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High performance liquid chromatographic chiral mobile phase method for separating dakatavir hydrochloride and five optical isomers

A technology of high performance liquid chromatography and optical isomers, which is applied in the field of drug analysis, separation of daclatasvir hydrochloride and its five optical isomers by high performance liquid chromatography chiral mobile phase method, can solve the problem of high cost and applicable sexual inferiority

Inactive Publication Date: 2018-10-12
覃叶枫
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] It can be seen that the method provided by Guo Feng et al. requires the use of expensive chiral columns, which is costly and less applicable than ordinary HPLC methods

Method used

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  • High performance liquid chromatographic chiral mobile phase method for separating dakatavir hydrochloride and five optical isomers
  • High performance liquid chromatographic chiral mobile phase method for separating dakatavir hydrochloride and five optical isomers
  • High performance liquid chromatographic chiral mobile phase method for separating dakatavir hydrochloride and five optical isomers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0113] 1 (aS, bS, cS, dS type), 2 (aR, bS, cS, dS type), 3 (aS, bS, cR, dS type), 4 (aR, bS, cS, dR type), 5 ( aS, bR, cR, dS type) and 6 (aR, bR, cR, dR type) reference substances are self-made or purchased, and the purity is not less than 98%.

[0114] Preparation of mixed reference substance solution: Accurately weigh 10 mg each of 1-6 reference substances, put them in a 20ml measuring bottle, dissolve with acetonitrile and constant volume, and shake well to obtain a mixed control with a concentration of 0.5 mg / ml for 1-6 product solution.

[0115] HPLC chromatographic parameters:

[0116] Chromatograph: Waters 2695 high performance liquid chromatograph;

[0117] Chromatographic column: Agilent ZORBAX Extend-C18 (250×4.6mm, 5μm);

[0118] Mobile phase A phase: acetonitrile aqueous solution with a volume percent concentration of 20%, containing 10 mM L-aspartic acid;

[0119] Mobile phase B phase: acetonitrile aqueous solution with a concentration of 80% by volume, conta...

Embodiment 2

[0127] 1 (aS, bS, cS, dS type), 2 (aR, bS, cS, dS type), 3 (aS, bS, cR, dS type), 4 (aR, bS, cS, dR type), 5 ( aS, bR, cR, dS type) and 6 (aR, bR, cR, dR type) reference substances are self-made or purchased, and the purity is not less than 98%.

[0128] Preparation of mixed reference substance solution: Accurately weigh 10 mg each of 1-6 reference substances, put them in a 20ml measuring bottle, dissolve with acetonitrile and constant volume, and shake well to obtain a mixed control with a concentration of 0.5 mg / ml for 1-6 product solution.

[0129] HPLC chromatographic parameters:

[0130] Chromatograph: Waters 2695 high performance liquid chromatograph;

[0131] Chromatographic column: Agilent ZORBAX Extend-C18 (250×4.6mm, 5μm);

[0132] Mobile phase A phase: acetonitrile aqueous solution with a concentration of 20% by volume, containing 10 mM (2R, 3R)-bis-n-propyl tartaric acid;

[0133] Mobile phase B phase: acetonitrile aqueous solution with a concentration of 80% b...

Embodiment 3

[0141] 1 (aS, bS, cS, dS type), 2 (aR, bS, cS, dS type), 3 (aS, bS, cR, dS type), 4 (aR, bS, cS, dR type), 5 ( aS, bR, cR, dS type) and 6 (aR, bR, cR, dR type) reference substances are self-made or purchased, and the purity is not less than 98%.

[0142] Preparation of mixed reference substance solution: Accurately weigh 10 mg each of 1-6 reference substances, put them in a 20ml measuring bottle, dissolve with acetonitrile and constant volume, and shake well to obtain a mixed control with a concentration of 0.5 mg / ml for 1-6 product solution.

[0143] HPLC chromatographic parameters:

[0144] Chromatograph: Waters 2695 high performance liquid chromatograph;

[0145] Chromatographic column: Agilent ZORBAX Extend-C18 (250×4.6mm, 5μm);

[0146] Mobile phase A phase: acetonitrile aqueous solution with a volume percentage concentration of 20%, containing 10mM D-(+)-di-p-toluyl tartaric acid;

[0147] Mobile phase B phase: acetonitrile aqueous solution with a concentration of 80% ...

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Abstract

The invention discloses a high performance liquid chromatographic chiral mobile phase method for separating dakatavir hydrochloride and five optical isomers. The invention finds out that L-aspartic acid, (2R,3R)-bis-n-propyl tartaric acid, D-(+)-di-p-methylbenzoyl tartaric acid, (1R,2R)-(-)-N-(p-methylphenylsulfonyl)-1,2-diphenylethylenediamine or L-valyl-L-tyrosine as additives are added to a mobile phase, dacatavir hydrochloride and the five optical isomers can be effectively separated by a common C18 liquid chromatographic column, and both of the components reach baseline separation. As those skilled in the art know, a chiral mobile phase method is quite limited and only can separate limited compounds, no systematic theory exists for guiding what kind of compound to be separated by thechiral mobile phase method, and only repeated attempts with a trial-and-error method and undisciplined exploring can be used. Therefore, the method provided by the invention is not obvious to those skilled in the art and is creative as prescribed by patent laws.

Description

technical field [0001] The invention belongs to the field of medicine and relates to drug analysis, in particular to a high-performance liquid chromatography chiral mobile phase method for separating daclatasvir hydrochloride and five optical isomers thereof. Background technique [0002] Daclatasvir dihydrochloride (1), chemical name N,N'-[[1,1'-biphenyl]-4,4'-diylbis[1H-imidazole-5,2-diyl -(2S)-2,1-pyrrolidinediyl[(1S)-1-(1-methylethyl)-2-oxo-1,2-ethanediyl]]]dicarbamic acid dimethyl Ester dihydrochloride is a non-structural protein 5A (NS5A) inhibitor and an anti-hepatitis C virus drug. [0003] 1 (type aS, bS, cS, dS) contains 4 chiral centers. According to literature reports (Chinese patent, CN101778841A, method for synthesizing compounds for the treatment of hepatitis C), 5 chiral isomers will be produced during the preparation of 1, respectively 2(aR,bS,cS,dS type), 3 (type aS, bS, cR, dS), 4 (type aR, bS, cS, dR), 5 (type aS, bR, cR, dS) and 6 (type aR, bR, cR, dR...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/06G01N30/34B01D15/38
CPCG01N30/02B01D15/3833G01N30/06G01N30/34
Inventor 覃叶枫
Owner 覃叶枫
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