CN108088923A - A kind of Telmisartan impurity method for separating and detecting - Google Patents
A kind of Telmisartan impurity method for separating and detecting Download PDFInfo
- Publication number
- CN108088923A CN108088923A CN201711326660.9A CN201711326660A CN108088923A CN 108088923 A CN108088923 A CN 108088923A CN 201711326660 A CN201711326660 A CN 201711326660A CN 108088923 A CN108088923 A CN 108088923A
- Authority
- CN
- China
- Prior art keywords
- solution
- impurity
- telmisartan
- methanol
- reference substance
- 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.)
- Pending
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of Telmisartan impurity method for separating and detecting, method of the invention, step is as follows：Step 1, telmisartan active pharmaceutical ingredient or its preparation are taken, is dissolved into methanol solvate and obtains test solution；Step 2, test solution is injected into high performance liquid chromatograph, obtains chromatogram；Step 3, according to the calculated by peak area Telmisartan of chromatogram and its content of impurity；High-efficient liquid phase chromatogram condition is as follows：Chromatographic column：ODS 2C18, flow velocity：1.0ml/min, column temperature：40 DEG C, wavelength：230nm, sample size：10μl.Gradient elution table is as follows：。
Description
Technical field
The present invention relates to the detection method of impurity in medical compounds, more particularly to a kind of Telmisartan impurity separation detection
Method
Background technology
Telmisartan category angiotensin II receptor antagonist, optionally, the difficult retardance AT1 reversed by
Body, and on other receptor systems without influence, more particularly, to the receptor of cardiovascular system, clinic is mainly used for treating primary height
Blood pressure.
Telmisartan is that bioavilability is higher in similar drugs, especially longest one of half-life period, takes one daily
It is secondary, one every time, can the interior steady decompression when 24 is small, have a clear superiority in curative effect, use and adverse reaction etc..
Telmisartan in the synthesis process can residual fraction impurity, such as impurity E and impurity F
Their structure is as follows：
Impurity E:
Molecular weight：428.17
Impurity F:
Molecular weight：513.63
Since structure is similar, the two separation is difficult, the related substance method of Telmisartan described in prior art, impurity E
It is only 0.248 with F separating degrees, is unable to reach and is kept completely separate (see Fig. 1).
The content of the invention：
The present invention provides the separation method of a kind of impurity E and impurity F, while provides the inspection of a kind of Telmisartan and its impurity
Survey method.The detection method of the present invention, comprises the following steps：
Step 1, telmisartan active pharmaceutical ingredient or its preparation are taken, is dissolved into solvent and obtains test solution；
Step 2, test solution is injected into high performance liquid chromatograph, obtains chromatogram；
Step 3, according to the calculated by peak area Telmisartan of chromatogram and its content of impurity；
Wherein：Solvent described in step 1 is methanol.
Wherein, test sample preparation method is as follows described in step 1：
Telmisartan raw material or appropriate powder formulation are taken, methanol is added quantitatively to be configured to the molten of every 1ml 0.5mg containing Telmisartan
Liquid.
Wherein, methanol is added to be configured in the solution processes of every 1ml 0.5mg containing Telmisartan, optional can add in hydrogen-oxygen
Change sodium solution hydrotropy.
The concentration of sodium hydroxide solution is the sodium hydroxide solution of 1mol/L, and addition is 100 μ l.Wherein, efficient liquid
Phase chromatographic condition is as follows：, chromatographic column：ODS-2C18, flow velocity：1.0ml/min, column temperature：40 DEG C, wavelength：230nm, sample size：10
μ l, mobile phase are formulated as follows：
Mobile phase A：In the purified water for weighing potassium dihydrogen phosphate 2.0g and a water sodium pentanesulfonate 3.8g to 1000ml, use
Phosphoric acid,diluted adjusts pH value to 3.0；
Mobile phase B：Methanol：Acetonitrile=1:4(V/V)
Gradient elution table 1
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 60 | 40 |
| 3 | 60 | 40 |
| 48 | 20 | 80 |
| 55 | 20 | 80 |
| 60 | 60 | 40 |
| 70 | 60 | 40。 |
The detection method of the present invention when needing using own control product, prepares own control product solution, preparation method is such as
Under：5 μ g/ml further are made with methanol dilution, as 1% own control in the Telmisartan test solution that step 1 is prepared
Product solution.
The detection method of the present invention when needing using impurity reference substance, prepares impurity reference substance solution, preparation method is such as
Under：It takes each impurity reference substance (A, B, C, E, F, G, H, I, intermediate ester) in right amount, is dissolved with methanol and quantify dilution every 1ml is made
Solution containing 1mg, as each impurity reference substance stock solution；
The detection method of the present invention, when needing using system suitability solution, compounding system adaptability solution, preparation side
Method is as follows：Measure each impurity reference substance (A, B, C, E, F, G, H, I, intermediate ester) storing solution 1ml Telmisartans raw material or preparation
Appropriate powder adds methanol quantitatively to dilute and mixed solutions of every 1ml containing each 2 μ g of impurity, Telmisartan 0.5mg is made, as system
Adaptability solution.
Preferably, detection method of the invention, comprises the following steps：
Step 1, solution is prepared：
Telmisartan raw material or appropriate powder formulation are taken, adds the 100 μ l hydrotropies of sodium hydroxide of 1mol/L, is determined with methanol dilution
Hold to 0.5mg/ml, make test solution；
It dilutes again as needed and 5 μ g/ml solution is made, as own control product solution；
Step 2, measure
By test solution and 1% own control solution, high performance liquid chromatograph is injected separately into, obtains chromatogram, according to
Chromatogram calculates the content of each impurity of Telmisartan in sample.
As needed, following operate can also be carried out：
Step 3, system suitability solution is prepared：
It takes each impurity reference substance (A, B, C, E, F, G, H, I, intermediate ester) each appropriate, dissolved with methanol and quantifies dilution system
Into solution of every 1ml containing 1mg, as each impurity reference substance stock solution；Measure each impurity reference substance (A, B, C, E, F, G, H, I,
Intermediate ester) storing solution 1ml and Telmisartan raw material or appropriate powder formulation, methanol is added quantitatively to dilute, every 1ml is made containing each
Impurity is 2 μ g, the mixed solution of Telmisartan 0.5mg, as system suitability solution.
Step 4, measure
By system suitability solution and 1% own control solution, high performance liquid chromatograph is injected separately into, obtains chromatogram,
Situations such as detecting the content and separating degree of each impurity of Telmisartan.
The method of the present invention, can be kept completely separate impurity E and F in Telmisartan, separating degree reaches 1.992>1.5 baseline
Separation requirement (see Fig. 5) is so as to according to respective characteristic peak, calculating its content, to control the quality of product.
The detection method of the present invention is obtained by screening, and screening process is as follows：
1：First the detection of 3 producer's raw materials is carried out according to the related substance method of preparation of pharmacopoeia of each country：
1. with reference to European Pharmacopoeia
Chromatographic column：Welch, C18, 4.6 × 150mm, 5um
Wavelength：230nm
Column temperature：40℃
Flow velocity：1.0mL/min
Sample size：10μl
Mobile phase：
Mobile phase A：PH3.0 phosphate (contains ion-pairing agent)
Mobile phase B:Methanol：Acetonitrile (1：4)(V/V)
Gradient elution table 2
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 70 | 30 |
| 3 | 70 | 30 |
| 28 | 20 | 80 |
Diluent：100 μ l 1mol/L sodium hydroxides+methanol solution
2. with reference to United States Pharmacopeia
Chromatographic column：Welch, C18, 4.6 × 150mm, 5um
Wavelength：230nm
Column temperature：40℃
Flow velocity：1.0mL/min
Sample size：10μl
Mobile phase：
Mobile phase A：PH3.0 phosphate (contains ion-pairing agent)
Mobile phase B:Methanol：Acetonitrile (1：4)(V/V)
Gradient elution table 3
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 70 | 30 |
| 2 | 70 | 30 |
| 27 | 20 | 80 |
| 32 | 20 | 80 |
| 32.1 | 70 | 30 |
| 37 | 70 | 30 |
Diluent：100 μ l 1mol/L sodium hydroxides+methanol solution
3. with reference to Japanese Pharmacopoeia
Chromatographic column：Welch, C18, 4.6 × 150mm, 5um
Wavelength：230nm
Column temperature：40℃
Flow velocity：1.0mL/min
Sample size：10μl
Mobile phase：
Mobile phase A：PH3.0 phosphate (contains ion-pairing agent)
Mobile phase B:Methanol：Acetonitrile (1：4)(V/V)
Gradient elution table 4
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 70 | 30 |
| 25 | 20 | 80 |
Diluent：100 μ l 1mol/L sodium hydroxides+methanol solution
4. with reference to Chinese Pharmacopoeia version in 2015
Chromatographic column：Welch, C18, 4.6 × 150mm, 5um
Wavelength：230nm
Flow velocity：1.0mL/min
Sample size：20μl
Mobile phase：
Mobile phase A：0.1% potassium dihydrogen phosphate-methanol (35：65, containing 0.2% triethylamine, with phosphorus acid for adjusting pH extremely
5.0)
Mobile phase B:Methanol
Gradient elution table 5
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 100 | 0 |
| 10 | 100 | 0 |
| 20 | 45 | 45 |
| 25 | 45 | 45 |
| 25.1 | 100 | 0 |
| 35 | 100 | 0 |
Diluent：100 μ l 1mol/L sodium hydroxides+methanol solution
The preparation of test solution：
It takes this product (producer A, producer B, producer C) in right amount, diluent is added quantitatively to dilute, every 1ml is made containing about Telmisartan
The solution of 0.5mg.
Precision measures above-mentioned solution and blank solvent, is injected separately into liquid chromatograph, records chromatogram.The result shows that it is shown in Table
6
Table 6
In conclusion the European Pharmacopoeia investigated, United States Pharmacopeia, 4 kinds of detection methods of Japanese Pharmacopoeia and Chinese Pharmacopoeia, wherein in
State's pharmacopeia detection impurity number is minimum, and European Pharmacopoeia detection impurity number is most, wherein being employed there are three National Pharmacopeia
PH3.0 phosphate (contains ion-pairing agent), and organic phase and all acetonitrile and methanol, simply gradient is different, and European Pharmacopoeia is given
Go out detailed impurity information, therefore fixed tentatively the related substance method of European Pharmacopoeia, carry out impurity quantification and optimization on this basis.
The selection of wavelength：
According to the full wavelength scanner of high performance liquid chromatography PDA, it is known that the optimal absorption wavelength of each impurity the results are shown in Table 7：
Table 7
| Sample | Optimal absorption wavelength is 1. | Optimal absorption wavelength is 2. | Optimal absorption wavelength is 3. |
| Impurity A | 202nm | 231nm | 295nm |
| Impurity B | 194nm | - | - |
| Impurity C | 194nm | - | - |
| Impurity E | 194nm | - | - |
| Impurity F | 194nm | - | - |
| Impurity G | 195nm | 221nm | 297nm |
| Impurity H | 196nm | 251nm | - |
| Impurity I | 196nm | 255nm | - |
| Intermediate ester | 196nm | 230nm | 298nm |
| Telmisartan | 208nm | 227nm | 298nm |
The results show：According to the ultraviolet full wavelength scanner figure of each sample, 10 samples are in 194nm vicinity
There is absorption, it is also the optimal absorption wavelength of solvent methanol to consider this wavelength, has end to absorb interference, therefore is not selected, wherein there are 6
Sample also has larger absorbing wavelength in 230nm, is 230nm with reference to the Detection wavelength that each pharmacopeia method is selected, considers,
Therefore wavelength 230nm of the selection detection this product in relation to substance.
Each impurity positioning and the optimization of method：
It takes each impurity reference substance (A, B, C, E, F, G, H, I, intermediate ester) each appropriate, is dissolved with diluent and quantify dilution
Solution of every 1ml containing about 2 μ g is made, as each impurity reference substance solution.
Take this product appropriate, solubilizer, which quantitatively dilutes, is made solution of every 1ml containing about Telmisartan 0.5mg, as test sample
Solution.
Precision measures each impurity reference substance (A, B, C, E, F, G, H, I, intermediate ester) storing solution 1ml and this product is each appropriate,
Solubilizer, which quantitatively dilutes, is made every 1ml containing about the mixed solution that each impurity is 2 μ g, Telmisartan 0.5mg, as system suitability
Solution.
Precision measures above-mentioned solution and each 10 μ l of solvent, liquid chromatograph is injected separately into, according to related under European Pharmacopoeia
Gradient elution, record chromatogram (see Fig. 1).
The results show：The non-appearances of impurity C and H, impurity E and F are not kept completely separate, and separating degree only has 0.248, to optimize item
Part.
1. changing condition of gradient elution is：
Gradient elution table 8
As a result understand：Impurity E and F are not still kept completely separate, and separating degree only has 1.062, see (Fig. 2) and blank solvent is done
Disturbing matter G, C, H, will continue optimal conditions.
2. replace long chromatographic column：Wonda Crat ODS-2,4.6 × 250mm, 5um, Japanese Shimadzu, the result is shown in (Fig. 3)
As a result understand：Impurity E and F have been kept completely separate, but blank solvent still has interference to impurity G and main peak.
3. changing condition of gradient elution is：
Gradient elution table 9
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 60 | 40 |
| 3 | 60 | 40 |
| 48 | 20 | 80 |
| 55 | 20 | 80 |
| 60 | 60 | 40 |
| 70 | 60 | 40 |
The result is shown in (Fig. 4)
The result shows that：Each impurity peaks are completely separable, but blank solvent has main peak a little interference, continue to optimize item
Part.Consider that main peak easily remains, before preparing sample introduction, to walk a few pin blank solvents more and see down, see (Fig. 5).
The result shows that：Under the chromatographic condition, solvent is noiseless to this product impurity, and each impurity can separate, therefore fixes tentatively this
Method is related substance method.
Compared to the prior art, advantage is as follows by the present invention：
1：Impurity E and F can be kept completely separate, and reach separation requirement.
2：It can detect 9 known impurities peaks and main peak, can reach baseline separation (separating degree>1.5).
Description of the drawings：
Fig. 1, Telmisartan chromatogram
Fig. 2, Telmisartan chromatogram
Fig. 3, Telmisartan chromatogram
Fig. 4, Telmisartan chromatogram
Fig. 5, Telmisartan chromatogram
Specific embodiment：
It further illustrates the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1
Step 1, solution is prepared：
Telmisartan raw material or appropriate powder formulation are taken, adds the 100 μ l hydrotropies of sodium hydroxide of 1mol/L, is determined with methanol dilution
Hold to 0.5mg/ml, make test solution；
It dilutes again as needed and 5 μ g/ml solution is made, as own control product solution；
Step 2, system suitability solution is prepared：
It takes each impurity reference substance (A, B, C, E, F, G, H, I, intermediate ester) each appropriate, dissolved with methanol and quantifies dilution system
Into solution of every 1ml containing 1mg, as each impurity reference substance stock solution；Measure each impurity reference substance (A, B, C, E, F, G, H, I,
Intermediate ester) storing solution 1ml and Telmisartan raw material or appropriate powder formulation, methanol is added quantitatively to dilute, every 1ml is made containing each
Impurity is 2 μ g, the mixed solution of Telmisartan 0.5mg, as system suitability solution；
Step 3, measure
By system suitability solution and 1% own control solution, high performance liquid chromatograph is injected separately into, obtains chromatogram,
According to chromatogram, the content of each impurity of Telmisartan in sample is calculated.Wherein, the chromatographic condition of the high performance liquid chromatograph is such as
Under：
Preparation of the Telmisartan in relation to mobile phase：
Mobile phase A：In the purified water for weighing potassium dihydrogen phosphate 2.0g and a water sodium pentanesulfonate 3.8g to 1000ml, use
Phosphoric acid,diluted adjusts pH value to 3.0.
Mobile phase B：Methanol：Acetonitrile=1:4 (V/V), mixing.
According to high performance liquid chromatography,
Chromatographic column：Wonda Crat ODS-2,4.6 × 250mm, 5um, Japanese Shimadzu；
Detection wavelength is 230nm,
Flow velocity：1.0mL/min
Column temperature：40℃
Sample size：10ul
Gradient elution table 10
| Time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 60 | 40 |
| 3 | 60 | 40 |
| 48 | 20 | 80 |
| 55 | 20 | 80 |
| 60 | 60 | 40 |
| 70 | 60 | 40 |
Precision measures test solution l0 μ L, injecting chromatograph.
Claims (10)
1. a kind of Telmisartan impurity method for separating and detecting, which is characterized in that comprise the following steps：
Step 1, telmisartan active pharmaceutical ingredient or its preparation are taken, is dissolved into solvent and obtains test solution；
Step 2, test solution is injected into high performance liquid chromatograph, obtains chromatogram；
Step 3, according to the calculated by peak area Telmisartan of chromatogram and its content of impurity.
2. detection method according to claim 1, which is characterized in that wherein：Solvent described in step 1 is methanol.
3. detection method according to claim 1, which is characterized in that wherein, test sample preparation method described in step 1 is such as
Under：
Telmisartan raw material or appropriate powder formulation are taken, methanol is added quantitatively to be configured to the solution of every 1ml 0.5mg containing Telmisartan.
4. detection method according to claim 3, which is characterized in that wherein, methanol is added to be configured to every 1ml containing Telmisartan
In the solution processes of 0.5mg, optional can add in sodium hydroxide solution hydrotropy.
5. detection method according to claim 4, which is characterized in that the concentration of sodium hydroxide solution is the hydrogen of 1mol/L
Sodium hydroxide solution, addition are 100 μ l.
6. detection method according to claim 1, which is characterized in that wherein
High-efficient liquid phase chromatogram condition is as follows：
Chromatographic column：ODS-2C18, flow velocity：1.0ml/min, column temperature：40 DEG C, wavelength：230nm,
Sample size：10 μ l, mobile phase are formulated as follows：
Mobile phase A：In the purified water for weighing potassium dihydrogen phosphate 2.0g and a water sodium pentanesulfonate 3.8g to 1000ml, phosphoric acid,diluted is used
PH value is adjusted to 3.0；
Mobile phase B：Methanol：Acetonitrile=1:4(V/V)
Gradient elution table is as follows：
7. detection method according to claim 1, which is characterized in that when needing using own control product, prepare itself
Reference substance solution, preparation method are as follows：The Telmisartan test solution that step 1 is prepared, is further made 5 with methanol dilution
μ g/ml, as 1% own control product solution.
8. detection method according to claim 1, which is characterized in that when needing using impurity reference substance, prepare impurity
Reference substance solution, preparation method are as follows：Take each impurity reference substance (A, B, C, E, F, G, H, I, intermediate ester) in right amount, it is molten with methanol
It solves and quantifies dilution and solution of every 1ml containing 1mg is made, as each impurity reference substance stock solution.
9. detection method according to claim 1, which is characterized in that when needing using system suitability solution, prepare
System suitability solution, preparation method are as follows：Measure each impurity reference substance (A, B, C, E, F, G, H, I, intermediate ester) storing solution
1ml and Telmisartan raw material or appropriate powder formulation add methanol quantitatively to dilute and every 1ml are made containing each 2 μ g of impurity, Telmisartan
The mixed solution of 0.5mg, as system suitability solution.
10. detection method according to claim 1, which is characterized in that comprise the following steps：
Step 1, solution is prepared：
Telmisartan raw material or appropriate powder formulation are taken, adds the 100 μ l hydrotropies of sodium hydroxide of 1mol/L, is settled to methanol dilution
0.5mg/ml makees test solution；
It dilutes again as needed and 5 μ g/ml solution is made, as own control product solution；
Step 2, measure
By test solution and 1% own control solution, high performance liquid chromatograph is injected separately into, obtains chromatogram, according to chromatography
Figure calculates the content of each impurity of Telmisartan in sample.
If desired, carry out following operation：
Step 3, system suitability solution is prepared：
It takes each impurity reference substance (A, B, C, E, F, G, H, I, intermediate ester) each appropriate, is dissolved with methanol and quantify dilution and be made often
Solution of the 1ml containing 1mg, as each impurity reference substance stock solution；Measure each impurity reference substance (A, B, C, E, F, G, H, I, centre
Body ester) storing solution 1ml and step 1 test solution it is appropriate, methanol is added quantitatively to dilute and every 1ml is made containing each impurity is 2 μ g, replaces
The mixed solution of meter Sha Tan 0.5mg, as system suitability solution；
Step 4, measure
By system suitability solution and 1% own control solution injection high performance liquid chromatograph, chromatogram is obtained, detection is for meter Sha
Situations such as content and separating degree of smooth each impurity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711326660.9A CN108088923A (en) | 2017-12-13 | 2017-12-13 | A kind of Telmisartan impurity method for separating and detecting |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711326660.9A CN108088923A (en) | 2017-12-13 | 2017-12-13 | A kind of Telmisartan impurity method for separating and detecting |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108088923A true CN108088923A (en) | 2018-05-29 |
Family
ID=62175454
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711326660.9A Pending CN108088923A (en) | 2017-12-13 | 2017-12-13 | A kind of Telmisartan impurity method for separating and detecting |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108088923A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109928932A (en) * | 2019-05-06 | 2019-06-25 | 浙江华海药业股份有限公司 | A kind of Telmisartan methylene dimer and preparation method thereof |
| CN110836943A (en) * | 2019-11-29 | 2020-02-25 | 江西杏林白马药业有限公司 | Analysis method for impurity detection of telmisartan tablets and telmisartan capsules |
| CN113514577A (en) * | 2021-05-11 | 2021-10-19 | 南京双科医药开发有限公司 | Method for detecting related substances of telmisartan and telmisartan tablets |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102253129A (en) * | 2010-05-21 | 2011-11-23 | 上海市公共卫生临床中心 | Method for simultaneously testing plasma concentration of multiple anti-human-immunodeficiency-virus (HIV) medicaments |
-
2017
- 2017-12-13 CN CN201711326660.9A patent/CN108088923A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102253129A (en) * | 2010-05-21 | 2011-11-23 | 上海市公共卫生临床中心 | Method for simultaneously testing plasma concentration of multiple anti-human-immunodeficiency-virus (HIV) medicaments |
Non-Patent Citations (3)
| Title |
|---|
| M. RAMA MOHANA REDDY等: "STABILITY-INDICATING HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF LOW LEVEL IMPURITIES OF TELMISARTAN AND HYDROCHLOROTHIAZIDE IN TABLET DOSAGE FORMS", 《INTERNATIONAL JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES》 * |
| 吴赟等: "RP-HPLC梯度洗脱法测定替米沙坦中有关物质", 《现代药物与临床》 * |
| 欧洲药品质量管理局: "《EUROPEAN PHARMACOPOEIA 7.0》", 15 July 2010 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109928932A (en) * | 2019-05-06 | 2019-06-25 | 浙江华海药业股份有限公司 | A kind of Telmisartan methylene dimer and preparation method thereof |
| CN110836943A (en) * | 2019-11-29 | 2020-02-25 | 江西杏林白马药业有限公司 | Analysis method for impurity detection of telmisartan tablets and telmisartan capsules |
| CN113514577A (en) * | 2021-05-11 | 2021-10-19 | 南京双科医药开发有限公司 | Method for detecting related substances of telmisartan and telmisartan tablets |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Krynitsky et al. | Determination of perchlorate anion in foods by ion chromatography− tandem mass spectrometry | |
| CN108088923A (en) | A kind of Telmisartan impurity method for separating and detecting | |
| Lu et al. | Simultaneous determination of five diamide insecticides in food matrices using carbon nanotube multiplug filtration cleanup and ultrahigh-performance liquid chromatography–tandem mass spectrometry | |
| US11946917B2 (en) | Detection method of polyethylene glycol monomethyl ether residue in medicinal materials | |
| CN109374784B (en) | Method for separating and measuring related substances of dapagliflozin bulk drug by using HPLC (high performance liquid chromatography) | |
| Lopes et al. | Quantification of carbamazepine and its active metabolite by direct injection of human milk serum using liquid chromatography tandem ion trap mass spectrometry | |
| CN105467021B (en) | A kind of method in relation to substance in HPLC method separation determination paricalcitol bulk pharmaceutical chemicals and preparation | |
| Katakam et al. | Development and validation of LC–MS method for the determination of heptaethylene glycol monomethyl ether in benzonatate bulk drugs | |
| CN109406695A (en) | It is a kind of at the same separate analysis paricalcitol injection in the high performance liquid chromatography of paricalcitol and isomer impurities | |
| CN111141850A (en) | Liquid phase detection and separation method for acetaminophen bulk drug related substances | |
| Nannetti et al. | A sensitive and validated HPLC‐UV method for the quantitative determination of the new antifungal drug isavuconazole in human plasma | |
| CN105806966A (en) | Quality control method for high optical purity folic acid preparation process | |
| CN107402259B (en) | Method for detecting chiral isomer in carfilzomib | |
| CN113759048B (en) | Inspection method of mono-tert-butyl octadecanedioate | |
| CN107941946B (en) | Detection method of Vonoprazan fumarate | |
| Mohammed et al. | Development and validation of a chiral liquid chromatographic assay for enantiomeric separation and quantification of verapamil in rat plasma: Stereoselective pharmacokinetic application | |
| Wang et al. | Detection of two genotoxic impurities in drug substance and preparation of imatinib mesylate by LC–MS/MS | |
| Gu et al. | Development and validation of a stability-indicating HPLC method for determination of voriconazole and its related substances | |
| CN111413425B (en) | Ultra-high performance liquid chromatography analysis method for clozapine-related substances | |
| CN108872405A (en) | A kind of HPLC analyzing detecting method of the lodoxamide tromethamine in relation to substance | |
| CN111141849A (en) | Liquid phase detection and separation method for positional isomer of dexmedetomidine starting material | |
| Turković et al. | Optimisation of Solid-Phase Extraction and LC-MS/MS Analysis of Six Breast Cancer Drugs in Patient Plasma Samples | |
| CN111610273B (en) | High performance liquid chromatography analysis method for dihydralazine sulfate related substances | |
| CN107976501B (en) | Detection method of 1- (3-ethoxy-4-methoxyphenyl) -2- (methylsulfonyl) ethylamine | |
| CN107966509B (en) | Detection method of (S) -1- (3-ethoxy-4-methoxyphenyl) -2- (methylsulfonyl) ethylamine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180529 |