Method for using liquid chromatography to separate and measure apremilast and enantiomer thereof

A technology of enantiomers and liquid chromatography, which is applied in the field of separation and determination of apremilast and its enantiomers by liquid chromatography, can solve the problem of effective separation of apremilast and its corresponding isomers, peak Shape difference, low column efficiency and other problems, to achieve the effect of quality controllable, good peak shape, high column efficiency

Active Publication Date: 2015-08-05
CHONGQING PHARMA RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] It is difficult to effectively separate Apremilast from its corresponding isomers by HPLC with conventional general chiral columns and conventional mobile phases, the peak shape is very poor, and the column efficiency is very low

Method used

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  • Method for using liquid chromatography to separate and measure apremilast and enantiomer thereof
  • Method for using liquid chromatography to separate and measure apremilast and enantiomer thereof
  • Method for using liquid chromatography to separate and measure apremilast and enantiomer thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Instruments and Conditions

[0037] American Agilent 1100 liquid chromatograph and Instrument workstation; automatic sample injection; instrument: CHIRALPAK AS-H (5μm, 250×4.6mm) as the separation column; n-hexane-methanol-isopropanol (volume ratio 100: 900:100) mobile phase; detection wavelength: 230nm; flow rate: 1.0ml / min; injection volume: 10μl; column temperature: 35°C.

[0038] Experimental steps:

[0039] Weigh 100.57 mg of Apremilast working reference substance and 100.79 mg of enantiomer reference substance, put them in 10ml measuring bottles respectively, dissolve them with acetonitrile and dilute to the mark, shake well, accurately measure 0.5ml, put them in 100ml measuring bottles respectively , dilute to the mark with the mobile phase, shake up, as the stock solution of Apremilast and the stock solution of the enantiomer, accurately measure 1.0ml respectively and put it in a 10ml measuring bottle, dilute to the mark with the mobile phase, shake up to get t...

Embodiment 2

[0046] Determination of apremilast enantiomers by liquid chromatography.

[0047] Take about 10 mg of this product, weigh it accurately, put it in a 10 ml measuring bottle, add 2 ml of acetonitrile to dissolve, dilute to the mark with mobile phase, shake well, and use it as the test solution. Precisely measure 0.5ml, put it in a 100ml measuring bottle, dilute to the mark with mobile phase, shake well, and use it as the reference substance solution. Carry out liquid chromatography analysis according to the chromatographic condition of embodiment 1, need testing solution except solvent peak and system peak, if there is enantiomer at about 0.54 place of apremilast relative retention time, calculate according to self-control method Its content, if there is no chromatographic peak at the relative retention time of about 0.54, there is no need to calculate the content. see results Figure 5 , Figure 6 .

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Abstract

The invention relates to a method for using a liquid chromatography to separate and measure apremilast and enantiomer thereof. The method includes that using spherical silica gel coated with chiral polymer at surface as a chiral chromatographic column, using alkane-different concentrations of polarity organic solvent as mobile phase, wherein the polarity organic solvent is composed of first organic solvent and second organic solvent, the alkane is selected from normal hexane, normal heptane, cyclohexane and methylene dichloride, the first organic solvent is isopropanol, and the second organic solvent is selected from methanol, ethanol and acetonitrile. The method for using the liquid chromatography to separate and measure the apremilast and enantiomer thereof solves the problem that the apremilast and enantiomer thereof are difficult to separate for the separation and measurement, and accordingly the controllable quality of the apremilast and the preparation thereof is guaranteed.

Description

technical field [0001] The invention belongs to the field of analytical chemistry, and in particular relates to a method for separating and measuring apremilast and its enantiomers by liquid chromatography. Background technique [0002] Apremilast is an inhibitor of phosphodiesterase-4 (PDE-4), developed by the U.S. celgene company, and its molecular formula is C 22 h 24 N 2 o 7 S, the chemical structural formula is shown in the following formula (I) compound, its chemical name is: N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methyl sulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl}acetamide. During the synthesis of apremilil, the enantiomer of apremilil ((R)-N-{2-[1-(3-ethoxy-4-methoxyphenyl)- 2-(Methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}acetamide, the chemical structure of which is shown in the compound of formula (II) below. [0003] [0004] It is difficult to effectively separate apremilast and its corresponding isomers by using conventional general chi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
Inventor 代广会陈志锋张道林
Owner CHONGQING PHARMA RES INST
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