CN102297911A - High efficiency liquid chromatography method for separating blonanserin intermediate III from other intermediates - Google Patents
High efficiency liquid chromatography method for separating blonanserin intermediate III from other intermediates Download PDFInfo
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- CN102297911A CN102297911A CN2011101960974A CN201110196097A CN102297911A CN 102297911 A CN102297911 A CN 102297911A CN 2011101960974 A CN2011101960974 A CN 2011101960974A CN 201110196097 A CN201110196097 A CN 201110196097A CN 102297911 A CN102297911 A CN 102297911A
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- intermediate iii
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Abstract
The invention discloses a high efficiency liquid chromatography method for separating blonanserin intermediate III from other intermediates. According to the method, a chromatographic column (250mm*4.6mm, 5mum) with octane silicane bonded silica gel as a filling agent is adopted; buffering solutions and organic modifiers with different proportions are adopted as mobile phases; and blonanserin intermediate III is rapidly separated from other intermediate impurities under normal temperature.
Description
?
Technical field
The invention belongs to and relate to a kind of high performance liquid chromatography, the high performance liquid chromatography separation method of especially a kind of blonanserin intermediate III and other intermediate.
Background technology
Blonanserin is a kind of anti-psychotropic agent, atypical anti-psychotropic agent, and compare the spinoff reaction with other anti-psychotropic agents few.Intermediate III molecular formula: C
17H
18OFN, chemistry (Z)-4-(4-fluorophenyl)-5,6,7,8 by name, 910-six hydrogen cyclooctane are [b] pyridine-2 (1H)-ketone also, needs the intermediate compound I of separation, and intermediate II, intermediate III structural formula are respectively:
Intermediate I
Intermediate II
Intermediate III
In order effectively to separate blonanserin intermediate III and other intermediate, accurately control the quality of blonanserin intermediate III, present also do not have a kind of high performance liquid chromatogram isocratic elution mode to realize effectively separating of blonanserin intermediate III and other intermediate.
Summary of the invention
The high performance liquid chromatography separation method that the purpose of this invention is to provide a kind of blonanserin intermediate III and other intermediate, be implemented in the needs of its intermediate purity of control in the process of leading to the synthesising target compound blonanserin, thereby reach accurate control the blonanserin quality.
A kind of blonanserin intermediate III that the present invention relates to and the high performance liquid chromatogram separation method of other intermediate may further comprise the steps:
(1) it is an amount of to get the blonanserin sample, with organic solvent dissolution blonanserin sample, is mixed with every 1ml and contains
The sample solution of blonanserin 0.5mg～1.0mg;
(2) moving phase of liquid chromatograph is set, promptly the A pump is an organic modifiers, and the B pump is a buffer solution, stream
Moving phase: the volume ratio of buffer solution and organic modifiers is 55:45;
(3) the flow rate of mobile phase 0.6～1.2mL/min of liquid chromatograph is set, detects wavelength 224 ± 3nm,
And 20 ℃～40 ℃ of the column ovens that the liquid chromatograph chromatographic column is set;
(4) the sample solution 5-20 μ l that gets step (1) injects the liquid chromatograph that is provided with through step (2) (3), finishes
The blonanserin intermediate III is separated with other intermediate.
Further, the organic solvent of described step (1) is methyl alcohol or ethanol.
The flow velocity of described step (3) is 0.6～1.2mL/min, detects wavelength 224 ± 3nm.
It is the chromatographic column of filling agent that described liquid chromatograph adopts octane silane key and silica gel, the specification of chromatographic column
Be length 250mm, internal diameter 4.6mm, granularity 5 μ m.
The organic modifiers of described step (2) is acetonitrile or methyl alcohol.
The buffer solution of described step (2) is 0.1% phosphoric acid water or aqueous phosphatic.
It is the chromatographic column of filling agent that the present invention adopts octane silane key and silica gel, can effectively analyze and separate blonanserin intermediate III and other intermediate; Selection methyl alcohol is solvent, guarantees that sample can dissolve fully; Select sampling volume 10 μ L, improved the symmetry of chromatographic peak; Select flow velocity 1.0mL/min, can improve degree of separation; Selecting moving phase is organic modifiers acetonitrile and buffering solution 0.1% phosphoric acid water, realization blonanserin intermediate III is separated fully with other intermediate, thereby guaranteed the quality controllable of blonanserin intermediate and preparation thereof, realized the quality control of blonanserin intermediate and preparation production run synthetic at the blonanserin medicine.
Description of drawings
Fig. 1 is embodiment 1 high-efficient liquid phase chromatogram;
Fig. 2 is embodiment 2 high-efficient liquid phase chromatograms;
Fig. 3 is embodiment 3 high-efficient liquid phase chromatograms.
Embodiment
Embodiment 1
Adopting Tianjin, island LC-20AT model high performance liquid chromatograph, Welch Materials brand octane silane key and silica gel is the chromatographic column of filling agent, and the specification of chromatographic column is length 250mm, internal diameter 4.6mm, granularity 5 μ m.
The high performance liquid chromatogram separation method of a kind of blonanserin intermediate III and other intermediate may further comprise the steps:
(1) gets blonanserin intermediate III and intermediate I, each 5mg of II respectively, place the 10mL volumetric flask, add dissolve with methanol and be diluted to scale, shake up, as need testing solution;
(2) moving phase of liquid chromatograph is set, promptly the A pump is an organic modifiers, and the B pump is a buffer solution, moving phase: the volume ratio of 0.1% phosphoric acid water and methyl alcohol is 55:45
(3) flow rate of mobile phase 0.6mL/min, the detection wavelength 223nm of liquid chromatograph are set, and liquid is set
20 ℃ of the column ovens of chromatography chromatographic column;
(4) the need testing solution 20 μ l that get step (1) inject the liquid chromatograph that is provided with through step (2) (3), finish separating of blonanserin intermediate III and other intermediate, and the record chromatogram the results are shown in accompanying drawing 1.
Retention time is the chromatographic peak that the chromatographic peak of 7.155min, 8.301min is respectively intermediate II, I among Fig. 1, and retention time is that 13.388min is the chromatographic peak of blonanserin intermediate III.The degree of separation of intermediate II and intermediate III reaches 15, meets fully that " 2010 editions Chinese pharmacopoeia degree of separation are not less than 1.5 regulation, show that blonanserin intermediate III can be issued to well at same chromatographic condition with other intermediate to separate.
Embodiment 2
Adopting Tianjin, island LC-20AT model high performance liquid chromatograph, Welch Materials brand octane silane key and silica gel is the chromatographic column of filling agent, and the specification of chromatographic column is length 250mm, internal diameter 4.6mm, granularity 5 μ m.
The high performance liquid chromatogram separation method of a kind of blonanserin intermediate III and other intermediate may further comprise the steps:
(1) gets blonanserin intermediate III and intermediate I, each 8mg of II respectively, place the 10mL volumetric flask, add dissolve with methanol and be diluted to scale, shake up, as need testing solution;
(2) moving phase of liquid chromatograph is set, promptly the A pump is an organic modifiers, and the B pump is a buffer solution, moving phase: the volume ratio of 0.1% phosphoric acid water and acetonitrile is 50:50
(3) flow rate of mobile phase 1.2mL/min, the detection wavelength 227nm of liquid chromatograph are set, and liquid is set
40 ℃ of the column ovens of chromatography chromatographic column;
(4) the need testing solution 5 μ l that get step (1) inject the liquid chromatograph that is provided with through step (2) (3), finish separating of blonanserin intermediate III and other intermediate, and the record chromatogram the results are shown in accompanying drawing 2.
Retention time is the chromatographic peak that the chromatographic peak of 5.970min, 6.898min is respectively intermediate II, I among Fig. 2, and retention time is that 9.605min is the chromatographic peak of blonanserin intermediate III.The degree of separation of intermediate II and intermediate III reaches 12, meets fully that " 2010 editions Chinese pharmacopoeia degree of separation are not less than 1.5 regulation, show that blonanserin intermediate III can be issued to well at same chromatographic condition with other intermediate to separate.
Embodiment 3
Adopting Tianjin, island LC-20AT model high performance liquid chromatograph, Welch Materials brand octane silane key and silica gel is the chromatographic column of filling agent, and the specification of chromatographic column is length 250mm, internal diameter 4.6mm, granularity 5 μ m.
The high performance liquid chromatogram separation method of a kind of blonanserin intermediate III and other intermediate may further comprise the steps:
(1) gets blonanserin intermediate III and intermediate I, each 10mg of II respectively, place the 10mL volumetric flask, add dissolve with methanol and be diluted to scale, shake up, as need testing solution;
(2) moving phase of liquid chromatograph is set, promptly the A pump is an organic modifiers, and the B pump is a buffer solution, and the volume ratio of moving phase 0.1% phosphoric acid water and acetonitrile is 55:45
(3) flow rate of mobile phase 1.2mL/min, the detection wavelength 227nm of liquid chromatograph are set, and liquid is set
25 ℃ of the column ovens of chromatography chromatographic column;
(4) the need testing solution 10 μ l that get step (1) inject the liquid chromatograph that is provided with through step (2) (3), finish separating of blonanserin intermediate III and other intermediate, and the record chromatogram the results are shown in accompanying drawing 3.
Retention time is the chromatographic peak that the chromatographic peak of 6.737min, 7.727min is respectively intermediate II, I among Fig. 3, and retention time is that 11.310min is the chromatographic peak of blonanserin intermediate III.The degree of separation of intermediate II and intermediate III reaches 16, meets fully that " 2010 editions Chinese pharmacopoeia degree of separation are not less than 1.5 regulation, show that blonanserin intermediate III can be issued to well at same chromatographic condition with other intermediate to separate.
Claims (6)
1. the high performance liquid chromatogram separation method of a blonanserin intermediate III and other intermediate may further comprise the steps:
(1) it is an amount of to get the blonanserin sample, with organic solvent dissolution blonanserin sample, is mixed with every 1ml and contains cloth south
The sample solution of look woods 0.5mg～1.0mg;
(2) moving phase of liquid chromatograph is set, promptly the A pump is an organic modifiers, and the B pump is a buffer solution, moving phase:
The volume ratio of buffer solution and organic modifiers is 55:45;
(3) the flow rate of mobile phase 0.6～1.2mL/min of liquid chromatograph is set, detects wavelength 224 ± 3nm, and
20 ℃～40 ℃ of the column ovens of liquid chromatograph chromatographic column are set;
(4) the sample solution 5-20 μ l that gets step (1) injects the liquid chromatograph that is provided with through step (2) (3), finishes cloth south
Look woods intermediate III is separated with other intermediate.
2. a kind of blonanserin intermediate III according to claim 1 is separated with the high performance liquid chromatogram of other intermediate
Method is characterized in that: the organic solvent of described step (1) is methyl alcohol or ethanol.
3. a kind of blonanserin intermediate III according to claim 1 is separated with the high performance liquid chromatogram of other intermediate
Method is characterized in that: the flow velocity of described step (3) is 0.6～1.2mL/min, detects wavelength 224 ± 3nm.
4. a kind of blonanserin intermediate III according to claim 1 is separated with the high performance liquid chromatogram of other intermediate
Method is characterized in that: it is the chromatographic column of filling agent that described liquid chromatograph adopts octane silane key and silica gel,
The specification of chromatographic column is length 250mm, internal diameter 4.6mm, granularity 5 μ m.
5. a kind of blonanserin intermediate III according to claim 1 is separated with the high performance liquid chromatogram of other intermediate
Method is characterized in that: the organic modifiers of described step (2) is acetonitrile or methyl alcohol.
6. a kind of blonanserin intermediate III according to claim 1 is separated with the high performance liquid chromatogram of other intermediate
Method is characterized in that: the buffer solution of described step (2) is 0.1% phosphoric acid water or aqueous phosphatic.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101747273A (en) * | 2008-12-02 | 2010-06-23 | 浙江华海药业股份有限公司 | Preparing method of blonanserin intermediate |
| CN102093289A (en) * | 2010-10-29 | 2011-06-15 | 常州华生制药有限公司 | New preparation method of Blonanserin intermediate |
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2011
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101747273A (en) * | 2008-12-02 | 2010-06-23 | 浙江华海药业股份有限公司 | Preparing method of blonanserin intermediate |
| CN102093289A (en) * | 2010-10-29 | 2011-06-15 | 常州华生制药有限公司 | New preparation method of Blonanserin intermediate |
Non-Patent Citations (1)
| Title |
|---|
| 朱彩燕等: "HPLC法测定布南色林片的含量", 《中国药师》, vol. 13, no. 10, 31 December 2010 (2010-12-31), pages 1473 - 1474 * |
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