Method for separating and detecting daclatasvir hydrochloride and optical isomers thereof

A technology for daclatasvir and isomers, which is applied in the field of separation and determination of daclatasvir hydrochloride and its optical isomers by liquid chromatography, and can solve the problem of poor separation effect, impurity interference peak shape, and inability to adjust the flow phase ratio. Very good improvement and other issues

Active Publication Date: 2018-11-02
SUNSHINE LAKE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The inventors tried to use CHIRALPAK IC, 4.6mm×250mm, 5μm normal-phase chiral chromatography column; CHIRALPAKOD-RH, 4.6mm×250mm, 5μm reverse-phase chiral chromatography column; phenomenonex Lux 5μCellulose-2250×4.6mm reverse-phase chiral chromatography column; Phenomenex Lux 5μCellulose-3250×4.6mm reversed-phase chiral chromatographic column; CHIRALPAKOJ-RH, 4.6mm×150mm, 5μm reversed-phase chiral chromatographic column, etc. are analytical chromatographic columns; the same or different mobile phases are used for analysis a

Method used

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  • Method for separating and detecting daclatasvir hydrochloride and optical isomers thereof
  • Method for separating and detecting daclatasvir hydrochloride and optical isomers thereof
  • Method for separating and detecting daclatasvir hydrochloride and optical isomers thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Detection conditions:

[0054] Instrument: Agilent high performance liquid chromatography, Agilent DAD ultraviolet detector, detection wavelength: 304nm;

[0055] Chromatographic column: Phenomenex Lux 5u Cellulose-1250×4.6mm chiral chromatographic column;

[0056] Diluent: acetonitrile-water (1:1);

[0057] Mobile phase: Potassium hexafluorophosphate and acetonitrile mixed solution, in which potassium hexafluorophosphate is 100mmol / L, pH 2.0 aqueous solution, and the mixing ratio of potassium hexafluorophosphate and acetonitrile is 65:35;

[0058] Flow rate: 1.0mL / min;

[0059] Column temperature: 35°C;

[0060] Injection volume: 5 μL;

[0061] Running time: 70min

[0062] Detection steps:

[0063] Take about 5 mg of the isomer impurity of daclatasvir hydrochloride, weigh it into a 5mL volumetric flask, dissolve it with methanol and dilute to the mark to obtain the isomer impurity stock solution.

[0064] Take about 25mg of daclatasvir hydrochloride sample, accu...

Embodiment 2

[0068] Detection conditions:

[0069] Instrument: Agilent high performance liquid chromatography, Agilent DAD ultraviolet detector, detection wavelength: 304nm;

[0070] Chromatographic column: Phenomenex Lux 5u Cellulose-1250×4.6mm chiral chromatographic column;

[0071] Diluent: acetonitrile-water (1:1);

[0072] Mobile phase: Potassium hexafluorophosphate and acetonitrile mixed solution, in which potassium hexafluorophosphate is 100mmol / L, pH 2.0 aqueous solution, and the mixing ratio of potassium hexafluorophosphate and acetonitrile is 65:35;

[0073] Flow rate: 1.0mL / min;

[0074] Column temperature: 35°C;

[0075] Injection volume: 5 μL;

[0076] Detection steps:

[0077] Take about 25mg of daclatasvir hydrochloride sample, accurately weigh it into a 50mL brown measuring bottle, dissolve it with a diluent and dilute to the mark, shake well, and use it as the test solution.

[0078] Get need testing solution, detect and analyze by above-mentioned condition, record c...

Embodiment 3

[0081] Detection conditions:

[0082] Instrument: Agilent high performance liquid chromatography, Agilent DAD ultraviolet detector, detection wavelength: 304nm;

[0083] Chromatographic column: Phenomenex Lux 5u Cellulose-1 250×4.6mm chiral chromatographic column;

[0084] Diluent: acetonitrile-water (1:1);

[0085] Mobile phase: Potassium hexafluorophosphate and acetonitrile mixed solution, in which potassium hexafluorophosphate is 100mmol / L, pH 2.0 aqueous solution, and the mixing ratio of potassium hexafluorophosphate and acetonitrile is 65:35;

[0086] Flow rate: 1.0mL / min;

[0087] Column temperature: 30°C;

[0088] Injection volume: 5 μL;

[0089] Detection steps:

[0090] Take about 5 mg of the isomer impurity of daclatasvir hydrochloride, weigh it into a 5mL volumetric flask, dissolve it with methanol and dilute to the mark to obtain the isomer impurity stock solution.

[0091] Take about 25mg of daclatasvir hydrochloride sample, accurately weigh it into a 50mL v...

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Abstract

The invention in particular relates to a method for separating and detecting daclatasvir hydrochloride and optical isomers thereof. The method for separating and determining daclatasvir hydrochlorideand optical isomers thereof (impurities) by using liquid chromatography is characterized by comprising the following steps: adopting a chiral chromatographic column taking cellulose tris(3,5-dimethylphenylcarbamate) as a filler, and taking a mixed solution which takes sodium hexafiuorophosphate, potassium hexafluorophosphate, formic acid, acetic acid, phosphoric acid or aqueous phosphate solutionas an aqueous phase and takes acetonitrile or methanol as an organic phase as a mobile phase. According to the separating and detecting method disclosed by the invention, the daclatasvir hydrochlorideand optical isomers thereof (impurities) can be effectively separated, the degree of separation reaches 3.0 or higher, and complete baseline separation is realized, so that the quality of the daclatasvir hydrochloride can be accurately and effectively controlled. With the adoption of the separating method disclosed by the invention, the time of separating and detecting the daclatasvir hydrochloride and optical isomers thereof is within 30-80 minutes. The method disclosed by the invention has the advantages of being simple, rapid, accurate and the like.

Description

technical field [0001] The invention relates to the field of analytical chemistry, in particular to a method for separating and measuring daclatasvir hydrochloride and its optical isomers by liquid chromatography. Background technique [0002] Daclatasvir hydrochloride (Daclatasvir), the chemical name is N,N'-[[1,1'-biphenyl]-4,4'-diylbis[1H-imidazole-5,2-diyl-(2S )-2,1-pyrrolidinediyl[(1S)-1-(1-methylethyl)-2-oxo-2,1-ethanediyl]]]biscarbamic acid C,C'- Dimethyl ester-dihydrochloride, its structure is shown in the following formula (1): [0003] [0004] Daclatasvir hydrochloride is a hepatitis C virus (HCV) NS5A inhibitor, suitable for the treatment of chronic HCV genotype 1 or 3 infection with sofosbuvir. Daclatasvir hydrochloride contains four chiral centers. It is a symmetrical structure with 1 enantiomer and 8 diastereomeric impurities. During the detection of daclatasvir hydrochloride, daclatasvir hydrochloride It is difficult to completely separate and detect Ta...

Claims

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Application Information

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IPC IPC(8): G01N30/06G01N30/74
CPCG01N30/06G01N30/74
Inventor 李亚平尹啟宇张鑫林碧悦杨成刘国柱
Owner SUNSHINE LAKE PHARM CO LTD
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