CN101881755B - Method for detecting esmolol hydrochlorid optical isomer by high efficiency liquid chromatography - Google Patents
Method for detecting esmolol hydrochlorid optical isomer by high efficiency liquid chromatography Download PDFInfo
- Publication number
- CN101881755B CN101881755B CN 200910031294 CN200910031294A CN101881755B CN 101881755 B CN101881755 B CN 101881755B CN 200910031294 CN200910031294 CN 200910031294 CN 200910031294 A CN200910031294 A CN 200910031294A CN 101881755 B CN101881755 B CN 101881755B
- Authority
- CN
- China
- Prior art keywords
- esmolol
- hydrochlorid
- mobile phase
- optical isomer
- isopropyl alcohol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for detecting an esmolol hydrochlorid optical isomer by high efficiency liquid chromatography, which comprises the following steps: (1) the chromatographic conditions are as follows: a chromatographic column adopts cellulose esters as a chiral column of a stationary phase; a mobile phase is normal hexane-isopropanol-diethylamine; and a detecting wavelength is 200nm-240nm; (2) preparing a sample into a solution containing 0.1-2.0mg/mL esmolol hydrochlorid by an organic solvent; and (3) measuring and recording a chromatograph chart. The separation degrees of R-esmolol hydrochlorid and S-esmolol hydrochlorid in the measuring method of the invention are all higher than 1.5 and meet the requirement of Chinese Pharmacopoeia. The method provided by the invention can be simultaneously used for the quantification of the esmolol hydrochlorid optical isomer.
Description
Technical field
The present invention relates to detect by high performance liquid chromatography the method for esmolol hydrochloride (Esmolol Hydrochloride) optical isomer, say more specifically and detect in the esmolol hydrochlorid optical isomer production run or the method for (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride in the esmolol hydrochlorid optical isomer product.
Background technology
Esmolol hydrochloride has a chiral center, has 2 optical isomers, and its structural formula is respectively:
(S)-Esmolol Hydrochloride (R)-Esmolol Hydrochloride
Its chemical name is respectively 4-[(2S)-2-hydroxyl-3-(isopropylamino) propoxyl group] the methyl phenylpropionate hydrochloride, 4-[(2R)-and 2-hydroxyl-3-(isopropylamino) propoxyl group] the methyl phenylpropionate hydrochloride, molecular formula: C
16H
25NO
4HCl, molecular weight: 331.15.Esmolol hydrochloride is a kind of selectivity β of ultrashort effect
1-ARBs does not have intrinsic sympathomimetic acitivity and membrane stabilizing action.Its mechanism of action Main Function is in heart β
1Acceptor has the tranquillization of slowing down and exercise heart rate, reduces blood pressure, and reduces the effect of myocardial consumption of oxygen.The method that a lot of isomeride separate by high performance liquid chromatography is known, but the factors such as mobile phase, solvent, column temperature, chromatographic column have a significant impact for testing result or are not suitable for the target detection thing.
Summary of the invention
The purpose of this invention is to provide the optical isomer purity that detects gained sample in the esmolol hydrochlorid optical isomer chirality is synthetic by high performance liquid chromatography, with the quality of control finished product.
It is that the chiral column of fixedly phase detects that the present invention adopts cellulose esters, the formation of the hole in the cellulose esters class formation and passage and enantioselectivity the isomeride inclusion compound, thereby reach separation.
Mobile phase all has a significant impact (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride degree of separation and peak shape in the experimental result, grope through inventor's experiment, determine with normal hexane-isopropyl alcohol-diethylamine (70～98: 2～30: 0.02～0.5, be preferably 75～90: 10～25: 0.05～0.2, more preferably 80: 20: 0.1) be that the mobile phase effect is fine.Wherein add diethylamine and can improve peak shape.
The selection of solvent and (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride degree of separation are relevant.Determine to adopt n-propanol, isopropyl alcohol, ethanol, normal butyl alcohol, methyl alcohol to use solvent as dissolving through testing, preferably take isopropyl alcohol as solvent.
The actual conditions of the method that detects (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride by high performance liquid chromatography provided by the invention is as follows:
1. chromatographic condition: the chromatographic column adopting cellulose esters is the fixing chiral column of phase; Mobile phase is normal hexane-isopropyl alcohol-diethylamine (70～98: 2～30: 0.02～0.5, be preferably 75～90: 10～25: 0.05～0.2, more preferably 80: 20: 0.1); The detection wavelength is 200nm～240nm (being preferably 210nm～230nm, more preferably about 220nm); Column temperature is 20～45 ℃ (being preferably 30～40 ℃, more preferably 35 ℃); Flow rate of mobile phase is 0.5～2.0mL/min (being preferably 0.8～1.2mL/min, more preferably about 1.0mL/min).
2. the configuration of sample solution: adopt organic solvent (to be preferably selected from n-propanol, isopropyl alcohol, ethanol, normal butyl alcohol, methyl alcohol, isopropyl alcohol more preferably), sample ligand is made as the solution of the solution (preferred 0.5～2.0mg/mL, more preferably 1.0mg/mL) of hydrochloric esmolol optical isomer 0.1～2.0mg/mL.
3. measure: solution is injected high performance liquid chromatograph, the record chromatogram, and analyze.
Adopt this chromatographic condition to measure (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride degree of separation all above 1.5, meet the Chinese Pharmacopoeia requirement.This chromatographic condition can be used for the quantitative of esmolol hydrochlorid optical isomer simultaneously.
Description of drawings
Fig. 1: the high-efficient liquid phase chromatogram that separates (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride according to the condition of embodiment 1.
Fig. 2: the high-efficient liquid phase chromatogram that separates (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride according to the condition of embodiment 2.
Embodiment
Instrument: SHIMADZU LC-10AT high performance liquid chromatograph, SPD-10Avp UV-detector, OV-100 column oven;
Chromatographic column: CHIRAL CEL OD-H chromatographic column (0.46 * 25cm, 5 μ m);
Mobile phase: normal hexane-isopropyl alcohol-diethylamine (80: 20: 0.1)
Column temperature: 35 ℃
Flow velocity: 1.0mL/min
Detect wavelength: 220nm.
The preparation of location solution 1: it is an amount of that precision takes by weighing (R)-Esmolol Hydrochloride, with isopropyl alcohol dissolving and be diluted to 1.0mg/mL;
The preparation of location solution 2: it is an amount of that precision takes by weighing (S)-Esmolol Hydrochloride, with isopropyl alcohol dissolving and be diluted to 1.0mg/mL;
The preparation of biased sample solution: precision takes by weighing (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride is an amount of, dissolves and be diluted to isopropyl alcohol to contain (R)-Esmolol Hydrochloride, each 1.0mg/mL of (S)-Esmolol Hydrochloride;
Measure: respectively get location solution 1, location solution 2 and each 20 μ L of biased sample solution and inject high performance liquid chromatograph, the record chromatogram, spectrogram is seen Fig. 1.The degree of separation of (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride is 5.1.
Embodiment 2.
Instrument: SHIMADZU LC-10AT high performance liquid chromatograph, SPD-10Avp UV-detector, OV-100 column oven;
Chromatographic column: Sino-
OD chromatographic column (0.46 * 25cm, 5 μ m);
Mobile phase: normal hexane-isopropyl alcohol-diethylamine (85: 15: 0.1)
Column temperature: 35 ℃
Flow velocity: 1.0mL/min
Detect wavelength: 220nm.
The preparation of location solution 1: it is an amount of that precision takes by weighing (R)-Esmolol Hydrochloride, with isopropyl alcohol dissolving and be diluted to 1.0mg/mL;
The preparation of location solution 2: it is an amount of that precision takes by weighing (S)-Esmolol Hydrochloride, with isopropyl alcohol dissolving and be diluted to 1.0mg/mL;
The preparation of biased sample solution: precision takes by weighing (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride is an amount of, dissolves and be diluted to isopropyl alcohol to contain (R)-Esmolol Hydrochloride, each 1.0mg/mL of (S)-Esmolol Hydrochloride;
Measure: respectively get location solution 1, location solution 2 and each 20 μ L of biased sample solution and inject high performance liquid chromatograph, the record chromatogram, spectrogram is seen Fig. 2.The degree of separation of (R)-Esmolol Hydrochloride, (S)-Esmolol Hydrochloride is 4.9.
Claims (12)
1. detect the method for esmolol hydrochlorid optical isomer by high performance liquid chromatography, specific as follows:
1) chromatographic condition: the chromatographic column adopting cellulose esters is the fixing chiral column of phase; Mobile phase is normal hexane-isopropyl alcohol-diethylamine, and ratio is 70～98: 2～30: 0.02～0.5; The detection wavelength is 200nm～240nm; Column temperature is 20～45 ℃; Mobile phase ratio is 0.5～2.0mL/min;
2) preparation of sample solution: adopt organic solvent that sample ligand is made for the solution of hydrochloric esmolol 0.1～2.0mg/mL, described organic solvent is selected from n-propanol, isopropyl alcohol, ethanol, normal butyl alcohol, methyl alcohol;
3) measure: solution is injected high performance liquid chromatograph, and the record chromatogram is also analyzed.
2. method according to claim 1 is characterized in that described mobile phase normal hexane-isopropyl alcohol-diethylamine ratio is 75～90: 10～25: 0.05～0.2.
3. method according to claim 1 and 2 is characterized in that described mobile phase normal hexane-isopropyl alcohol-diethylamine ratio is 80: 20: 0.1.
4. method according to claim 1, it is characterized in that detecting wavelength is 210nm～230nm.
5. according to claim 1 or 4 described methods, it is characterized in that detecting wavelength is 220nm.
6. method according to claim 1 is characterized in that column temperature is 30～40 ℃.
7. according to claim 1 or 6 described methods, it is characterized in that column temperature is 35 ℃.
8. method according to claim 1 and 2 is characterized in that flow rate of mobile phase is 0.8～1.2mL/min.
9. according to claim 1 or 8 described methods, it is characterized in that flow rate of mobile phase is 1.0mL/min.
10. method according to claim 1 is characterized in that the organic solvent that adopts in the preparation of sample solution is isopropyl alcohol.
11. method according to claim 1 is characterized in that sample solution is formulated as the solution of hydrochloric esmolol optical isomer 0.5～2.0mg/mL.
12. method according to claim 11 is characterized in that sample solution is formulated as the solution of hydrochloric esmolol optical isomer 1.0mg/mL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910031294 CN101881755B (en) | 2009-05-04 | 2009-05-04 | Method for detecting esmolol hydrochlorid optical isomer by high efficiency liquid chromatography |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910031294 CN101881755B (en) | 2009-05-04 | 2009-05-04 | Method for detecting esmolol hydrochlorid optical isomer by high efficiency liquid chromatography |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101881755A CN101881755A (en) | 2010-11-10 |
| CN101881755B true CN101881755B (en) | 2013-05-29 |
Family
ID=43053818
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200910031294 Active CN101881755B (en) | 2009-05-04 | 2009-05-04 | Method for detecting esmolol hydrochlorid optical isomer by high efficiency liquid chromatography |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101881755B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102466659A (en) * | 2010-11-15 | 2012-05-23 | 天津药物研究院 | Method for detecting N-(N-benzoyl- phenylalanyl)-phenylalanine dipeptide derivative |
| BR112013018598A2 (en) | 2011-01-27 | 2016-10-18 | Baxter Healthcare Sa | pharmaceutical composition, method for treating heart disease, use of (s) -methyl-3- [4- (2-hydroxy-3- [4- (2-hydroxy-3-isopropylamino) propoxy] phenylpropionate, and method for control heart rate |
| CA2825311A1 (en) | 2011-01-27 | 2012-08-02 | Baxter International Inc. | Methods of treating tachycardia and/or controlling heart rate while minimizing and/or controlling hypotension |
-
2009
- 2009-05-04 CN CN 200910031294 patent/CN101881755B/en active Active
Non-Patent Citations (3)
| Title |
|---|
| 刘忠等.高效液相色谱法测定盐酸艾司洛尔的含量及其有关物质.《中国医院药学杂志》.2006,第26卷(第1期),104-106. * |
| 张莉.高效液相色谱法测定大鼠血清中艾司洛尔.《解放军药学学报》.2001,第17卷(第6期),330-331. * |
| 王贵发.顶空毛细管气相色谱法测定盐酸艾司洛尔有机溶剂残留量.《医药导报》.2008,第27卷(第5期),596-597. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101881755A (en) | 2010-11-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ali et al. | Polysaccharides chiral stationary phases in liquid chromatography | |
| CN104634887A (en) | Method for separating and measuring ticagrelor and optical isomer of ticagrelor | |
| Wei et al. | Enantioseparation of lomefloxacin hydrochloride by high-speed counter-current chromatography using sulfated-β-cyclodextrin as a chiral selector | |
| US9822089B2 (en) | R type of resveratrol dimer, preparation process therefor and purpose thereof in lowering blood sugar level | |
| CN101881755B (en) | Method for detecting esmolol hydrochlorid optical isomer by high efficiency liquid chromatography | |
| CN102706997A (en) | Detection method of fasudil hydrochloride-related substance | |
| CN103604895B (en) | Method for analytical separation of (-) benzoyl Corey lactone optical isomers by HPLC | |
| Hefnawy et al. | Enantioselective high-performance liquid chromatographic method for the determination of baclofen in human plasma | |
| Liu et al. | Use of various β-cyclodextrin derivatives as chiral selectors for the enantiomeric separation of higenamine by capillary electrophoresis | |
| CN105784878A (en) | Method for analyzing and separating cis-bicyclo[3,2,0]hept-2-ene-6-one enantiomer by HPLC (High Performance Liquid Chromatography) | |
| Zhou et al. | High performance liquid chromatographic separation of thirteen drugs collected in Chinese Pharmacopoeia 2010 (Ch. P2010) on cellulose ramification chiral stationary phase | |
| Lv et al. | Stereoselectiveseparation of racemic trans-paroxol, N-methylparoxetine and paroxetine containing two chiral carbon centres by countercurrent chromatography | |
| CN103760286A (en) | Method for measuring optical purity of solifenacin succinate intermediate by high-performance liquid chromatography | |
| CN101858892B (en) | Method for detecting landiolol hydrochloride optical isomers by high efficiency liquid chromatography | |
| CN102207494B (en) | Method for simultaneously determining four optical isomers of palonosetron hydrochloride | |
| Barbato et al. | Enantioselective retention of β-blocking agents on human serum albumin and α1-acid glycoprotein HPLC columns: Relationships with different scales of lipophilicity | |
| CN101706478A (en) | Method for testing isomer of palonosetron hydrochloride injection solution | |
| CN103512968B (en) | A kind of left nadifloxacin of liquid chromatography for separating and determining L-arginine and the method for optical isomer thereof | |
| CN101769902A (en) | Method for analyzing and separating optical isomer of pramipexole dihydrochloride by using HPLC method | |
| CN101609071A (en) | A kind of HPLC method analysis separates the method for ivabradine hydrochloride intermediate optical isomer | |
| CN112979511B (en) | Method for analyzing and preparing tert-butyl sulfinamide enantiomer by using HPLC | |
| CN103884783B (en) | A kind of analyzing detecting method of ivabradine midbody | |
| CN110398541B (en) | Method for separating and measuring maropiptan citrate and optical isomer thereof | |
| CN111351886B (en) | Method for determining impurity and main medicine content in phenol sulfoethylamine medicine | |
| CN102854261A (en) | Method for separating and detecting duloxetine and optical isomer of duloxetine through liquid chromatography |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: NANJING HICIN PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: HAICHEN PHARMACEUTICAL CO., LTD., NANJING |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 210046 Jiangsu province Nanjing HENGFA Nanjing economic and Technological Development Zone, Road No. 1 Patentee after: Nanjing hicin pharmaceutical Limited by Share Ltd Address before: 210046 Jiangsu province Nanjing HENGFA Nanjing economic and Technological Development Zone, Road No. 1 Patentee before: Haichen Pharmaceutical Co., Ltd., Nanjing |