CN103018354A

CN103018354A - Chiral separation analyzing method of antiulcer medicament

Info

Publication number: CN103018354A
Application number: CN201210484144XA
Authority: CN
Inventors: 关瑾; 阎峰; 石爽; 王思林
Original assignee: Shenyang University of Chemical Technology
Current assignee: Shenyang University of Chemical Technology
Priority date: 2012-11-26
Filing date: 2012-11-26
Publication date: 2013-04-03

Abstract

The invention provides a chiral separation analyzing method of an antiulcer medicament, relates to a chemical analyzing method, and in particular relates to a capillary electrophoresis chiral separation analyzing method of four antiulcer medicaments. The method comprises a sample preparation step and a CLEC (chiral ligand-exchange chromatography) separation condition setting step. The CLEC separation condition comprises the steps of regulating the pH to be 7.0 and the content of acetonitrile to be 25 percent on a Diamonsil C18 chromatographic column with L-histidine with mobile phase of 1mmol/L and copper acetate with mobile phase of 0.05mmol/L, and balancing for 60 minutes; and feeding 5mu L of 0.5mg/mL testing liquid, wherein the ultraviolet detection wavelength is 290nm. By adopting CLEC, the method is simple in operation and low in cost, can be used for in vivo analysis and optical purity detection of antiulcer chiral medicaments, and provides technical guarantee to researches and development of chiral medicaments.

Description

A kind of chiral isolation analysis method of anti-ulcer medicament

Technical field

The present invention relates to a kind of chemical analysis method, particularly relate to a kind of chiral isolation analysis method of anti-ulcer medicament.

Background technology

Chiral ligand exchange chromatograph method (chiral ligand-exchange chromatography, CLEC), namely 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.The method neither needs chiral stationary phase also not need pre-column derivatization, and addition is minimum in mobile phase, so the method is convenient, fast and cost is low.At present, do not adopt the chiral ligand exchange chromatograph method to separate the report that contains the sulfoxide radicals chipal compounds both at home and abroad.

Four anti-ulcer medicament is that proton pump inhibitor (PPIs) comprises Omeprazole, Pantoprazole, Lansoprazole and Rabeprazole.PPIs is mainly used in treating the diseases relevant with gastric acid secretion such as duodenal ulcer, gastric ulcer, reflux esophagitis.PPIs has similar molecular structure, has a chiral sulfur atom center in the molecule, has R, two enantiomters of S, and clinical form mainly with raceme is used.At present, only has Omeprazole levo form-esomprazole (trade name: anti-letter) in U.S.'s listing, become in the world the most salable anti-ulcer agent in this type of medicine.Research and development to this type of anti-ulcer medicament single enantiomer have become focus.Because two enantiomorphs have similar physicochemical property, conventional method is difficult to separate, and at present this type of medicine chiral isolation analysis method is mainly adopted the Chiral stationary phase liquid chromatography method.

Summary of the invention

The object of the present invention is to provide a kind of chiral isolation analysis method of anti-ulcer medicament, adopt CLEC, with Cu (II), L-Histidine is chiral selector, compartment analysis four anti-ulcer medicament enantiomorph.The body inner analysis and the optical purity of products that are used for this type of antiulcer chiral drug detect, for the research and development of this type of chirality medicine provide technical guarantee.

The objective of the invention is to be achieved through the following technical solutions:

A kind of chiral isolation analysis method of anti-ulcer medicament is the method for four anti-ulcer medicament capillary pipe electrophoresis chiral separation analysis, and described method comprises the sample configuration and chromatographic separation condition is set:

A. sample configuration: 0.5 mg/mL sample solution configures with 0.1M NaOH;

B., chromatographic separation condition is set: the separation chromatography post, mobile phase composition, flow velocity, sampling volume detects wavelength;

The chiral isolation analysis method of described a kind of anti-ulcer medicament, described chromatographic separation condition comprises: chromatographic column: Dikma Diamonsil C ₁₈, be 150 mm * 4.6 mm I.D., 5 μ m; Mobile phase: 1 mmol/L L-Histidine, 0.5 mmol/L Schweinfurt green, pH 7.0 and 25% acetonitrile, ultrasonic degas behind the membrane filtration of 0.45 μ m then, change mobile phase needs balance 60 min at every turn; Detect wavelength: 290 nm; Flow velocity: 1.0 ml/mL; Sample size: 5 μ L.

Advantage of the present invention and effect are:

The present invention adopts that CLEC is simple to operate, cost is low, and body inner analysis and the optical purity that can be used for this type of antiulcer chiral drug detect, for the research and development of this type of chirality medicine provide technical guarantee.

Description of drawings

Fig. 1 is that CLEC of the present invention separates the omeprazole enantiomer chromatogram;

Fig. 2 is that CLEC of the present invention separates the pantoprazole enantiomers chromatogram;

Fig. 3 is that CLEC of the present invention separates Lansoprazole enantiomorph chromatogram;

Fig. 4 is that CLEC of the present invention separates Rabeprazole enantiomorph chromatogram.

Embodiment

The present invention is described in detail with reference to the accompanying drawings.

Fig. 1 is that CLEC separates the omeprazole enantiomer chromatogram, and two enantiomorph analysis times, degree of separation was greater than 1.5 in 30 minutes.

Fig. 2 is that CLEC separates the pantoprazole enantiomers chromatogram, and two enantiomorph analysis times, degree of separation was greater than 1.5 in 30 minutes.

Fig. 3 is that CLEC separates Lansoprazole enantiomorph chromatogram, and two enantiomorph analysis times, degree of separation was greater than 1.5 in 70 minutes.

Fig. 4 is that CLEC separates Rabeprazole enantiomorph chromatogram, and two enantiomorph analysis times, degree of separation was greater than 1.5 in 30 minutes.

Embodiment one

1. precision takes by weighing Omeprazole, Pantoprazole, and Lansoprazole and each 12.5mg of Rabeprazole raceme put respectively in the 25ml volumetric flask, are settled to scale with 0.1M NaOH, get the test liquid that each sample concentration is 0.5 mg/mL, 4 ^OCPreserve.

2. at Diamonsil C ₁₈On the chromatographic column, mobile phase is 1 mmol/L L-Histidine, 0.5 mmol/L Schweinfurt green, and pH transfers to 7.0, and ethane nitrile content is 25%, balance 60min, the test liquid 5 μ L of sample introduction 0.5 mg/mL, ultraviolet detects wavelength: 290 nm; The record chromatogram.The separate colors spectrogram is seen Fig. 1-Fig. 4, and Omeprazole, Pantoprazole, Lansoprazole and Rabeprazole enantiomorph obtain degree of separation greater than 1.5 baseline separation.

Claims

1. the chiral isolation analysis method of an anti-ulcer medicament, the method for the four anti-ulcer medicament capillary pipe electrophoresis chiral separation analysis is characterized in that, described method comprises the sample configuration and chromatographic separation condition is set:

A. sample configuration: 0.5 mg/mL sample solution configures with 0.1M NaOH;

B., chromatographic separation condition is set: the separation chromatography post, mobile phase composition, flow velocity, sampling volume detects wavelength.

2. the chiral isolation analysis method of a kind of anti-ulcer medicament according to claim 1 is characterized in that, described chromatographic separation condition comprises: chromatographic column: Dikma Diamonsil C ₁₈, be 150 mm * 4.6 mm I.D., 5 μ m; Mobile phase: 1 mmol/L L-Histidine, 0.5 mmol/L Schweinfurt green, pH 7.0 and 25% acetonitrile, ultrasonic degas behind the membrane filtration of 0.45 μ m then, change mobile phase needs balance 60 min at every turn; Detect wavelength: 290 nm; Flow velocity: 1.0 ml/mL; Sample size: 5 μ L.