CN101858892B - Method for detecting landiolol hydrochloride optical isomers by high efficiency liquid chromatography - Google Patents
Method for detecting landiolol hydrochloride optical isomers by high efficiency liquid chromatography Download PDFInfo
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- CN101858892B CN101858892B CN 200910029421 CN200910029421A CN101858892B CN 101858892 B CN101858892 B CN 101858892B CN 200910029421 CN200910029421 CN 200910029421 CN 200910029421 A CN200910029421 A CN 200910029421A CN 101858892 B CN101858892 B CN 101858892B
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Abstract
The invention provides a method for detecting landiolol hydrochloride optical isomers by a high efficiency liquid chromatography, comprising the following steps: (1) configuring chromatographic conditions: a chromatographic column adopting silica gel the surface of which is coated with cellulose tris(4-methylbenzoate) is a fixed phase chiral column; a mobile phase is normal hexane-isopropanol-diethylamine; and the detection wave length is 200nm-240nm; (2) adopting organic solvent to prepare a sample into solution containing 0.5-5.0mg/ml of landiolol hydrochloride; and (3) determining and recording chromatogram. The separating degrees of landiolol hydrochloride and landiolol hydrochloride isomers A, B, C reached by the determination method of the invention can reach 1.5-3.9, which conforms to the requirement of Chinese pharmacopoeia. The method provided by the invention can be used for quantifying the landiolol hydrochloride optical isomers.
Description
Technical field
The present invention relates to detect by high performance liquid chromatography the method for hydrochloride landiolol (Landiolol Hydrochloride) optical isomer, say more specifically and detect in the hydrochloride landiolol production run or the method for Landiolol Hydrochloride Isomer A (Isomer A), Landiolol Hydrochloride Isomer B (Isomer B) and Landiolol Hydrochloride Isomer C (Isomer C) in the hydrochloride landiolol product.
Background technology
Hydrochloride landiolol is to carry out architecture advances on the esmolol hydrochloride basis and the noval chemical compound that obtains, its chemistry 4-[(2S by name)-and 2-hydroxyl-3-[[2-[(4-morpholine formyl) amino] ethyl] amino] propoxyl group] benzenpropanoic acid 4-[(4S)-2,2-dimethyl-1, the 3-dioxolane] methyl ester hydrochloride, molecular formula: C
25H
39N
3O
8HCl, molecular weight: 546.05, have selectivity β
1The receptor blocking effect does not have intrinsic sympathomimetic acitivity and membrane stabilizing action.The hydrochloride landiolol mechanism of action is that Main Function is in heart β
1Acceptor, and suppress the norepinephrine of SNE and adrenal medella release and the heart rate increase that adrenaline causes.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 method that detects gained hydrochloride landiolol A, B, C isomeride in the hydrochloride landiolol chirality is synthetic by high performance liquid chromatography, with the purity of control synthetic sample.
It is that fixedly the chiral column of phase detects that the present invention adopts Silica Surface to be coated with cellulose-three (4-methyl benzoic acid ester), and the hole in the cellulose esters class formation and passage and isomeride have optionally formed the isomeride inclusion compound, thereby reach separation.
Mobile phase all has a significant impact Landiolol Hydrochloride Isomer A, Landiolol Hydrochloride Isomer B and Landiolol Hydrochloride Isomer C degree of separation and peak shape in the experimental result, grope through inventor's experiment, determine with normal hexane-isopropyl alcohol-diethylamine (70～90: 10～30: 0.02～0.5, be preferably 75～85: 15～25: 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 hydrochloride landiolol, hydrochloride landiolol A, B, C isomer separation degree 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: methyl alcohol (50: 50) is solvent.
The actual conditions of the method that detects hydrochloride landiolol A, B, C isomeride by high performance liquid chromatography provided by the invention is as follows:
1. chromatographic condition: the chromatographic column adopting silica gel surface is coated with cellulose-three (4-methyl benzoic acid ester) and is the fixing chiral column of phase; Mobile phase is normal hexane-isopropyl alcohol-diethylamine (70～90: 10～30: 0.02～0.5, be preferably 75～85: 15～25: 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 20～40 ℃ (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: methyl alcohol (50: 50)), sample ligand is made as the solution of the solution (preferred 1～3mg/ml, more preferably 2mg/ml) of hydrochloric Landiolol 0.5～5.0mg/ml.
3. measure: solution is injected high performance liquid chromatograph, the record chromatogram, and analyze.
Adopt this chromatographic condition to measure that Landiolol Hydrochloride Isomer A, Landiolol Hydrochloride Isomer B and Landiolol Hydrochloride Isomer C degree of separation can reach 1.5～3.9 in hydrochloride landiolol, meet the Chinese Pharmacopoeia requirement.This chromatographic condition can be used for the quantitative of landiolol hydrochloride optical isomers simultaneously.
Description of drawings
Fig. 1: the high-efficient liquid phase chromatogram that separates hydrochloride landiolol, Landiolol Hydrochloride Isomer A, Landiolol Hydrochloride Isomer B and Landiolol Hydrochloride Isomer C according to the condition of embodiment 1.(1) number peak is Landiolol Hydrochloride Isomer B, and (2) number peak is Landiolol Hydrochloride Isomer A, and (3) number peak is Landiolol Hydrochloride Isomer C, and (4) number peak is hydrochloride landiolol
Fig. 2: the high-efficient liquid phase chromatogram that separates hydrochloride landiolol, Landiolol Hydrochloride Isomer A, Landiolol Hydrochloride Isomer B and Landiolol Hydrochloride Isomer C according to the condition of embodiment 2.(1) number peak is Landiolol Hydrochloride Isomer B, and (2) number peak is Landiolol Hydrochloride Isomer A, and (3) number peak is Landiolol Hydrochloride Isomer C, and (4) number peak is hydrochloride landiolol
Embodiment
Instrument: SHIMADZU LC-10AT high performance liquid chromatograph, SPD-10Avp UV-detector, OV-100 column oven;
Chromatographic column: Daicel Chralcel OJ-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 your A isomeride of the blue ground of hydrochloric acid, dissolves and be diluted to 2mg/ml with isopropyl alcohol-methyl alcohol (50: 50);
The preparation of location solution 2: it is an amount of that precision takes by weighing your B isomeride of the blue ground of hydrochloric acid, dissolves and be diluted to 2mg/ml with isopropyl alcohol-methyl alcohol (50: 50);
The preparation of location solution 3: it is an amount of that precision takes by weighing your C isomeride of the blue ground of hydrochloric acid, dissolves and be diluted to 2mg/ml with isopropyl alcohol-methyl alcohol (50: 50);
The preparation of sample solution: precision takes by weighing the blue ground of hydrochloric acid, and you are an amount of, dissolve and are diluted to 2mg/ml with isopropyl alcohol-methyl alcohol (50: 50);
Measure: respectively get location solution 1, location solution 2, location solution 3 and each 20 μ l of sample solution and inject high performance liquid chromatograph, the record chromatogram, spectrogram is seen Fig. 1.Hydrochloride landiolol, hydrochloride landiolol A, B, C isomer separation degree are 1.5-2.9.
Instrument: SHIMADZU LC-10AT high performance liquid chromatograph, SPD-10Avp UV-detector, OV-100 column oven;
Chromatographic column: AE.Lichrom OJ-H chromatographic column (0.46 * 25cm, 5 μ m);
Mobile phase: normal hexane-isopropyl alcohol-diethylamine (82: 18: 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 your A isomeride of the blue ground of hydrochloric acid, dissolves and be diluted to 2mg/ml with isopropyl alcohol-methyl alcohol (50: 50);
The preparation of location solution 2: it is an amount of that precision takes by weighing your B isomeride of the blue ground of hydrochloric acid, dissolves and be diluted to 2mg/ml with isopropyl alcohol-methyl alcohol (50: 50);
The preparation of location solution 3: it is an amount of that precision takes by weighing your C isomeride of the blue ground of hydrochloric acid, dissolves and be diluted to 2mg/ml with isopropyl alcohol-methyl alcohol (50: 50);
The preparation of sample solution: precision takes by weighing the blue ground of hydrochloric acid, and you are an amount of, dissolve and are diluted to 2mg/ml with isopropyl alcohol-methyl alcohol (50: 50);
Measure: respectively get location solution 1, location solution 2, location solution 3 and each 20 μ l of sample solution and inject high performance liquid chromatograph, the record chromatogram, spectrogram is seen Fig. 2.Hydrochloride landiolol, hydrochloride landiolol A, B, C isomer separation degree are 1.5-3.9.
Claims (12)
1. detect the method for landiolol hydrochloride optical isomers by high performance liquid chromatography, specific as follows:
1) chromatographic condition: the chromatographic column adopting silica gel surface is coated with cellulose-three (4-methyl benzoic acid ester) and is the fixing chiral column of phase; Mobile phase is normal hexane-isopropyl alcohol-diethylamine, and ratio is 70～90: 10～30: 0.02～0.5; The detection wavelength is 200nm～240nm; Column temperature is 20～40 ℃; Flow rate of mobile phase is 0.5～2.0ml/min;
2) preparation of sample solution: adopt organic solvent that sample ligand is made for the solution of hydrochloric Landiolol 0.5～5.0mg/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 75～85: 15～25: 0.05～0.2.
3. method according to claim 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. method according to claim 4, 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. method according to claim 6 is characterized in that column temperature is 35 ℃.
8. method according to claim 1 is characterized in that flow rate of mobile phase is 0.8～1.2ml/min.
9. method according to claim 8 is characterized in that flow rate of mobile phase is 1.0ml/min.
10. each described method is characterized in that the organic solvent that adopts in the preparation of sample solution is isopropyl alcohol-methyl alcohol according to claim 1-9, and ratio is 50: 50.
11. each described method according to claim 1-9 is characterized in that sample solution is formulated as the solution of hydrochloric Landiolol 1～3mg/ml.
12. method according to claim 11 is characterized in that sample solution is formulated as the solution of hydrochloric Landiolol 2mg/ml.
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| 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 |
| CN102183594B (en) * | 2011-02-23 | 2013-12-11 | 重庆植恩药业有限公司 | Method for detecting landiolol hydrochloride optical isomer |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101271085A (en) * | 2007-03-21 | 2008-09-24 | 北京德众万全药物技术开发有限公司 | Method for analytical separation of Landiolol Hydrochloride and its intermediate body by HPLC method |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101271085A (en) * | 2007-03-21 | 2008-09-24 | 北京德众万全药物技术开发有限公司 | Method for analytical separation of Landiolol Hydrochloride and its intermediate body by HPLC method |
Non-Patent Citations (3)
| Title |
|---|
| 童立年.注射用盐酸兰地洛尔的细菌内毒素检查法.《中国药业》.2008,第17卷(第24期),29. * |
| 赫冠男等.兰地洛尔的药理作用及其围手术期的应用.《中国新药与临床杂志》.2007,第26卷(第12期),942-945. * |
| 高雁 华.兰地洛尔预防拔管期应激反应的效果观察.《医学信息手术学分册》.2007,第20卷(第2期),155-156. * |
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Owner name: NANJING HICIN PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: HAICHEN PHARMACEUTICAL CO., LTD., NANJING |
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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 |