CN101929985A - Method for measuring atorvastatin calcium associated matters by high performance liquid chromatography - Google Patents
Method for measuring atorvastatin calcium associated matters by high performance liquid chromatography Download PDFInfo
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- CN101929985A CN101929985A CN2009100877972A CN200910087797A CN101929985A CN 101929985 A CN101929985 A CN 101929985A CN 2009100877972 A CN2009100877972 A CN 2009100877972A CN 200910087797 A CN200910087797 A CN 200910087797A CN 101929985 A CN101929985 A CN 101929985A
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- atorvastatin calcium
- acetonitrile
- tetrahydrofuran
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- citrate
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Abstract
The invention discloses a method for measuring atorvastatin calcium associated matters by high performance liquid chromatography. In the method, a chromatographic column using cyano silane bonded silica gel as a filler is adopted, acetonitrile serves as an organic phase, a mixed solvent, of which the water phase is buffer salt, serves as a flowing phase, and the method can be used for control the quality of atorvastatin calcium and medicinal compositions which contain the atorvastatin calcium.
Description
Technical field:
The present invention relates to a kind of high-efficient liquid phase chromatogram process measuring method of high performance liquid chromatogram method, particularly a kind of atorvastatin calcium associated matters.
Background technology:
Atorvastatin calcium is the enanthate trihydrate, the various diseases that the treatment high fat of blood causes.Molecular formula is C
66H
68CaF
2N
4O
103H
2O, chemical being called [R-(R, R)]-2-(4-fluorophenyl)-β, β dihydroxy-5-(1-Methylethyl)-3-phenyl-4-[(aniline) hydroxyl]-1-hydrogen-pyrroles-1-enanthic acid calcium trihydrate, its chemical structural formula is as follows:
The main intermediate impurity of Atorvastatin calcium has 2, and wherein, intermediate-1 generates in the building-up process of Atorvastatin calcium, and another is a starting material-0, is the starting material of intermediate-1.These main intermediate are very important for the quality control of the quality production run of final products.
This law adopts the cyano group chromatographic column to realize the mensuration of atorvastatin calcium associated matters fast and accurately, thereby has realized the control of Atorvastatin calcium intermediate impurity, has guaranteed the quality controllable of Atorvastatin calcium, has realistic meaning.
Summary of the invention:
The object of the present invention is to provide a kind of method, can be used for the preparation process of Atorvastatin calcium and the quality control of final products with the high efficiency liquid chromatography for separating and determining atorvastatin calcium associated matters.
The invention provides a kind of method with the high-performance liquid chromatogram determination atorvastatin calcium associated matters, selecting cyano group silane key and silica gel for use is the chromatographic column of filler, is organic phase with acetonitrile and tetrahydrofuran, and water is that buffer salt is as moving phase.
The moving phase organic phase of the inventive method is selected from acetonitrile, methyl alcohol, tetrahydrofuran, preferred acetonitrile and tetrahydrofuran.
In the method moving phase of the present invention, organic phase is acetonitrile and tetrahydrofuran, and the ratio of acetonitrile, tetrahydrofuran and water is: 30～40: 10～20: 50～70, and preferred 30: 12: 58.
Method water of the present invention is a wherein a kind of or potpourri of sodium citrate, ammonium citrate.Citrate preferably citric acid ammonium.
The invention provides a kind of method, can realize by the following method with the high-performance liquid chromatogram determination atorvastatin calcium associated matters:
1) gets the Atorvastatin calcium sample and use acetonitrile-0.05mol/L ammonium citrate solution (with ammoniacal liquor adjust pH to 7.4) (50: 50) dissolving in right amount, and be mixed with the sample solution that every 1ml contains Atorvastatin calcium 1mg.
2) flow rate of mobile phase being set is 0.5～1.5ml/min, and the flow velocity of moving phase is preferably 1ml/min; Detect wavelength 210～280nm, the optimum detection wavelength is 246nm; Select the cyano group chromatographic column for use; 20～30 ℃ of chromatographic column column temperatures, column temperature the best are 25 ℃.
3) get 1) sample solution 5～50ul, preferred 10ul injects high performance liquid chromatograph, finishes the mensuration of atorvastatin calcium associated matters.
Wherein:
High performance liquid chromatograph: Tianjin, island: LC-10ATvp, SPD-10Avp
Chromatographic column: cyano group silane group chromatographic column (250mm * 4.6mm, 5 μ m)
Moving phase: 0.05mol/L ammonium citrate solution (regulating the pH value with ammoniacal liquor is 4.0 ± 0.05)-tetrahydrofuran-acetonitrile (58: 12: 30)
Thinning agent: acetonitrile-0.05mol/L ammonium citrate solution (with ammoniacal liquor adjust pH to 7.4) (50: 50)
Flow velocity: 1.0mL/min
Detect wavelength: 246nm
Column temperature: 25 ℃
Sampling volume: 10 μ L
The present invention adopts effectively compartment analysis atorvastatin calcium associated matters of cyano group chromatographic column, with acetonitrile-0.05mol/L ammonium citrate solution (with ammoniacal liquor adjust pH to 7.4) (50: 50) dissolving, can avoid sample and moving phase to generate flocculent deposit, thereby guarantee the accuracy that impurity detects.The present invention can effectively measure the related substance of Atorvastatin calcium, the method simple and fast, and the sensitivity for analysis height, the result can be used for Atorvastatin calcium and contains the quality control of the pharmaceutical composition of Atorvastatin calcium accurately and reliably.
Description of drawings
The liquid chromatogram of Fig. 1 Atorvastatin calcium and intermediate impurity thereof
The high-efficient liquid phase chromatogram of Fig. 2 Atorvastatin calcium
Fig. 3 atorvastatin calcium associated matters high-efficient liquid phase chromatogram
Fig. 4 Atorvastatin calcium and intermediate impurity system durability high-efficient liquid phase chromatogram thereof
Embodiment:
Following examples are used for further understanding the present invention, but are not limited to the scope of this enforcement.
Embodiment 1
Instrument and condition
Day island proper Tianjin LC-10ATVP pump, Tianjin, island SPD-10AVP ultraviolet-visible multiwavelength detector, RHEODYNE 7725i injector and TL9900 chromatographic data workstation, chromatographic column: cyano group post 250 * 4.6mm, 5 μ m, ultraviolet detection wavelength: 246nm, moving phase: 0.05mol/L ammonium citrate solution (regulating the pH value with ammoniacal liquor is 4.0 ± 0.05)-tetrahydrofuran-acetonitrile (58: 12: 30)
Experimental procedure
Get each about 5mg of Atorvastatin calcium and intermediate impurity thereof, place the 100ml measuring bottle, add the thinning agent dissolving and be diluted to scale, shake up, as need testing solution.Get need testing solution, carry out high-efficient liquid phase analysis by above-mentioned condition, the record chromatogram the results are shown in Figure 1.
Retention time is that the chromatographic peak of 10.082min is the chromatographic peak of Atorvastatin calcium among Fig. 1, and the chromatographic peak of 17.997min is intermediate-1 chromatographic peak, and the chromatographic peak of 36.551min is starting material-0 chromatographic peak, is the chromatogram of Atorvastatin calcium among Fig. 2.The chromatographic peak degree of separation of Atorvastatin calcium and intermediate impurity thereof is good under these conditions, can satisfy the requirement of Chinese Pharmacopoeia.
Embodiment 2
Instrument and condition
Day island proper Tianjin LC-10ATVP pump, Tianjin, island SPD-10AVP ultraviolet-visible multiwavelength detector, RHEODYNE 7725i injector and TL9900 chromatographic data workstation, chromatographic column: cyano group post 250 * 4.6mm, 5 μ m, ultraviolet detection wavelength: 246nm, moving phase: 0.05mol/L ammonium citrate solution (regulating the pH value with ammoniacal liquor is 4.0 ± 0.05)-tetrahydrofuran-acetonitrile (58: 12: 30)
Experimental procedure
Get the about 5mg of Atorvastatin calcium, place the 10ml measuring bottle, add the thinning agent dissolving and be diluted to scale, shake up, as need testing solution.
Get test solution, carry out high-efficient liquid phase analysis according to above-mentioned condition, the record chromatogram the results are shown in Figure 3.
The atorvastatin calcium associated matters total impurities is less than 1.0% among Fig. 3, and the result shows the requirement that is up to state standards of the related substance of Atorvastatin calcium, and this law can be used for the quality monitoring of Atorvastatin calcium.
Instrument and condition
Day island proper Tianjin LC-10ATVP pump, Tianjin, island SPD-10AVP ultraviolet-visible multiwavelength detector, RHEODYNE 7725i injector and TL9900 chromatographic data workstation, chromatographic column: cyano group post 250 * 4.6mm, 5 μ m, ultraviolet detection wavelength: 246nm, moving phase: 0.05mol/L ammonium citrate solution (regulating the pH value with ammoniacal liquor is 3.5 ± 0.05)-tetrahydrofuran-acetonitrile (58: 12: 30)
Experimental procedure
Get each about 5mg of Atorvastatin calcium and intermediate impurity thereof, place the 100ml measuring bottle, add the thinning agent dissolving and be diluted to scale, shake up, as need testing solution, carry out high-efficient liquid phase analysis by above-mentioned condition, the record chromatogram the results are shown in Figure 4.
Fig. 4 proves that under the situation of pH value fine setting, Atorvastatin calcium still has good the separation with each intermediate, and this law can be used for the quality monitoring of Atorvastatin calcium.
Claims (7)
1. method with the high-performance liquid chromatogram determination atorvastatin calcium associated matters, it is characterized in that selecting for use cyano group silane key and silica gel is the chromatographic column of filler, with acetonitrile and tetrahydrofuran is organic phase, water be buffer salt as moving phase, can be used for Atorvastatin calcium and contain the quality control of the pharmaceutical composition of Atorvastatin calcium.
2. method according to claim 1 is characterized in that the organic phase in the moving phase is selected from acetonitrile, methyl alcohol, tetrahydrofuran.
3. method according to claim 1 is characterized in that the organic phase in the moving phase is acetonitrile and tetrahydrofuran, and the ratio of acetonitrile, tetrahydrofuran and water is: 30～40: 10～20: 50～70.
4. according to each described method of claim 1～3, it is characterized in that described water is a citrate buffer.
5. method according to claim 4 is characterized in that described phosphate is selected from wherein a kind of or potpourri of sodium citrate, ammonium citrate.
6. method according to claim 5 is characterized in that described citrate is an ammonium citrate.
7. according to each described method of claim 1～6, it is characterized in that selecting for use acetonitrile-0.05mol/L ammonium citrate solution (with ammoniacal liquor adjust pH to 7.4) (50: 50) to be the thinning agent dilute sample; It is an amount of to get Atorvastatin calcium, dissolve with thinning agent, be mixed with every 1ml and contain the sample solution of Atorvastatin calcium 1mg, flow velocity is 1ml/min, detects wavelength 246nm, selects the cyano group post for use, 25 ℃ of column temperatures, extracting sample solution 10ul injects high performance liquid chromatograph, finishes the mensuration of atorvastatin calcium associated matters.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102279241A (en) * | 2011-07-14 | 2011-12-14 | 北京汉典中西药研究开发中心 | Detection method of atorvastatin calcium capsule related substance |
| CN105136921A (en) * | 2015-08-14 | 2015-12-09 | 河南师范大学 | Method for measuring content of (4R,6R) -6-aminoethyl-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate |
| CN107102079A (en) * | 2017-04-26 | 2017-08-29 | 苏州海科医药技术有限公司 | Detect the application of Liquid Chromatography-Tandem Mass Spectrometry method and the clinical pharmacokinetics research of Atorvastatin and metabolin in human plasma |
| CN108373437A (en) * | 2018-04-08 | 2018-08-07 | 扬子江药业集团江苏海慈生物药业有限公司 | A kind of preparation method of Atorvastatin calcium isomers |
| CN109111436A (en) * | 2018-10-09 | 2019-01-01 | 河南师范大学 | A kind of impurity A, the separation method of impurity B and method that Impurity A content in Atorvastatin calcium condensation product is effectively reduced |
| CN109142586A (en) * | 2018-10-09 | 2019-01-04 | 河南师范大学 | A kind of method of liquid chromatography for measuring Atorvastatin calcium intermediate A TS-9 and its impurity B content |
| CN110646550A (en) * | 2018-06-26 | 2020-01-03 | 北京伟林恒昌医药科技有限公司 | Method for detecting related substances in atorvastatin calcium |
-
2009
- 2009-06-26 CN CN2009100877972A patent/CN101929985A/en active Pending
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| SANDEEP S. SONAWANE等: "Application of UV-Spectrophotometry and RP-HPLC for Simultaneous Determination of Atorvastatin Calcium and Ezetimibe in Pharmaceutical Dosage Form", 《EURASIAN JOURNAL OF ANALYTICAL CHEMISTRY》 * |
| SIDIKA ERTÜRK等: "An HPLC method for the determination of atorvastatin and its impurities in bulk drug and tablets", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》 * |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102279241A (en) * | 2011-07-14 | 2011-12-14 | 北京汉典中西药研究开发中心 | Detection method of atorvastatin calcium capsule related substance |
| CN102279241B (en) * | 2011-07-14 | 2013-05-29 | 北京汉典中西药研究开发中心 | Detection method of atorvastatin calcium capsule related substance |
| CN105136921A (en) * | 2015-08-14 | 2015-12-09 | 河南师范大学 | Method for measuring content of (4R,6R) -6-aminoethyl-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate |
| CN107102079A (en) * | 2017-04-26 | 2017-08-29 | 苏州海科医药技术有限公司 | Detect the application of Liquid Chromatography-Tandem Mass Spectrometry method and the clinical pharmacokinetics research of Atorvastatin and metabolin in human plasma |
| CN108373437A (en) * | 2018-04-08 | 2018-08-07 | 扬子江药业集团江苏海慈生物药业有限公司 | A kind of preparation method of Atorvastatin calcium isomers |
| CN110646550A (en) * | 2018-06-26 | 2020-01-03 | 北京伟林恒昌医药科技有限公司 | Method for detecting related substances in atorvastatin calcium |
| CN109111436A (en) * | 2018-10-09 | 2019-01-01 | 河南师范大学 | A kind of impurity A, the separation method of impurity B and method that Impurity A content in Atorvastatin calcium condensation product is effectively reduced |
| CN109142586A (en) * | 2018-10-09 | 2019-01-04 | 河南师范大学 | A kind of method of liquid chromatography for measuring Atorvastatin calcium intermediate A TS-9 and its impurity B content |
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Application publication date: 20101229 |