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A kind of method for separating and detecting daclatasvir hydrochloride and its optical isomers

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

Active Publication Date: 2022-07-08
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 and detection of the test samples, and the results show The above-mentioned chromatographic columns have poor separation effects on daclatasvir hydrochloride and its isomers in the test product, or there may be interference from impurities or poor peak shapes, and the adjustment of the mobile phase ratio can not be well improved; while the phenomenonex Lux 5μCellulose -1 (the stationary phase is cellulose tris(3,5-dimethylphenylcarbamate)) 250×4.6mm, the separation effect of 5μm reversed-phase chiral chromatography column is better

Method used

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  • A kind of method for separating and detecting daclatasvir hydrochloride and its optical isomers
  • A kind of method for separating and detecting daclatasvir hydrochloride and its optical isomers
  • A kind of method for separating and detecting daclatasvir hydrochloride and its optical isomers

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Detection conditions:

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

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

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

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

[0058] Flow rate: 1.0mL / min;

[0059] Column temperature: 35℃;

[0060] Injection volume: 5μL;

[0061] Running time: 70min

[0062] Detection steps:

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

[0064] Take about 25 mg of daclatasvir hydrochloride sample, accurately weigh it into a 50 mL volumetric flask, a...

Embodiment 2

[0068] Detection conditions:

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

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

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

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

[0073] Flow rate: 1.0mL / min;

[0074] Column temperature: 35℃;

[0075] Injection volume: 5μL;

[0076] Detection steps:

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

[0078] Take the test solution, carry out detection and analysis according to the above conditions, record the chromatogram, see the resul...

Embodiment 3

[0081] Detection conditions:

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

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

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

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

[0086] Flow rate: 1.0mL / min;

[0087] Column temperature: 30℃;

[0088] Injection volume: 5μL;

[0089] Detection steps:

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

[0091] Take about 25 mg of daclatasvir hydrochloride sample, accurately weigh it into a 50 mL volumetric flask, add 1 mL of isomer impurity st...

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Abstract

The invention specifically relates to a method for separating and detecting daclatasvir hydrochloride and its optical isomers. A method for separating and measuring daclatasvir hydrochloride and its optical isomers (impurities) by liquid chromatography, characterized in that, using cellulose tris(3,5-dimethylphenylcarbamate) It is a chiral chromatographic column with fillers, and the mobile phase is a mixed solution of sodium hexafluorophosphate, potassium hexafluorophosphate, formic acid, acetic acid, phosphoric acid or phosphate aqueous solution and an organic phase of acetonitrile or methanol. The separation and detection method of the present invention can effectively separate daclatasvir hydrochloride and its optical isomers (impurities), the separation degree reaches more than 3.0, and complete baseline separation, so that the quality of daclatasvir hydrochloride can be accurately and effectively controlled. By adopting the separation method of the present invention, the time for separating and detecting daclatasvir hydrochloride and its optical isomers is within 30-80 minutes, and the method of the present invention has the advantages of simplicity, rapidity, accuracy and the like.

Description

technical field [0001] The invention relates to the field of analytical chemistry, in particular to a method for separating and determining daclatasvir hydrochloride and its optical isomers by liquid chromatography. Background technique [0002] Daclatasvir hydrochloride (Daclatasvir), 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 indicated for the treatment of chronic HCV genotype 1 or 3 infection with sofosbuvir. Daclatasvir hydrochloride contains four chiral centers, and itself is a symmetrical structure, with 1 enantiomer and 8 diastereomer impurities. In the process of detecting daclatasvir hydrochloride, daclatasvir hydrochloride It is difficult to completely separate and ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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