CN102703922A - Method for separating pantoprazole from tenatoprazole drug raceme - Google Patents
Method for separating pantoprazole from tenatoprazole drug raceme Download PDFInfo
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- CN102703922A CN102703922A CN2012101578109A CN201210157810A CN102703922A CN 102703922 A CN102703922 A CN 102703922A CN 2012101578109 A CN2012101578109 A CN 2012101578109A CN 201210157810 A CN201210157810 A CN 201210157810A CN 102703922 A CN102703922 A CN 102703922A
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Abstract
The invention discloses a method for separating pantoprazole from tenatoprazole drug raceme, and relates to a method for separating pantoprazole drugs. The method takes Cu(II) and L-histidine as chiral selectors and takes disodium hydrogen phosphate as background electrolyte, adopts ligand exchange capillary electrophoresis to ensure that the Cu(II), the L-histidine and pantoprazole drug raceme form ternary complex, then ensures that enantiomer is separated through a capillary electrophoresis apparatus, and adopts the ligand exchange capillary electrophoresis to separate two pantoprazole drug racemes, and the adopted chiral selector comprises the Cu(II) and the L-histidine. The method has high separation efficiency, is simple to operate, and comprises three links of sample processing, instrument preparing and sample handling; the chiral selector is low in cost and easy to obtain, and the amount of sample and reagent is small; and the background electrolyte does not contain organic solvent, is low in cost, and causes little environmental pollution. The method can be applied to in vivo analysis and product optical purity detection of the pantoprazole drugs, and simultaneously provides technical support and guarantee for the research and development of the chiral drugs.
Description
Technical field
The present invention relates to a kind of method of separate drug, particularly relate to a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme.
Background technology
Pantoprazole and TU-199 are one type of anti-ulcer medicaments, are mainly used in the diseases relevant with gastric acid secretion such as treatment duodenal ulcer, stomach ulcer, reflux esophagitis.By Fig. 1, Fig. 2 can know that pantoprazole and TU-199 are similar molecular, is the chiral drug of chiral centre with the sulphur atom, has R, two enantiomers of S.Have stereoselective medicine for major part, the raceme administration is equivalent to the administration simultaneously of two kinds of medicines, and impurity of the drug content 50% in other words, and therefore, the research and development of anti-ulcer medicament single enantiomer become focus.Because two enantiomorphs have similar physico-chemical property, conventional method is difficult to separate.At present chiral stationary phase HPLC and moving phase additive HPLC arranged to what this type of medicine chiral isolation analysis method had been reported.(Capillalry Electrophoresis CE) is grow up the eighties in 20th century one compartment analysis new technology efficiently to capillary electrophoresis.It is a motivating force with the high-voltage electric field, is split tunnel with the kapillary, realizes separating with the difference of distributing behavior according to the concentration between each component.It is celebrated with efficient, quick, easy; And clastotype is many, sample and reagent consumption is few, environmental pollution is little, cost is low; Can change the kind and the concentration of selective agent when the most important thing is optimized Separation flexibly, therefore more and more widely be applied to chiral separation.
Chiral ligand exchange chromatograph method (chiral ligand-exchange chromatography; CLEC); Promptly in chromatographic system, introduce certain metal ion species and certain chiral ligand; Can form two diastereomeric ternary complexes with enantiomorph to be measured, realize that through chromatographic process the stereoselectivity of optical isomer is separated.This method neither needs chiral stationary phase also not need pre-column derivatization, and addition is minimum in moving phase, and the chiral selector kind is various, so this method is convenient, fast, cost is low.At present, do not adopt chiral ligand exchange capillary electrophoresis to separate the report of this type of chipal compounds both at home and abroad.
Summary of the invention
The object of the present invention is to provide a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme; This method adopts CLEC; With Cu (II), the L-Histidine is a chiral selector, two anti-ulcer medicament racemies of compartment analysis; The body inner analysis and the optical purity of products that are used for this type of antiulcer agent chiral drug detect, for the research and development of this type of chiral drug provide technical support and guarantee.
The objective of the invention is to realize through following technical scheme:
A kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme; This method is made chiral selector with Cu (II) and L-Histidine; Sodium phosphate, dibasic is a background electrolytic solution; Utilization ligand exchange capillary electrophoresis makes Cu (II), L-Histidine and draws the azoles medicine to form ternary complex, makes raceme realize separating through HPCE then; Its utilization ligand exchange capillary electrophoresis separates two and draws the azole drug raceme, and used chiral selector is Cu (II) and L-Histidine;
Its concrete separating step is following:
A. the configuration of sample and running buffer: the configuration of sample stock solution, precision takes by weighing pantoprazole and TU-199 sample powder 10 mg respectively, puts in the brown volumetric flask of 10 mL; With dissolve with methanol and be settled to scale; Shake up, get the storing solution that each sample concentration is 1 mg/mL ,-20
oThe C refrigerator is preserved; Sample supplies the preparation of examination solution, and precision is measured each sample storing solution 1 mL respectively to the brown volumetric flask of 10 mL,, shake up to scale with methanol constant volume, 100 μ g/mL test liquids, 4
oThe C refrigerator is preserved; The preparation of running buffer 1; Take by weighing SODIUM PHOSPHATE, MONOBASIC, neutralized verdigris and L-Histidine 0.0195 g, 0.040 g, 0.0620 g successively and place 50 mL beakers; Add 25 mL second distillation water dissolution; Transfer to pH 5.0 with 0.1 mol/L sodium hydroxide solution and 10% phosphoric acid, promptly get running buffer, subsequent use behind 0.45 μ m filtering with microporous membrane; The preparation of running buffer 2; Take by weighing SODIUM PHOSPHATE, MONOBASIC, neutralized verdigris and L-Histidine 0.0195 g, 0.060 g, 0.0932 g successively and place 50 mL beakers; Add 25 mL second distillation water dissolution; Transfer to pH 5.0 with 0.1 mol/L sodium hydroxide solution and 10% phosphoric acid, promptly get running buffer, subsequent use behind 0.45 μ m filtering with microporous membrane.
B. instrument is prepared: sepn process is carried out in quartz capillary; Choose the kapillary of internal diameter 50 μ m; Intercepting one segment length 53 cm obtain detection window removing polyimide layer capillaceous apart from port 8 cm places, and new kapillary need wash and activation before use; During successive analysis, before each the analysis successively with 0.1 mol/LNaOH, redistilled water and running buffer respectively wash 10 min successively;
C., separation condition is set: pantoprazole: separation voltage 10 kV, detect wavelength 290 nm; TU-199: separation voltage 10 kV, detect wavelength 306 nm;
D. sample introduction: sample introduction height 10 cm, sample injection time 10 s, anodal sample introduction negative pole detects, between sample introduction with running buffer towards post 5 min, carry out sample introduction next time then.
Described a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme; The sample operation of azole drug raceme is drawn in its said separation: running buffer and sample are all through 0.45 μ m filtering with microporous membrane; And ultrasonic degas, sample is used dissolve with methanol, and 4 ℃ of refrigerators are preserved subsequent use.
Described a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme; The electrophoretic separation condition pantoprazole raceme of azole drug raceme is drawn in its said separation: running buffer: 5 mmol/L SODIUM PHOSPHATE, MONOBASICs contain 18 mmol/L L-Histidines, 6 mmol/L neutralized verdigriss, transfer to pH 5.0; Separation voltage: 10 kV; Ultraviolet detection wavelength: 290 nm; Electrophoretic separation condition TU-199 raceme: running buffer 5 mmol/L SODIUM PHOSPHATE, MONOBASICs contain 24 mmol/L L-Histidines, 12 mmol/L neutralized verdigriss, transfer to pH 5.0; Separation voltage: 15 kV; Ultraviolet detection wavelength: 306 nm.
Described a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme, the ligating atom that its said separation draws the azole drug raceme to be selected for use is Cu (II), and chiral ligand is the L-Histidine, and their coordination ratio are 1:2.
Described a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme, its said separation draw the instrument of azole drug raceme to prepare: kapillary length overall 53 cm, useful length 45 cm, internal diameter: 50 mm; New kapillary need wash and activation before use, during successive analysis, respectively washes 10 min with 0.1mol/LNaOH, redistilled water and running buffer successively before each the analysis; Between sample introduction with running buffer towards post 5 min, carry out sample introduction next time then.
Advantage of the present invention and effect are:
1. the present invention adopts the CLEC separation efficiency high, simple to operate, and back-ground electolyte does not contain organic solvent, and chiral selector kind and concentration flexibly changing, analysis cost are low, environmentally friendly, and the chiral selector consumption is few and cheap and easy to get.
2. the invention provides and separate two ligand exchange capillary electrophoresis that draw azole drug; Make chiral selector with Cu (II) and L-Histidine; Under suitable pH condition; Make Cu (II), L-Histidine respectively and draw left-handed, the dextrorotation of azoles medicine to form ternary complex; Separate through HPCE realization medicine raceme then, can be used for this type of body inner analysis that draws the azoles medicine and optical purity of products and detect, also technical support and guarantee are provided simultaneously for researching and developing this similar drug and single enantiomer administration.
Description of drawings
Fig. 1 is the pantoprazole structural formula;
Fig. 2 is a Tai Tuola azoles structural formula
Fig. 3 is that CLEC of the present invention separates pantoprazole raceme color atlas;
Fig. 4 is that CLEC of the present invention separates TU-199 raceme color atlas.
Embodiment
With reference to the accompanying drawings the present invention is elaborated.
Fig. 3 is that CLEC separates pantoprazole raceme color atlas, and two enantiomorph analysis times, separating size was greater than 1.5 in 25 min.
Fig. 4 is that CLEC separates TU-199 raceme color atlas, and two enantiomorph analysis times, separating size was greater than 1.5 in 25 min.
Embodiment one:
1. precision takes by weighing pantoprazole raceme 10 mg, puts in the brown volumetric flask of 10 mL, with dissolve with methanol and be settled to scale, shakes up.Get the storing solution that sample concentration is 1 mg/mL ,-20
oThe C refrigerator is preserved.Precision is measured sample storing solution 1 mL respectively to the brown volumetric flask of 10 mL,, shake up to scale with methanol constant volume, 100 μ g/mL test liquids, subsequent use behind 0.45 μ m filtering with microporous membrane.
2. prepare 5 mmol/LNaH
2PO
4Contain 8 mmol/L neutralized verdigriss and 16 mmol/LL-Histidines are made background electrolyte, use H
3PO
4Transfer to pH 5.0 with NaOH, through 0.45 μ m filtering with microporous membrane, and ultrasonic degas is subsequent use.Capillary column is walked baseline after respectively washing 10 min with 0.1 mol/LNaOH, redistilled water and above-mentioned running buffer successively; Treat that baseline steadily adopts siphon sample introduction, sample introduction height 10 cm, sample injection time 10 s in back (about 2 min); Anodal sample introduction negative pole detects, the record electrophorogram.Use redistilled water and running buffer respectively towards post 5 min between sample introduction successively, walk about baseline 2 min, advance next sample then.Separation voltage: 10 kV, ultraviolet detection wavelength: 290 nm.Separation electrophoresis figure such as Fig. 3, the pantoprazole raceme reaches baseline separation, and separating size is greater than 1.5.
Embodiment two:
1. precision takes by weighing TU-199 raceme 10 mg, in the brown volumetric flask of 10 mL, with dissolve with methanol and be settled to scale, shakes up.Get the storing solution that sample concentration is 1 mg/mL ,-20
oThe C refrigerator is preserved.Precision is measured in the brown volumetric flask of sample storing solution 1 mL to 10 mL,, shakes up to scale with methanol constant volume, gets 100 μ g/mL test liquids, and is subsequent use behind 0.45 μ m filtering with microporous membrane.
2. prepare 5 mmol/LNaH
2PO
4Contain 12 mmol/L neutralized verdigriss and 24 mmol/LL-Histidines are made running buffer, use H
3PO
4Transfer to pH 5.0 with NaOH, through 0.45 μ m filtering with microporous membrane, and ultrasonic degas is subsequent use.Capillary column is walked baseline after respectively washing 10 min with 0.1 mol/LNaOH, redistilled water and above-mentioned running buffer successively; Treat that baseline steadily adopts siphon sample introduction, sample introduction height 10 cm, sample injection time 10 s in back (about 2 min); Anodal sample introduction negative pole detects, the record electrophorogram.Use redistilled water and running buffer respectively towards post 5 min between sample introduction successively, walk about baseline 2 min, advance next sample then.Separation voltage: 15 kV, ultraviolet detection wavelength: 306 nm.Separation electrophoresis figure such as Fig. 4, the TU-199 raceme reaches baseline separation, and separating size is for 1.5.
Claims (5)
1. method of separating pantoprazole and Tai Tuola azoles medicine raceme; It is characterized in that; This method is made chiral selector with Cu (II) and L-Histidine, and Sodium phosphate, dibasic is a background electrolytic solution, utilization ligand exchange capillary electrophoresis; Make Cu (II), L-Histidine and draw azoles medicine raceme to form ternary complex; Make raceme realize separating through HPCE then, its utilization ligand exchange capillary electrophoresis separates two and draws the azole drug raceme, and used chiral selector is Cu (II) and L-Histidine;
Its concrete separating step is following:
A. the configuration of sample and running buffer: the configuration of sample stock solution, precision takes by weighing pantoprazole and TU-199 sample powder 10 mg respectively, puts in the brown volumetric flask of 10 mL; With dissolve with methanol and be settled to scale; Shake up, get the storing solution that each sample concentration is 1 mg/mL ,-20
oThe C refrigerator is preserved; Sample supplies the preparation of examination solution, and precision is measured each sample storing solution 1 mL respectively to the brown volumetric flask of 10 mL,, shake up to scale with methanol constant volume, 100 μ g/mL test liquids, 4
oThe C refrigerator is preserved; The preparation of running buffer 1; Take by weighing SODIUM PHOSPHATE, MONOBASIC, neutralized verdigris and L-Histidine 0.0195 g, 0.040 g, 0.0620 g successively and place 50 mL beakers; Add 25 mL second distillation water dissolution; Transfer to pH 5.0 with 0.1 mol/L sodium hydroxide solution and 10% phosphoric acid, promptly get running buffer, subsequent use behind 0.45 μ m filtering with microporous membrane; The preparation of running buffer 2; Take by weighing SODIUM PHOSPHATE, MONOBASIC, neutralized verdigris and L-Histidine 0.0195 g, 0.060 g, 0.0932 g successively and place 50 mL beakers; Add 25 mL second distillation water dissolution; Transfer to pH 5.0 with 0.1 mol/L sodium hydroxide solution and 10% phosphoric acid, promptly get running buffer, subsequent use behind 0.45 μ m filtering with microporous membrane;
B. instrument is prepared: sepn process is carried out in quartz capillary; Choose the kapillary of internal diameter 50 μ m; Intercepting one segment length 53 cm obtain detection window removing polyimide layer capillaceous apart from port 8 cm places, and new kapillary need wash and activation before use; During successive analysis, before each the analysis successively with 0.1 mol/LNaOH, redistilled water and running buffer respectively wash 10 min successively;
C., separation condition is set: pantoprazole: separation voltage 10 kV, detect wavelength 290 nm; TU-199: separation voltage 10 kV, detect wavelength 306 nm;
D. sample introduction: sample introduction height 10 cm, sample injection time 10 s, anodal sample introduction negative pole detects, between sample introduction with running buffer towards post 5 min, carry out sample introduction next time then.
2. a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme according to claim 1; It is characterized in that; The sample operation of azole drug raceme is drawn in said separation: running buffer and sample are all through 0.45 μ m filtering with microporous membrane; And ultrasonic degas, sample is used dissolve with methanol, and 4 ℃ of refrigerators are preserved subsequent use.
3. a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme according to claim 1; It is characterized in that; The electrophoretic separation condition pantoprazole raceme of azole drug raceme is drawn in said separation: running buffer: 5 mmol/L SODIUM PHOSPHATE, MONOBASICs contain 18 mmol/L L-Histidines, 6 mmol/L neutralized verdigriss, transfer to pH 5.0; Separation voltage: 10 kV; Ultraviolet detection wavelength: 290 nm; Electrophoretic separation condition TU-199 raceme: running buffer 5 mmol/L SODIUM PHOSPHATE, MONOBASICs contain 24 mmol/L L-Histidines, 12 mmol/L neutralized verdigriss, transfer to pH 5.0; Separation voltage: 15 kV; Ultraviolet detection wavelength: 306 nm.
4. a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme according to claim 1; It is characterized in that; The ligating atom that said separation draws the azole drug raceme to be selected for use is Cu (II), and chiral ligand is the L-Histidine, and their coordination ratio are 1:2.
5. a kind of method of separating pantoprazole and Tai Tuola azoles medicine raceme according to claim 1 is characterized in that, said separation draws the instrument of azole drug raceme to prepare: kapillary length overall 53 cm, useful length 45 cm, internal diameter: 50 mm; New kapillary need wash and activation before use, during successive analysis, respectively washes 10 min with 0.1mol/L NaOH, redistilled water and running buffer successively before each the analysis; Between sample introduction with running buffer towards post 5 min, carry out sample introduction next time then.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103063756A (en) * | 2012-11-29 | 2013-04-24 | 沈阳化工大学 | Method for separating antiulcer medicament by double-chiral selector capillary electrophoresis method |
| CN110508135A (en) * | 2019-07-16 | 2019-11-29 | 沈阳化工大学 | A kind of capillary electric chromatogram method separating Pantoprazole raceme |
| CN114486444A (en) * | 2022-02-07 | 2022-05-13 | 洛阳师范学院 | Capillary electrophoresis separation method of atenolol non-racemic mixture |
| CN115518415A (en) * | 2022-10-08 | 2022-12-27 | 沈阳化工大学 | Capillary electrochromatography method for separating pantoprazole racemate |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103063756A (en) * | 2012-11-29 | 2013-04-24 | 沈阳化工大学 | Method for separating antiulcer medicament by double-chiral selector capillary electrophoresis method |
| CN103063756B (en) * | 2012-11-29 | 2014-07-30 | 沈阳化工大学 | Method for separating antiulcer medicament by double-chiral selector capillary electrophoresis method |
| CN110508135A (en) * | 2019-07-16 | 2019-11-29 | 沈阳化工大学 | A kind of capillary electric chromatogram method separating Pantoprazole raceme |
| CN110508135B (en) * | 2019-07-16 | 2021-12-21 | 沈阳化工大学 | Capillary electrochromatography method for separating pantoprazole racemate |
| CN114486444A (en) * | 2022-02-07 | 2022-05-13 | 洛阳师范学院 | Capillary electrophoresis separation method of atenolol non-racemic mixture |
| CN114486444B (en) * | 2022-02-07 | 2024-02-20 | 洛阳师范学院 | Capillary electrophoresis separation method of atenolol non-racemate mixture |
| CN115518415A (en) * | 2022-10-08 | 2022-12-27 | 沈阳化工大学 | Capillary electrochromatography method for separating pantoprazole racemate |
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