Method for separating and detecting daclatasvir hydrochloride and optical isomers thereof

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...

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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

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