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Detection method for ezetimibe optical isomers and application thereof

A technology for optical isomers and detection methods, applied in measurement devices, scientific instruments, instruments, etc., can solve the problem of no standard control method, and achieve the effect of high sensitivity, specificity, and simple operation

Active Publication Date: 2016-06-29
TIANJIN INSTITUTE OF PHARMA RESEARCH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Among them, RRR and SSS conformational isomers are included in the import registration standard as related substance inspection objects, but the remaining 5 conformational isomers (as shown below) currently have no standard control methods

Method used

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  • Detection method for ezetimibe optical isomers and application thereof
  • Detection method for ezetimibe optical isomers and application thereof
  • Detection method for ezetimibe optical isomers and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] The choice of solvent and the choice of the concentration of the solution:

[0036] For the choice of solvent for dissolving samples, we used dimethyl sulfoxide, dimethylformamide, ethanol, isopropanol, and acetonitrile to dissolve samples respectively, all of which are easily soluble to samples. Dimethyl sulfoxide and dimethyl formamide produce large solvent peaks on the liquid chromatography column, and are likely to remain in the syringe and column to affect detection. Ethanol or isopropanol should be considered as the preferred choice. Since the n-heptane-ethanol system is selected as the mobile phase, ethanol is finally preferred as the sample solvent.

[0037] We use ethanol as the solvent of the sample, which are respectively formulated as 0.2mg / mL, 0.5mg / mL, 1.0mg / mL, 2mg / mL, 5mg / mL and 10mg / mL. Although they can be separated, the 0.2mg / mL The response is too small, and the concentration of 10mg / mL is too large to be unfavorable for the separation of the sample...

Embodiment 2

[0039] Selection of mobile phase type and flow rate:

[0040] We choose the commonly used normal phase liquid chromatography mobile phase system: n-hexane (A) - isopropanol (B), n-hexane (A) - ethanol (B), n-heptane (A) - isopropanol (B) , n-heptane (A)-ethanol (B), n-hexane (A)-tetrahydrofuran (B), n-heptane (A)-tetrahydrofuran (B); preferred composition: n-heptane (A)-ethanol (B ) screening, the results show that the main peak of the sample in the n-hexane system is wider, and the degree of separation with impurities cannot reach more than 1.5; The heptane-ethanol system is higher than the n-heptane-isopropanol system and the n-heptane-tetrahydrofuran system, so the n-heptane-ethanol system is preferred as the mobile phase system.

[0041]We have investigated the flow rate, and the technical solution can be realized in the range of 0.2-2.0mL / min, but the flow rate of 0.2mL / min is too slow, the peak time of the sample is too long, and the peak shape is too broad; the flow ra...

Embodiment 3

[0043] 1) Instruments and testing conditions

[0044] The E2695 high performance liquid chromatograph produced by U.S. Waters Company, automatic sampler, the ZorbaxNH produced by Agilent Company 2 Chiral analysis column (4.6×250mm, 5μm); mobile phase ratio n-hexane:ethanol (90:10); column temperature: 35°C; flow rate: 1.0mL / min; detection wavelength: 232nm.

[0045] 2) Experimental steps

[0046] We dissolve RRS, SSR, SRR, SRS, and RSR isomers in an appropriate amount with ethanol, add an appropriate amount of ezetimibe to the test sample, and use mobile phase to prepare 1 mg of ezetimibe per ml, containing RRS, SSR, A solution of 1 μg of SRR, SRS, and RSR isomers was used as the system suitability 1 solution. Inject 20 μL, record the chromatogram, see the results figure 1 .

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Abstract

The invention provides a liquid chromatography detection method for ezetimibe optical isomers; the detection method comprises the following chromatographic conditions: chromatographic columns comprise a silica gel column, an amino column, a cyano column and a chiral column; mobile phases comprise n-hexane (A)-isopropanol (B), n-hexane (A)-ethanol (B), n-heptane (A)-isopropanol (B), n-heptane (A)-ethanol (B), n-hexane (A)-tetrahydrofuran (B), or n-heptane (A)-tetrahydrofuran (B); the ratio of the mobile phases is (A:B)=95:5-50:50; the mobile phase flow rate is 0.2-2.0 mL / min; the detection wavelength is 200-400 nm; the column temperature is 25-40 DEG C; the sample injection volume is 1-40 [mu]L; a detector is an ultraviolet detector or a diode array detector. The detection method provided by the invention has the advantages of relatively high sensitivity and specificity, and concise operation, has the separation degree conforming to standards, can rapidly and accurately detect five kinds of optical isomers of ezetimibe, and has quite important significance on quality control of the cholesterol absorption inhibitor ezetimibe.

Description

technical field [0001] The invention belongs to the technical field of drug analysis, and in particular relates to a method for detecting ezetimibe optical isomers and an application thereof. Background technique [0002] Ezetimibe (English name: Ezetimibe), the molecular formula is C 24 h 21 f 2 NO 3 , molecular weight 409.43, CAS accession number: 163222-33-1. The pure product of ezetimibe is a white solid with a melting point of 162.0-167.0°C. Its structural formula is as shown in formula I: [0003] [0004] Ezetimibe is a new class of cholesterol-lowering drugs for the treatment of primary hypercholesterolemia. Compared with statins, which inhibit the synthesis of cholesterol in the liver, ezetimibe works by selectively inhibiting the absorption of cholesterol in the intestine. In addition, the combination of ezetimibe and statins can achieve a more superior effect of lowering low-density lipoprotein cholesterol. At present, domestic clinical application of e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
Inventor 郝英魁蒋庆峰吴学丹金松子罗振福尹文龙
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH
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