Method for quantitatively determining dimer impurities in ticagrelor intermediate TKG
A technology for quantitative determination of ticagrelor, applied in the field of chemical detection, can solve problems such as affecting the quality of ticagrelor products
Pending Publication Date: 2021-02-05
KAIYUAN HENGTAI PHARMA
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Problems solved by technology
[0006] If it is not controlled, it will directly affect the quality of the final product ticagrelor
The impurity is 4 stereoisomer impurities that are not enantiomers of each other, and there is no effective detection method at present
Method used
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[0032] 1. Specificity
[0033] 1. Solution preparation
[0034] Blank solution: water.
[0035] Dimer impurity reference substance stock solution: take an appropriate amount of TKG dimer impurity reference substance, add water to dissolve, and make a solution of about 0.6 mg / ml.
[0036] Test solution: Take an appropriate amount of this product, dissolve it in water to make a solution of about 60 mg / ml.
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The invention discloses a method for quantitatively determining dimer impurities in a ticagrelor intermediate TKG. A cation exchange chromatographic column is adopted, salt-acetonitrile with a high acetonitrile proportion is taken as a mobile phase, four stereoisomer peaks of the dimer impurities can be fused into a symmetrical sharp chromatographic peak, the total content of the dimer impuritiescan be conveniently and accurately determined. The four stereoisomer impurities are all free of chromophore. According to the present invention, a differential refractive index detector is adopted, asatisfactory detection effect can be achieved under the test sample solution concentration and the sample injection volume, and the minimum detection can achieve 0.004% of the test sample solution concentration. Therefore, the content of the dimer impurities in the TKG can be conveniently, accurately and quantitatively determined.
Description
technical field [0001] The invention belongs to the field of chemical detection and relates to a method for quantitatively measuring dimer impurities in ticagrelor intermediate TKG. Background technique [0002] TKG: 2-[[(3aR,4S,6R,6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxolane-4- Base] oxygen group] ethanol, is the important intermediate of anticoagulant ticagrelor, as shown in following formula I: [0003] [0004] During its production process, dimer impurities similar to bimolecular polymerization will be produced, as shown in the following formula II: [0005] [0006] If it is not controlled, it will directly affect the quality of the final product ticagrelor. The impurity is four stereoisomer impurities that are not enantiomers of each other, and there is no effective detection method at present. Contents of the invention [0007] The object of the present invention is to provide a method for quantitatively measuring dimer impurities in TKG...
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IPC IPC(8): G01N30/02G01N30/60G01N30/74
CPCG01N30/02G01N30/60G01N30/74
Inventor 苏贵第董学军荀凤强张硕
Owner KAIYUAN HENGTAI PHARMA



