusion: he is more stable under acidity, high temperature and illumination condition in a holder department; Unstable under alkalescence and oxidizing condition, principal degradation produces impurity E in the basic conditions, and oxidizing condition principal degradation produces impurity E and impurity F; Under each degradation condition, main peak all can be separated completely with adjacent chromatographic peak; Main peak purity similarity is all greater than threshold value.
3. detectability, quantitative limit test
Signal to noise ratio (S/N ratio) method is adopted to measure detectability and the quantitative limit of a holder department he and each related substance thereof.The stock solution of preparation holder department he and each related substance thereof respectively, be diluted to finite concentration and sample introduction, calculate the ratio (signal to noise ratio (S/N ratio)) of peak height and noise, the sample detection amount that its signal to noise ratio (S/N ratio) is about 10 is quantitative limit, the sample detection amount that signal to noise ratio (S/N ratio) is about 3 is detectability, and quantitative limit and detectability test findings see the following form:
Conclusion: each impurity quantitative limit all meets mensuration requirement, and method sensitivity is higher.
4. linear test
Precision takes holder department he and each related substance, dissolve with methyl alcohol and dilute, the solution being mixed with variable concentrations sample introduction record chromatogram respectively, take concentration as horizontal ordinate, peak area is ordinate, obtain holding in the palm an equation of linear regression for department he and each related substance thereof, impurity A linear test the results are shown in following table:
Impurity B linear test the results are shown in following table:
Impurity C linear test the results are shown in following table:
Impurity D linear test the results are shown in following table:
Impurity E linear test the results are shown in following table:
Impurity F linear test the results are shown in following table:
Impurity G linear test the results are shown in following table:
Impurity H linear test the results are shown in following table
Holder his linear test of department the results are shown in following table:
Conclusion: impurity A is in 0.052 ~ 5.249 μ g/ml concentration range, impurity B is in 0.053 ~ 5.295 μ g/ml concentration range, impurity C is in 0.018 ~ 1.810 μ g/ml concentration range, impurity D is in 0.061 ~ 6.138 μ g/ml concentration range, impurity E is in 0.020 ~ 1.964 μ g/ml concentration range, impurity F is in 0.020 ~ 1.970 μ g/ml concentration range, impurity G is in 0.119 ~ 11.936 μ g/ml concentration range, impurity H is in 0.019 ~ 1.901 μ g/ml concentration range, holder takes charge of him in 0.024 ~ 2.413 μ g/ml concentration range, linear relationship is good.
5. accuracy test
Precision takes a holder department, and he is appropriate, dissolve with methyl alcohol and dilute, be mixed with the solution 9 parts being about 0.2mg/ml containing holder his concentration of department, three parts is one group, add appropriate related substance respectively to each group, make the concentration of each related substance in three groups be respectively 0.1 μ g/ml (being equivalent to need testing solution concentration 0.05%), 0.2 μ g/ml (being equivalent to need testing solution concentration 0.1%), 0.3 μ g/ml (being equivalent to need testing solution concentration 0.15%).Sample introduction also records chromatogram, and calculate the recovery, accuracy test the results are shown in following table:
| Impurity title | Average recovery rate | RSD |
| Impurity A | 89.0％ | 8.8％ |
| Impurity B | 100.2％ | 11.5％ |
| Impurity C | 106.8％ | 4.0％ |
| Impurity D | 114.3％ | 3.9％ |
| Impurity E | 86.5％ | 5.1％ |
| Impurity F | 115.0％ | 3.3％ |
| Impurity G | 95.5％ | 9.4％ |
| Impurity H | 103.7％ | 5.7％ |
Conclusion: this method accuracy is good.
Accompanying drawing explanation
Fig. 1: his related substance specificity mixed chromatogram is taken charge of in holder.
Fig. 2: holder his related substance of department does not destroy chromatogram.
Fig. 3: his related substance of a holder department is sour destroys chromatogram.
Fig. 4: his related substance alkali of a holder department destroys chromatogram.
Fig. 5: his related substance Oxidative demage chromatogram is taken charge of in holder.
Fig. 6: his related substance high temperature chromatogram is taken charge of in holder.
Fig. 7: his the related substance illumination of a holder department destroys chromatogram.
Embodiment
Following examples are used for understanding the present invention further, but are not limited to the scope of the present embodiment
The mensuration of embodiment three batches holder his a bulk drug related substance of department
Precision takes 3 batches of holders and takes charge of his each about 20mg, is placed in 100ml measuring bottle respectively, adds methyl alcohol and dissolve and be diluted to scale, shake up, as need testing solution.Precision measures need testing solution 1ml and puts in 100ml measuring bottle, with methanol dilution to scale, shakes up, then precision measures 1ml and puts in 10ml measuring bottle, with methanol dilution to scale, shakes up, in contrast solution.
Chromatographic condition: use Shimadzu 20A high performance liquid chromatograph, UV-detector, chromatographic column filler is octadecylsilane chemically bonded silica (specification is 250mm × 4.6mm, 5 μm); Be mobile phase A with buffer solution (sodium hydrogen phosphate volumetric molar concentration for 0.002mol/L, and with phosphoric acid adjust ph to 3.4), acetonitrile is Mobile phase B; Gradient elution program is 0 ~ 30min, and acetonitrile ratio becomes 50% from 10%, 30 ~ 31min, and acetonitrile ratio becomes 10% from 50%, 31 ~ 40min, and acetonitrile ratio is 10%; Determined wavelength is 275nm; Flow velocity is 1.0ml/min.
Precision measures contrast solution and each 20 μ l of need testing solution, respectively in injection liquid chromatography, sample introduction also records chromatogram, calculates the content of each related substance by the Self-control method of the correction up factor, and three batches of holder his measurement results for bulk drug related substance of department see the following form:
| Lot number | Impurity is located | 150701 | 150702 | 150703 |
| Impurity A | 5.365min | Do not detect | Do not detect | Do not detect |
| Impurity B | 7.123min | 0.023 | 0.021 | 0.023 |
| Impurity C | 7.955min | Do not detect | Do not detect | Do not detect |
| Impurity D | 9.362min | Do not detect | Do not detect | Do not detect |
| Impurity E | 10.390min | Do not detect | Do not detect | Do not detect |
| Impurity F | 12.330min | Do not detect | Do not detect | Do not detect |
| Impurity G | 19.165min | Do not detect | Do not detect | Do not detect |
| Impurity H | 19.882min | Do not detect | Do not detect | Do not detect |
| Other maximum lists are mixed | —— | 0.040 | 0.041 | 0.041 |
| Total impurities | —— | 0.087 | 0.086 | 0.087 |
Claims (6)
1. an analytical approach for holder his related substance of department, is characterized in that:
Adopting reversed-phased high performace liquid chromatographic, take octadecylsilane chemically bonded silica as chromatographic column filler, adopts UV-detector, adopt gradient elution program, A phase is disodium hydrogen phosphate buffer solution, and sodium hydrogen phosphate volumetric molar concentration is 0.002mol/L, and be 3.4 by phosphoric acid adjust ph, B phase is acetonitrile, and the de-program of gradient choosing is that 0 ~ 30min, B Phase Proportion becomes 50% from 10%, 30 ~ 31min, B Phase Proportion becomes 10% from 50%, and 31 ~ 40min, B Phase Proportion is 10%.
2. analytical approach as claimed in claim 1, it is characterized in that determined wavelength is 260nm ~ 280nm, optimum condition is 275nm.
3. the analytical approach as described in claim 1-2, it is characterized in that flow velocity is 0.8 ~ 1.2ml/min, optimum condition is 1.0ml/min.
4. the analytical approach as described in claim 1-3, it is characterized in that sample size is 10 ~ 30 μ l, optimum condition is 20 μ l.
5. the analytical approach as described in claim 1-4, it is characterized in that in buffer solution, sodium hydrogen phosphate volumetric molar concentration is 0.002mol/L, the optimum condition of pH value is 3.4.
6. the analytical approach as described in claim 1-5, is characterized in that sample preparation method is: take appropriate holder and take charge of him, dissolve and dilute with methyl alcohol, and being mixed with containing holder his concentration of department is the solution of 0.1 ~ 0.2mg/ml, and optimum condition is 0.2mg/ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510649224.XA CN105301126B (en) | 2015-10-10 | 2015-10-10 | Method for analyzing topiroxostat-related substances |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510649224.XA CN105301126B (en) | 2015-10-10 | 2015-10-10 | Method for analyzing topiroxostat-related substances |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105301126A true CN105301126A (en) | 2016-02-03 |
| CN105301126B CN105301126B (en) | 2021-02-12 |
Family
ID=55198634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510649224.XA Active CN105301126B (en) | 2015-10-10 | 2015-10-10 | Method for analyzing topiroxostat-related substances |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105301126B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106008465A (en) * | 2016-03-16 | 2016-10-12 | 江苏悦兴药业有限公司 | Topiroxostat impurity synthesis method |
| CN108017619A (en) * | 2017-12-06 | 2018-05-11 | 成都惟邦药业有限公司 | A kind of Topiroxostat impurity and preparation method thereof |
| CN112379006A (en) * | 2020-09-27 | 2021-02-19 | 江苏知原药业股份有限公司 | Method for detecting impurity C, impurity D and impurity E in topiroxostat tablets |
| CN113466378A (en) * | 2021-07-15 | 2021-10-01 | 江苏知原药业股份有限公司 | Separation and determination method for two genotoxic impurities in topiroxostat |
| CN114527213A (en) * | 2022-02-22 | 2022-05-24 | 正大制药（青岛）有限公司 | Quality detection method for topiroxostat |
| CN115308347A (en) * | 2022-09-01 | 2022-11-08 | 江苏知原药业股份有限公司 | Analysis method of nitrogen oxide impurities in topirolast |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120084787A (en) * | 2007-11-27 | 2012-07-30 | 아디아 바이오사이언스즈 인크. | Novel compounds and compositions and methods of use |
| US20150023930A1 (en) * | 2012-03-07 | 2015-01-22 | The Mclean Hospital Corporation | Aminoquinoline derivatives and uses thereof |
| CN104523691A (en) * | 2015-02-08 | 2015-04-22 | 长沙佰顺生物科技有限公司 | High-dissolution rate topiroxostat pharmaceutical composition and preparation method thereof |
| CN104814937A (en) * | 2015-04-22 | 2015-08-05 | 青岛正大海尔制药有限公司 | Topiroxostat tablet |
| CN104961730A (en) * | 2015-06-18 | 2015-10-07 | 山东金城医药化工股份有限公司 | Novel topiroxostat crystal form and method for preparing same |
-
2015
- 2015-10-10 CN CN201510649224.XA patent/CN105301126B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120084787A (en) * | 2007-11-27 | 2012-07-30 | 아디아 바이오사이언스즈 인크. | Novel compounds and compositions and methods of use |
| JP2014196373A (en) * | 2007-11-27 | 2014-10-16 | アルデア バイオサイエンシーズ インク． | New compound, composition and use method |
| US20150023930A1 (en) * | 2012-03-07 | 2015-01-22 | The Mclean Hospital Corporation | Aminoquinoline derivatives and uses thereof |
| CN104523691A (en) * | 2015-02-08 | 2015-04-22 | 长沙佰顺生物科技有限公司 | High-dissolution rate topiroxostat pharmaceutical composition and preparation method thereof |
| CN104814937A (en) * | 2015-04-22 | 2015-08-05 | 青岛正大海尔制药有限公司 | Topiroxostat tablet |
| CN104961730A (en) * | 2015-06-18 | 2015-10-07 | 山东金城医药化工股份有限公司 | Novel topiroxostat crystal form and method for preparing same |
Non-Patent Citations (2)
| Title |
|---|
| TATSUO HOSOYA等: "Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout", 《CLINICAL AND EXPERIMENTAL NEPHROLOGY》 * |
| 张利等: "抗痛风药物的临床研究进展", 《上海医药》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106008465A (en) * | 2016-03-16 | 2016-10-12 | 江苏悦兴药业有限公司 | Topiroxostat impurity synthesis method |
| CN108017619A (en) * | 2017-12-06 | 2018-05-11 | 成都惟邦药业有限公司 | A kind of Topiroxostat impurity and preparation method thereof |
| CN108017619B (en) * | 2017-12-06 | 2020-08-11 | 成都惟邦药业有限公司 | Topiroxostat impurity and preparation method thereof |
| CN112379006A (en) * | 2020-09-27 | 2021-02-19 | 江苏知原药业股份有限公司 | Method for detecting impurity C, impurity D and impurity E in topiroxostat tablets |
| CN113466378A (en) * | 2021-07-15 | 2021-10-01 | 江苏知原药业股份有限公司 | Separation and determination method for two genotoxic impurities in topiroxostat |
| CN114527213A (en) * | 2022-02-22 | 2022-05-24 | 正大制药（青岛）有限公司 | Quality detection method for topiroxostat |
| CN115308347A (en) * | 2022-09-01 | 2022-11-08 | 江苏知原药业股份有限公司 | Analysis method of nitrogen oxide impurities in topirolast |
| CN115308347B (en) * | 2022-09-01 | 2023-09-08 | 江苏知原药业股份有限公司 | Analysis method of nitrogen oxide impurities in topiroxostat |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105301126B (en) | 2021-02-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105301126A (en) | Method for analyzing topiroxostat-related substances | |
| Greenaway et al. | A high-performance liquid chromatography assay to monitor the new antiepileptic drug lacosamide in patients with epilepsy | |
| Vu et al. | Simultaneous determination of rifampicin, clarithromycin and their metabolites in dried blood spots using LC–MS/MS | |
| El-Bagary et al. | Liquid chromatographic determination of alogliptin in bulk and in its pharmaceutical preparation | |
| CN106896166B (en) | Analysis method in relation to substance in a kind of amber love song Ge Lieting raw material and its preparation | |
| CN103454370B (en) | Method for measuring phenylhydrazine compound residues in crude drugs through HPLC (high performance liquid chromatography) | |
| CN103592379A (en) | Analytic method of omeprazole related substance | |
| Hamdy et al. | Accelerated stability study of the ester prodrug remdesivir: Recently FDA‐approved Covid‐19 antiviral using reversed‐phase‐HPLC with fluorimetric and diode array detection | |
| CN103353491A (en) | Method for separating and determining alogliptin benzoate raw material and preparation thereof by liquid chromatography | |
| Khan et al. | Simultaneous determination of domperidone and Itopride in pharmaceuticals and human plasma using RP-HPLC/UV detection: Method development, validation and application of the method in in-vivo evaluation of fast dispersible tablets | |
| Kahle et al. | Simultaneous determination of voriconazole and posaconazole concentrations in human plasma by high-performance liquid chromatography | |
| CN105388223A (en) | Detection method for decitabine impurities | |
| CN109900830A (en) | Using the method and application of sulfonamides impurity in HPLC separation determination celecoxib | |
| Bahgat et al. | HPLC-DAD technique for the quantification of a recently approved anti-diabetic triple combination along with two toxic official impurities: Toxicity confirmation aided by molecular docking application | |
| Kumar et al. | Development and validation of RP-HPLC method for simultaneous estimation of nimesulide, phenylephrine hydrochloride, chlorpheniramine maleate and caffeine anhydrous in pharmaceutical dosage form | |
| CN109307716B (en) | Detection method of brexpiprazole related substance | |
| CN103364500B (en) | A method of with liquid chromatography for separating and determining bilastine raw material and its preparation | |
| CN114965720A (en) | Method for determining related substances of vortioxetine hydrobromide | |
| CN104764840B (en) | The separation of palonosetron Hcl and impurity and detection method | |
| Mallayasamy et al. | A sensitive and selective HPLC method for estimation of lamotrigine in human plasma and saliva: application to plasma-saliva correlation in epileptic patients | |
| CN115308347B (en) | Analysis method of nitrogen oxide impurities in topiroxostat | |
| Qin et al. | Development and validation of a cost‐effective and sensitive bioanalytical HPLC‐UV method for determination of lopinavir in rat and human plasma | |
| CN104458932B (en) | A kind of Cetirizine Hydrochloride granule related substance detection method | |
| Hasan et al. | Dual wavelength RP-HPLC method for simultaneous determination of two antispasmodic drugs: an application in pharmaceutical and human serum | |
| Tamboli et al. | RP-HPLC method for simultaneous estimation of cefepime hydrochloride and tazobactam sodium in bulk and pharmaceuticals |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |