CN107764922B - A kind of method for separating and detecting of Doxazosin optical isomer - Google Patents
A kind of method for separating and detecting of Doxazosin optical isomer Download PDFInfo
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- CN107764922B CN107764922B CN201710925724.0A CN201710925724A CN107764922B CN 107764922 B CN107764922 B CN 107764922B CN 201710925724 A CN201710925724 A CN 201710925724A CN 107764922 B CN107764922 B CN 107764922B
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Abstract
The invention discloses a kind of method for separating and detecting of Doxazosin optical isomer, using high performance liquid chromatography, with octadecylsilane chemically bonded silica (C18) for stationary phase, the organic phase of mobile phase is methanol, water phase is the biphosphate sodium water solution of pH value 3.4-3.6, also contain tetrahydrofuran or pyridine in organic phase or water phase, so that the total volume percentage composition of tetrahydrofuran and pyridine is 16-20% in mixed mobile phase, and the ratio between volumn concentration of tetrahydrofuran and pyridine is 3-5:1.Method provided by the invention can efficiently separate Doxazosin and its optical isomer by innovating in mobile phase, using only conventional C18 chromatographic column, economical and practical, easy to spread.
Description
Technical field
The invention belongs to drug fields, are related to the isomer impurities detection of Doxazosin, and in particular to a kind of Doxazosin
The method for separating and detecting of optical isomer.
Background technique
Doxazosin (Doxazosin, DS) is a kind of 1 receptor blocking pharmacon of new selective α, and there is apparent blood pressure lowering to make
With antihypertensive effect is that can improve microcirculation near or above other drugs for hypertension, the main feature of DS, can be with
Heart front and back load is reduced, can not only cause the expansion of resistance vessel, but also the expansion of capacity vessel can be caused, inhibit reflexively
Or slow down tachycardia；Another aspect DS has good improvement result to blood lipid metabolism, and certain beneficial effect is generated to blood lipid,
Also there is relaxation effect to atherosclerosis.The medicine is approved by the FDA in the United States to treat the first-line drug of hypertension.DS is as α 1
Receptor blocking pharmacon can also be used for the treatment of benign prostatic hyperplasis, and effect is rapidly, lasting, tolerance is good, is not likely to produce low blood pressure,
For DS there are also the effect for promoting prostatic cell apoptosis, reducing prostate, this is just more advantageous to the treatment of hyperplasia of prostate.
FDA has been approved by DS and Finasteride use in conjunction treats hyperplasia of prostate, merges prostate in old light, moderate hypertension and increases
In raw treatment, DS is not only safe and effective, but also has good tolerability.
For Doxazosin there are a chiral centre, the chemical structural formula of Doxazosin and its R type optical isomer is as follows:
Doxazosin is generally obtained by mesotomy, inevitable that R type optical isomer impurity.It is more to investigate
The quality of husky azoles piperazine product, it is necessary to establish the measuring method of R type optical isomer impurity in Doxazosin product.
Summary of the invention
The purpose of the present invention is to provide a kind of method for separating and detecting of Doxazosin optical isomer.
The present invention is achieved by following technical solution:
A kind of method of optical isomer impurity in separation detection Doxazosin, using high performance liquid chromatography, with 18
Alkyl silane bonded silica gel (C18) is stationary phase, and the organic phase of mobile phase is methanol, and water phase is the di(2-ethylhexyl)phosphate of pH value 3.4-3.6
In hydrogen sodium water solution, organic phase or water phase also contain tetrahydrofuran or pyridine so that in mixed mobile phase tetrahydrofuran and
The total volume percentage composition of pyridine is 16-20%, and the ratio between volumn concentration of tetrahydrofuran and pyridine is 3-5:1.
Preferably, organic phase is methanol-tetrahydrofuran-pyridine, the total volume hundred of tetrahydrofuran and pyridine in organic phase
Dividing content is 18%, and the ratio between the two volumn concentration is 4:1；Water phase is biphosphate sodium water solution-tetrahydro furan of pH value 3.5
It mutters-pyridine, the total volume percentage composition of tetrahydrofuran and pyridine in water phase is 18%, and the ratio between the two volumn concentration is 4:
1。
Preferably, the preparation method of the biphosphate sodium water solution of pH value 3.4-3.6 are as follows: first prepare the biphosphate of 40mM
Sodium water solution, then with phosphorus acid for adjusting pH value to 3.4-3.6.
Preferably, organic phase accounts for 52-56% in mobile phase.
Preferably, organic phase and water phase are according to volume ratio 54:46 isocratic elution.
Preferably, Detection wavelength 246nm.
Preferably, column temperature is 30 DEG C.
Preferably, flow rate of mobile phase 1mL/min.
Preferably, chromatographic column is octadecylsilane chemically bonded silica (C18) chromatographic column, and specification is long 250mm, internal diameter
4.6mm, 5 μm of packing material size.
Preferably, chromatographic column is ZORBAX Extend-C18.
Advantages of the present invention:
The prior art mostly uses Capillary Electrophoresis or chiral chromatogram post separation Doxazosin and its optical isomer, but hair
Cons electrophoresis poor repeatability is not suitable for quality control, and chiral chromatographic column is expensive, and service life is short, and cost is too high；This
The method provided is invented by innovating in mobile phase, using only conventional C18 chromatographic column can efficiently separate Doxazosin and
Its optical isomer, it is economical and practical, it is easy to spread.
Detailed description of the invention
Fig. 1 is the chemical structural formula of Doxazosin and its R type optical isomer；
Fig. 2 is the separating effect figure of 1 Doxazosin of embodiment and its optical isomer；
Fig. 3 is the separating effect figure of 2 Doxazosin of embodiment and its optical isomer；
Fig. 4 is the separating effect figure of 3 Doxazosin of embodiment and its optical isomer；
Fig. 5 is the separating effect figure of 4 Doxazosin of embodiment and its optical isomer；
Fig. 6 is the separating effect figure of 5 Doxazosin of embodiment and its optical isomer.
Specific embodiment
It is further described technical solution of the present invention combined with specific embodiments below.
The separation of 1 Doxazosin of embodiment and its optical isomer
One, experimental material
Shimadzu LC-20A high performance liquid chromatograph；
CPA225D electronic balance (Beijing Sai Duolisi instrument system Co., Ltd)；
Chromatographic column: ZORBAX Extend-C18 column (Agilent)；
Doxazosin and its optical isomer self-control, chemical structure and configuration are by confirmation, chemical structural formula such as Fig. 1 institute
Show；
Methanol, tetrahydrofuran are chromatographically pure, and water is liquid phase ultrapure water, remaining reagent is that analysis is pure.
Two, experimental method
1, mobile phase and test solution are prepared
Mobile phase A phase (organic phase): precision measures tetrahydrofuran 144mL, pyridine 36mL, with methanol constant volume to 1L.
Mobile phase B phase (water phase): the biphosphate sodium water solution of 40mM is first prepared, and with phosphorus acid for adjusting pH value to 3.5；So
It is accurate afterwards to measure tetrahydrofuran 144mL, pyridine 36mL, 1L is settled to the biphosphate sodium water solution of pH value 3.5.
The preparation of test solution: first precision weighs Doxazosin and its optical isomer, is then matched with flowing phased soln
The solution containing 0.5mg/mL Doxazosin, 0.5mg/mL optical isomer is made.
Doxazosin reference substance solution is prepared: first precision weighs Doxazosin, then is configured to contain with flowing phased soln
The solution of 0.1mg/mL Doxazosin.
Optical isomer reference substance solution prepare: precision weighs optical isomer, with flowing phased soln be configured to containing
The solution of 0.1mg/mL optical isomer.
2, high performance liquid chromatography parameter and sample introduction is analyzed
High performance liquid chromatograph: Shimadzu LC-20A high performance liquid chromatograph
Chromatographic column: Agilent ZORBAX Extend-C18 chromatographic column (250mm × 4.6mm, 5 μm)；
Mobile phase and type of elution: mobile phase A phase and B phase are according to volume ratio 54:46 isocratic elution；
Flow velocity: 1mL/min；
Column temperature: 30 DEG C；
Detection wavelength: 246nm；
Sample volume: 10 μ L.
Precision measures 10 μ L test solutions, reference substance solution injects liquid chromatograph, records chromatogram, observes sandy azoles
The separating effect of piperazine and its optical isomer calculates the separating degree of Doxazosin and its optical isomer.
Three, experimental result
The separating effect of Doxazosin and its optical isomer as shown in Fig. 2, under the chromatographic condition Doxazosin and its
Optical isomer can be separated preferably, and peak sequence is optical isomer, Doxazosin, and separating degree is greater than 1.5, reach baseline point
From.
The separation of 2 Doxazosin of embodiment and its optical isomer
Compared with Example 1, the volume ratio of tetrahydrofuran and pyridine in mobile phase A phase, B phase is only adjusted to 3:1, other
Method and parameter are completely the same.The separating effect of Doxazosin and its optical isomer is as shown in figure 3, more under the chromatographic condition
Husky azoles piperazine and its optical isomer can be separated preferably, and peak sequence is optical isomer, Doxazosin, and separating degree is greater than 1.5, reaches
To baseline separation.
The separation of 3 Doxazosin of embodiment and its optical isomer
Compared with Example 1, the volume ratio of tetrahydrofuran and pyridine in mobile phase A phase, B phase is only adjusted to 5:1, other
Method and parameter are completely the same.The separating effect of Doxazosin and its optical isomer is as shown in figure 4, more under the chromatographic condition
Husky azoles piperazine and its optical isomer can be separated preferably, and peak sequence is optical isomer, Doxazosin, and separating degree is greater than 1.5, reaches
To baseline separation.
4 comparative example of embodiment
Compared with Example 1, the volume ratio of tetrahydrofuran and pyridine in mobile phase A phase, B phase is only adjusted to 2:1, other
Method and parameter are completely the same.The separating effect of Doxazosin and its optical isomer is as shown in figure 5, more under the chromatographic condition
Husky azoles piperazine and its optical isomer can be separated preferably, and peak sequence is optical isomer, Doxazosin, and separating degree is greater than 1.5, reaches
To baseline separation.
5 comparative example of embodiment
Compared with Example 1, the volume ratio of tetrahydrofuran and pyridine in mobile phase A phase, B phase is only adjusted to 6:1, other
Method and parameter are completely the same.The separating effect of Doxazosin and its optical isomer is as shown in fig. 6, more under the chromatographic condition
Husky azoles piperazine and its optical isomer can be separated preferably, and peak sequence is optical isomer, Doxazosin, and separating degree is greater than 1.5, reaches
To baseline separation.
From above-described embodiment as can be seen that in the methods of the invention, the volume ratio of tetrahydrofuran and pyridine exists in mobile phase
Efficiently separating for Doxazosin and its optical isomer may be implemented within the scope of 3-5:1.
The prior art mostly uses Capillary Electrophoresis or chiral chromatogram post separation Doxazosin and its optical isomer, but hair
Cons electrophoresis poor repeatability is not suitable for quality control, and chiral chromatographic column is expensive, and service life is short, and cost is too high；This
The method provided is invented by innovating in mobile phase, using only conventional C18 chromatographic column can efficiently separate Doxazosin and
Its optical isomer, it is economical and practical, it is easy to spread.
Claims (8)
1. a kind of method of optical isomer impurity in separation detection Doxazosin, it is characterised in that: use high performance liquid chromatography
Method, using octadecylsilane chemically bonded silica as stationary phase, the organic phase of mobile phase is methanol, and water phase is the di(2-ethylhexyl)phosphate of pH value 3.5
In hydrogen sodium water solution, organic phase or water phase also contain tetrahydrofuran or pyridine so that in mixed mobile phase tetrahydrofuran and
The total volume percentage composition of pyridine is 18%, and the ratio between volumn concentration of tetrahydrofuran and pyridine is 4:1；
Organic phase and water phase are according to volume ratio 54:46 isocratic elution.
2. according to the method described in claim 1, it is characterized by: organic phase is methanol-tetrahydrofuran-pyridine, tetrahydrofuran
It is 18% with total volume percentage composition of the pyridine in organic phase, the ratio between the two volumn concentration is 4:1；Water phase is pH value 3.5
Biphosphate sodium water solution-tetrahydrofuran-pyridine, the total volume percentage composition of tetrahydrofuran and pyridine in water phase be 18%,
The ratio between the two volumn concentration is 4:1.
3. method according to claim 1 or 2, which is characterized in that the preparation side of the biphosphate sodium water solution of pH value 3.5
Method are as follows: first prepare the biphosphate sodium water solution of 40mM, then with phosphorus acid for adjusting pH value to 3.5.
4. according to the method described in claim 1, it is characterized by: Detection wavelength is 246nm.
5. according to the method described in claim 1, it is characterized by: column temperature is 30 DEG C.
6. according to the method described in claim 1, it is characterized by: flow rate of mobile phase is 1mL/min.
7. according to the method described in claim 1, it is characterized by: chromatographic column be octadecylsilane chemically bonded silica chromatographic column,
Specification be long 250mm, 4.6 mm of internal diameter, 5 μm of packing material size.
8. according to the method described in claim 7, it is characterized by: chromatographic column is ZORBAX Extend-C18.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1923205A (en) * | 2006-08-30 | 2007-03-07 | 任雷鸣 | Application of (-)doxazosin in preparing medicine for treating lower urinary tract symptom and bladder excessive activities diseases |
| CN100999519A (en) * | 2005-11-11 | 2007-07-18 | 华北制药集团新药研究开发有限责任公司 | (-) poly thaazoleazine methylsulfonate, its preparation process and use |
| CN107132297A (en) * | 2017-06-30 | 2017-09-05 | 南京普氟生物检测技术有限公司 | A kind of analyzing detecting method of pramiconazole optical isomer |
| CN107167546A (en) * | 2017-06-30 | 2017-09-15 | 南京普氟生物检测技术有限公司 | A kind of liquid phase analysis method for the Fluconazole optical isomer that ends |
| CN107167535A (en) * | 2017-07-20 | 2017-09-15 | 南京普氟生物检测技术有限公司 | A kind of method that reversed phase liquid chromatography detects Raltitrexed enantiomter |
-
2017
- 2017-10-05 CN CN201710925724.0A patent/CN107764922B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100999519A (en) * | 2005-11-11 | 2007-07-18 | 华北制药集团新药研究开发有限责任公司 | (-) poly thaazoleazine methylsulfonate, its preparation process and use |
| CN1923205A (en) * | 2006-08-30 | 2007-03-07 | 任雷鸣 | Application of (-)doxazosin in preparing medicine for treating lower urinary tract symptom and bladder excessive activities diseases |
| CN107132297A (en) * | 2017-06-30 | 2017-09-05 | 南京普氟生物检测技术有限公司 | A kind of analyzing detecting method of pramiconazole optical isomer |
| CN107167546A (en) * | 2017-06-30 | 2017-09-15 | 南京普氟生物检测技术有限公司 | A kind of liquid phase analysis method for the Fluconazole optical isomer that ends |
| CN107167535A (en) * | 2017-07-20 | 2017-09-15 | 南京普氟生物检测技术有限公司 | A kind of method that reversed phase liquid chromatography detects Raltitrexed enantiomter |
Non-Patent Citations (4)
| Title |
|---|
| Chiral Recognition in Liquid Chromatography Utilising Chargeable Cyclodextrins for Resolution of Doxazosin Enantiomers;PAUL K. OWENS et al.;《CHIRALITY》;19971231;第9卷;184-190页 |
| 反相高效液相色谱法测定血浆中多沙唑嗪;陈志琼 等;《西南师范大学学报（自然科学版）》;20051231;第30卷;1066-1069 |
| 多沙唑嗪中间体的手性分离方法优化研究;陈志琼 等;《精细化工》;20070131;第24卷;101-104页 |
| 多沙唑嗪手性及非手性液相分析方法的建立和应用研究;甄亚钦;《万方数据知识服务平台》;20141014;全文 |
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