CN101271086A - HPLC method for analyzing and separating Trandolapril and impurity - Google Patents
HPLC method for analyzing and separating Trandolapril and impurity Download PDFInfo
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- CN101271086A CN101271086A CN 200710064574 CN200710064574A CN101271086A CN 101271086 A CN101271086 A CN 101271086A CN 200710064574 CN200710064574 CN 200710064574 CN 200710064574 A CN200710064574 A CN 200710064574A CN 101271086 A CN101271086 A CN 101271086A
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Abstract
The invention discloses a high-performance liquid chromatography method for analysis and separation of trandolapril bulk drug and impurities in a preparation thereof, which adopts an alkyl bonding chromatographic column and organic phase-buffer liquid as the mobile phase, thus rapidly analyzing the trandolapril bulk drug, intermediates introduced in the preparation and optical isomer impurities.
Description
Technical field
The invention belongs to the analytical chemistry field, relate to the analysis separation method of the impurity in RU-44570 bulk drug and the preparation thereof.The present invention is with intermediate of introducing in high performance liquid chromatography compartment analysis RU-44570 bulk drug and the preparation thereof and optical isomer impurity, the impurity that can analyze the RU-44570 bulk drug apace and contain the RU-44570 preparation with this method.
Background technology
RU-44570 is the angiotensin-converting enzyme inhibitor that does not contain sulfydryl, treatment essential hypertension and secondary hypertension disease.Its structural formula is:
The structural formula of its optical isomer impurity is:
The structural formula of its intermediate is respectively:
For the optical isomer impurity of RU-44570 and the intermediate of medicine building-up process, need carry out quality control.Realizing the compartment analysis of RU-44570 optical isomer impurity and intermediate, is the key of the RU-44570 bulk drug and quality of the pharmaceutical preparations control.
Finding through repetition test, use the C18 chromatographic column, is moving phase with the methyl alcohol-damping fluid of certain proportioning, the optical isomer impurity and the intermediate thereof of RU-44570 effectively can be separated, thereby can accurately control the quality of RU-44570 bulk drug and preparation.Method of the present invention can be simply, compartment analysis RU-44570 optical isomer impurity and its intermediate quickly and accurately.
Summary of the invention
The object of the present invention is to provide the efficient liquid-phase chromatography method of a kind of compartment analysis RU-44570 optical isomer impurity and its intermediate, thereby realize the separation determination of RU-44570 optical isomer impurity and intermediate thereof.
The said method of the present invention with high performance liquid chromatography compartment analysis RU-44570 optical isomer impurity and intermediate thereof, be that the employing octadecyl silane is the chromatographic column of filler, methyl alcohol-(it is moving phase that phosphate sodium dihydrogen buffer solution, phosphoric acid,diluted are transferred the organic phase-damping fluid of the extremely certain proportioning of pH.
Above-mentioned said chiral chromatographic column is selected from the C18 chromatographic column.
Organic phase of the present invention is selected from following compounds: methyl alcohol, acetonitrile.
Method of the present invention, the volume ratio of organic phase-damping fluid are 80: 20 (v/v)～60: 40 (v/v).
Above-mentioned said damping fluid is selected from phosphate buffer, and concentration is 0.01mol/L～0.05mol/L.
Method of the present invention, the pH scope of damping fluid is 2.5～4.
Method for separating and analyzing of the present invention, can realize in accordance with the following methods:
(1) get RU-44570 respectively, it is an amount of to reach each intermediate and optical isomer sample, places volumetric flask, uses dissolve with methanol, is mixed with every 1mL and contains RU-44570, the biased sample solution of optical isomer and each intermediate 0.2mg.
(2) flow rate of mobile phase being set is 1.0mL/min, and the detection wavelength is 208nm, and the chromatographic column column oven is a room temperature.
(3) the sample solution 10 μ L that get (1) inject liquid chromatograph, finish separating and analysis of RU-44570 and intermediate thereof and optical isomer.
Wherein:
High performance liquid chromatograph: Tianjin, island: LC-10ATvp, SPD-M10Avp,
Chromatographic column: the C18 (chromatographic column of 250mm * 4.6mm)
Moving phase: methyl alcohol-(0.01mol/L sodium dihydrogen phosphate, phosphoric acid,diluted is transferred pH to 2.5)=72: 28 (v/v).
Flow velocity: 1.0mL/min
Column temperature: room temperature
Detect wavelength: 208nm
Sampling volume: 10 μ L
The present invention adopts C18 (250mm * 4.6mm) chromatographic column, effectively compartment analysis RU-44570 intermediate and optical isomer thereof (impurity); Select the dissolve with methanol sample, guaranteed the stability of solution; Select sampling volume 10 μ L, column temperature is a room temperature, has improved the symmetry of chromatographic peak.The invention solves the bulk drug that contains RU-44570 intermediate and optical isomer thereof and the analysis and the separation problem of preparation, thereby guaranteed the quality controllable of RU-44570 bulk drug and preparation thereof.(the results are shown in accompanying drawing 1)
Description of drawings
Fig. 1 is the HPLC figure of condition most preferably
No. 1 peak is that 1, No. 2 peaks of intermediate are intermediate 2 and intermediate 4 among Fig. 1, No. 3 peaks are the RU-44570 main peak, No. 4 peaks are RU-44570 optical isomer (impurity) peak, No. 5 peaks are intermediate 3, can separate fully with its optical isomer impurity and 4 intermediates at many Pulis of this condition urine main peak as can be seen, and the RU-44570 main peak is about 8min.
Fig. 2 moving phase is the HPLC figure of acetonitrile-damping fluid=70: 30
No. 1 peak is that 1, No. 2 peaks of intermediate are intermediate 2 and intermediate 4 among Fig. 2, No. 3 peaks are the RU-44570 main peak, No. 4 peaks are RU-44570 optical isomer (impurity) peak, No. 5 peaks are intermediate 3, can separate fully with its optical isomer impurity and 4 intermediates at many Pulis of this condition urine main peak as can be seen, and the RU-44570 main peak is about 9min.
Fig. 3 moving phase is the HPLC figure of methyl alcohol-damping fluid=70: 30
No. 1 peak is that 1, No. 2 peaks of intermediate are intermediate 2 and intermediate 4 among Fig. 3, No. 3 peaks are the RU-44570 main peak, No. 4 peaks are RU-44570 optical isomer (impurity) peak, No. 5 peaks are intermediate 3, can separate fully with its optical isomer impurity and 4 intermediates at many Pulis of this condition urine main peak as can be seen, and the RU-44570 main peak is about 11min.
Fig. 4 damping fluid is the HPLC figure of pH4
No. 1 peak is that 1, No. 2 peaks of intermediate are intermediate 2 and intermediate 4 among Fig. 4, No. 3 peaks are the RU-44570 main peak, No. 4 peaks are RU-44570 optical isomer (impurity) peak, No. 5 peaks are intermediate 3, can separate fully with its optical isomer impurity and 4 intermediates at many Pulis of this condition urine main peak as can be seen, and the RU-44570 main peak is about 9min.
Fig. 5 ion concentration is the HPLC figure of 0.05mol/L
No. 1 peak is that 1, No. 2 peaks of intermediate are intermediate 2 and intermediate 4 among Fig. 5, No. 3 peaks are the RU-44570 main peak, No. 4 peaks are RU-44570 optical isomer (impurity) peak, No. 5 peaks are intermediate 3, can separate fully with its optical isomer impurity and 4 intermediates at many Pulis of this condition urine main peak as can be seen, and the RU-44570 main peak is about 8min.
Embodiment:
Instrument and condition
High performance liquid chromatograph: day island proper Tianjin: LC-10Avp, SPD-10Avp;
Chromatographic column: C18 (250mm * 4.6mm);
Moving phase: acetonitrile-(0.01mol/L sodium dihydrogen phosphate, phosphoric acid,diluted is transferred pH to 2.5)=60: 40
Flow velocity: 1.0mL/min;
Detect wavelength: 208nm;
Column temperature: room temperature;
Sampling volume: 10 μ L.
Experimental procedure
Take by weighing each 5mg of each intermediate and RU-44570 and optical isomer thereof respectively, place the 25mL volumetric flask, add moving phase dissolving and dilution and put scale, shake up, as biased sample solution.And take by weighing single intermediate and RU-44570 and each 5mg of optical isomer thereof respectively, and place 6 25mL volumetric flasks respectively, add moving phase dissolving and dilution and put scale, shake up, as qualitative contrast solution.
Get each contrast solution and biased sample solution respectively, carry out efficient liquid phase chromatographic analysis, the record chromatogram by above-mentioned condition.The results are shown in accompanying drawing 2, No. 1 peak is that 1, No. 2 peaks of intermediate are intermediate 2 and intermediate 4 among the figure, No. 3 peaks are the RU-44570 main peak, No. 4 peaks are RU-44570 optical isomer (impurity) peak, No. 5 peaks are intermediate 3, can separate fully with its optical isomer impurity and 4 intermediates at many Pulis of this condition urine main peak as can be seen, and the RU-44570 main peak is about 9min.
Instrument and condition
High performance liquid chromatograph: day island proper Tianjin: LC-10Avp, SPD-10Avp;
Chromatographic column: C18 (250mm * 4.6mm);
Moving phase: methyl alcohol-(0.01mol/L sodium dihydrogen phosphate, phosphoric acid,diluted is transferred pH to 2.5)=70: 30
Flow velocity: 1.0mL/min;
Detect wavelength: 208nm;
Column temperature: room temperature;
Sampling volume: 10 μ L.
Experimental procedure
Take by weighing each 5mg of each intermediate and RU-44570 and optical isomer thereof respectively, place the 25mL volumetric flask, add moving phase dissolving and dilution and put scale, shake up, as biased sample solution.And take by weighing single intermediate and RU-44570 and each 5mg of optical isomer thereof respectively, and place 6 25mL volumetric flasks respectively, add moving phase dissolving and dilution and put scale, shake up, as qualitative contrast solution.
Get each contrast solution and biased sample solution respectively, carry out efficient liquid phase chromatographic analysis, the record chromatogram by above-mentioned condition.The results are shown in accompanying drawing 3, No. 1 peak is that 1, No. 2 peaks of intermediate are intermediate 2 and intermediate 4 among the figure, No. 3 peaks are the RU-44570 main peak, No. 4 peaks are RU-44570 optical isomer (impurity) peak, No. 5 peaks are intermediate 3, can separate fully with its optical isomer impurity and 4 intermediates at many Pulis of this condition urine main peak as can be seen, and the RU-44570 main peak is about 11min.
Instrument and condition
High performance liquid chromatograph: day island proper Tianjin: LC-10Avp, SPD-10Avp;
Chromatographic column: C18 (250mm * 4.6mm);
Moving phase: methyl alcohol-(0.01mol/L sodium dihydrogen phosphate, phosphoric acid,diluted is transferred pH to 4)=75: 25
Flow velocity: 1.0mL/min;
Detect wavelength: 208nm;
Column temperature: room temperature;
Sampling volume: 10 μ L.
Experimental procedure
Take by weighing each 5mg of each intermediate and RU-44570 and optical isomer thereof respectively, place the 25mL volumetric flask, add moving phase dissolving and dilution and put scale, shake up, as biased sample solution.And take by weighing single intermediate and RU-44570 and each 5mg of optical isomer thereof respectively, and place 6 25mL volumetric flasks respectively, add moving phase dissolving and dilution and put scale, shake up, as qualitative contrast solution.
Get each contrast solution and biased sample solution respectively, carry out efficient liquid phase chromatographic analysis, the record chromatogram by above-mentioned condition.The results are shown in accompanying drawing 4, No. 1 peak is that 1, No. 2 peaks of intermediate are intermediate 2 and intermediate 4 among the figure, No. 3 peaks are the RU-44570 main peak, No. 4 peaks are RU-44570 optical isomer (impurity) peak, No. 5 peaks are intermediate 3, can separate fully with its optical isomer impurity and 4 intermediates at many Pulis of this condition urine main peak as can be seen, and the RU-44570 main peak is about 9min.
Instrument and condition
High performance liquid chromatograph: day island proper Tianjin: LC-10Avp, SPD-10Avp;
Chromatographic column: C18 (250mm * 4.6mm);
Moving phase: methyl alcohol-(0.05mol/L sodium dihydrogen phosphate, phosphoric acid,diluted is transferred pH to 2.5)=75: 25
Flow velocity: 1.0mL/min;
Detect wavelength: 208nm;
Column temperature: room temperature;
Sampling volume: 10 μ L.
Experimental procedure
Take by weighing each 5mg of each intermediate and RU-44570 and optical isomer thereof respectively, place the 25mL volumetric flask, add moving phase dissolving and dilution and put scale, shake up, as biased sample solution.And take by weighing single intermediate and RU-44570 and each 5mg of optical isomer thereof respectively, and place 6 25mL volumetric flasks respectively, add moving phase dissolving and dilution and put scale, shake up, as qualitative contrast solution.
Get each contrast solution and biased sample solution respectively, carry out efficient liquid phase chromatographic analysis, the record chromatogram by above-mentioned condition.The results are shown in accompanying drawing 5, No. 1 peak is that 1, No. 2 peaks of intermediate are intermediate 2 and intermediate 4 among the figure, No. 3 peaks are the RU-44570 main peak, No. 4 peaks are RU-44570 optical isomer (impurity) peak, No. 5 peaks are intermediate 3, can separate fully with its optical isomer impurity and 4 intermediates at many Pulis of this condition urine main peak as can be seen, and the RU-44570 main peak is about 8min.
Claims (8)
1. the high performance liquid chromatography of a compartment analysis RU-44570 is characterized in that adopting alkyl linked chromatographic column, and organic phase-damping fluid is a moving phase.
2. according to the described method of claim 1, it is characterized in that described alkyl linked chromatographic column, be selected from C8 chromatographic column and C18 chromatographic column, preferred C18 chromatographic column.
3. according to the described method of claim 1, it is characterized in that described organic phase is selected from methyl alcohol, acetonitrile, particular methanol.
4. according to the described method of claim 1, the proportional range that it is characterized in that described organic phase-damping fluid is 80: 20 (v/v)～60: 40 (v/v), preferred 75: 25 (v/v)～70: 30 (v/v), most preferably 72: 28 (v/v).
5. according to the described method of claim 1, it is characterized in that described damping fluid selection phosphate buffer and acetate buffer, preferably phosphoric acid salt buffer, most preferably phosphate sodium dihydrogen buffer solution.
6. according to the described method of claim 1, it is characterized in that selecting the pH scope of damping fluid is 2～4, preferred pH scope is 2～3, and most preferably pH 2.5.
7. according to the described method of claim 1, the concentration range of choice that it is characterized in that described damping fluid is 0.01mol/L～0.05mol/L, and preferred concentration is 0.01mol/L～0.02mol/L, and most preferable concentrations is 0.01mol/L.
8. according to the described method of claim 1, it is characterized in that: described method comprises following step:
(1) get RU-44570 respectively, it is an amount of to reach each intermediate and optical isomer sample, places volumetric flask,
Use dissolve with methanol, be mixed with certain density biased sample solution.
(2) flow rate of mobile phase being set is 0.4～1.2mL/min, and the detection wavelength is 208nm, and the chromatographic column column oven is a room temperature.
(3) the sample solution 2-50 μ L that gets (1) injects liquid chromatograph, finishes separating and analysis of RU-44570 and intermediate thereof and optical isomer.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200710064574 CN101271086B (en) | 2007-03-21 | 2007-03-21 | HPLC method for analyzing and separating Trandolapril and impurity |
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| CN 200710064574 CN101271086B (en) | 2007-03-21 | 2007-03-21 | HPLC method for analyzing and separating Trandolapril and impurity |
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| CN101271086A true CN101271086A (en) | 2008-09-24 |
| CN101271086B CN101271086B (en) | 2013-12-25 |
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Owner name: TAINZHOU WANSHENG PHARMTECH CO., LTD. Free format text: FORMER OWNER: DEZHONG WANQUAN PHARMACEUTICALS TECH. DEV. CO., LTD., BEIJING Effective date: 20140423 |
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Effective date of registration: 20140423 Address after: 225300 R12 Research Laboratory (Pharmaceutical city), Taizhou pharmaceutical hi tech Industrial Park, Jiangsu Province, China Patentee after: Taizhou Wanquan Pharm-tech Co., Ltd. Address before: 100097 Beijing city Haidian District Sijiqing Wanquan Zhuang 3 Building Patentee before: Dezhong Wanquan Pharmaceuticals Tech. Dev. Co., Ltd., Beijing |
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Effective date of registration: 20210201 Address after: 570314 no.279 Nanhai Avenue, Xiuying District, Haikou City, Hainan Province Patentee after: AVENTIS PHARMA (HAINAN) Co.,Ltd. Address before: 225300 R12 Research Office of Taizhou pharmaceutical high tech Industrial Park (Pharmaceutical city) Patentee before: TAINZHOU WANSHENG PHARMTECH Co.,Ltd. |