A method for the separation and determination of ezetimibe and related substances by high performance liquid chromatography

Abstract

The invention belongs to field of analytical chemistry, and specifically relates to a method for separating and measuring ezetimibe and relevant substances through high performance liquid chromatography. According to the method, during an analysis process of high performance liquid chromatography, an adopted chromatographic column takes phenylsilane bonded silicone as a filler, and takes a solution A and an organic solution B as a moving phase, wherein the solution A and the organic solution B are according to a certain ratio, for elution. The solution A is an aqueous acid, or a mixed solution of acetonitrile and methanol. The method is suitable for six relevant substances of ezetimibe and is used for separating and measuring one or several relevant substances at the same time. In comparison with the prior art, the efficiency of separation and detection is improved. By using the method, alkaline degradation impurities of ezetimibe are detected, and the six relevant substances are accurately effectively separated from other degradation impurities. A raw material of ezetimibe is accurately guaranteed; the quality of a preparation of ezetimibe is controllable; and safety and effectiveness of the final product is ensured.

Description

technical field [0001] The invention belongs to the field of analytical chemistry, and in particular relates to a method for separating and measuring ezetimibe and related substances by using high-performance liquid chromatography. Background technique [0002] Ezetimibe is a cholesterol-lowering drug that can be used alone or in combination with HMG-CoA reductase inhibitors (statins) in the treatment of primary (heterozygous familial or non-familial) hypercholesterolemia to reduce total cholesterol , low-density lipoprotein cholesterol, apolipoprotein, non-high-density lipoprotein cholesterol; it can also be used for the treatment of homozygous familial hypercholesterolemia. Molecular formula is C 24 h 21 f 2 NO 3 , the chemical name is 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxybenzene Base)-2-azetidin (azetidin) ketone, its chemical structural formula is as follows: [0003] [0004] In the synthesis process of ezetimibe, some ...

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Problems solved by technology

[0007] At present, there are import registration standards (JX20070201) for the analysis and detection methods of related substances in ezetimibe. Octadecylsilane-bonded silica gel is used as filler, and 0.05mol / L potassium dihydrogen phosphate solution: acetonitrile: tetrahydrofuran (65: 25:10) is the mobile phase for isocratic elution, the flow rate is 1.0ml / min, the detection wavelength is 232nm, the column temperature is 25°C, the injection volume is 30μl, and the detection time is twice the retention time of the main peak. However, this The above-mentioned related substance 3 and related substance 4 cannot be detected by the standard method; in the alkali degradation test, the related substance 6 and other degradation impurities cannot be separated

[0008] In addition, the invention patent with application number 201210337025.1 discloses a method for separating and determining ezetimibe-related substances by liquid chromatography. The acidic aqueous solution-organic phase is the mobile phase, and the content of ezetimibe and its related substances is quantitatively determined. The acid in the acidic aqueous solution is one of phosphoric acid, carbonic acid, formic acid, and acetic acid, and the organic phase is methanol, acetonitrile, propanol, One of isopropanol; the invention patent with application number 201410015689.5 discloses a method for separating and determining the chemical purity of related substances in ezetimibe intermediates by liquid chromatography. The method uses octadecylsilane to bond silica gel The chromatographic column is a packing, with a certain proportion of phosphoric acid aqueous solution-organic phase as the mobile phase, quantitative determination of the content of ezetimibe intermediates and related substances, the organic phase is one of methanol, acetonitrile, propanol, and isopropanol But similarly, neither the method disclosed in the invention patent with application number 201210337025.1 nor the method disclosed in the invention patent with application number 201410015689.5 can completely separate and detect the above-mentioned impurities, indicating that the methods disclosed in the current prior art cannot be applied at the same time For the detection of the above 6 impurities

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