Unlock instant, AI-driven research and patent intelligence for your innovation.

A method for separating and purifying impurities in semi-synthetic docetaxel

A docetaxel, separation and purification technology, applied in the field of separation and purification of impurities A and E in semi-synthetic docetaxel, can solve the problems of high market price and difficulty in obtaining, and achieve the effect of simple operation

Active Publication Date: 2019-04-23
无锡紫杉药业股份有限公司
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

EP and USP clearly stipulate that the limit of the related substance impurity A in the finished product is 0.2%. Controlling the content of impurity A in the finished product has also become the focus of many medical workers. In addition, the polarity of impurity A and the finished product is extremely Similar, it is difficult to obtain, so the market price is expensive, which is also the difficulty of studying impurity A in semi-synthetic docetaxel

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A method for separating and purifying impurities in semi-synthetic docetaxel
  • A method for separating and purifying impurities in semi-synthetic docetaxel
  • A method for separating and purifying impurities in semi-synthetic docetaxel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Weigh 10 g of the semi-synthetic docetaxel sample, add 500 ml of methanol to completely dissolve it, add it to 10 g of MCI packing, and let it dry naturally to obtain the MCI packing of the adsorbed sample, put it on a 100 g MCI column for separation, and use 20%, 30%, and 40%, 50%, 60% and 70% ethanol elution, collect 40% and 50% elution eluate, evaporate to dryness under reduced pressure to obtain about 50 mg of mixed off-white powder containing impurities A and E, add 50 ml of Water ethanol makes the white powder that obtains dissolve completely, joins in 50mg silica gel (100-200 mesh) packing, obtains the silica gel packing of adsorption sample, and the silica gel (300-400 mesh) column of upper 500mg is separated, and with normal hexane and acetone Mixed solvents were used for gradient (5:1, 3.5:1, 3:1, 2.5:1 and 2:1) elution, the filtrate was subjected to thin-layer analysis, and the fractions with consistent thin-layer behavior were combined, and the two obtained ...

Embodiment 2

[0041] Weigh 10g of semi-synthetic docetaxel sample, add 100ml of acetone to dissolve completely, add it to 50g of MCI filler, and let it air-dry naturally to obtain the MCI filler of adsorption sample, put it on a 2500g MCI column for separation, and use 20%, 30%, 40%, 50%, 60% and 70% ethanol elution, collect 40% and 50% elution eluate, evaporate to dryness under reduced pressure to obtain about 50 mg of mixed off-white powder containing impurities A and E, add 500 ml of Dehydrated alcohol completely dissolves the white powder, air-dries it naturally, adds it to 500 mg of silica gel (100-200 mesh) packing, obtains the silica gel packing of the adsorption sample, and separates it on a 3 g silica gel (300-400 mesh) column. Mixed solvents of acetone (5:1, 3.5:1, 3:1, 2.5:1 and 2:1) were used for gradient elution, and the filtrate was subjected to thin-layer analysis, and the fractions with consistent thin-layer behavior were combined, and the obtained The two impurities were dr...

Embodiment 3

[0043]Weigh 10g of the semi-synthetic docetaxel sample, add 250ml of absolute ethanol to dissolve completely, add it to 30g of MCI filler, and let it air-dry naturally to obtain the MCI filler of the adsorbed sample, put it on a 600g MCI column for separation, and use 20%, 30 %, 40%, 50%, 60% and 70% ethanol for elution, collect 40% and 50% eluents, and evaporate to dryness under reduced pressure to obtain about 50 mg of a mixed off-white powder containing impurities A and E. Add 50ml of dehydrated ethanol to completely dissolve the white powder, air-dry naturally, add to 150mg of silica gel (100-200 mesh) packing, obtain the silica gel packing of the adsorption sample, put on 3g of silica gel (300-400 mesh) column to separate, use A mixed solvent of n-hexane and acetone (5:1, 3.5:1, 3:1, 2.5:1 and 2:1) was used for gradient elution, and the filtrate was subjected to TLC analysis, and the fractions with consistent TLC behavior were combined, The obtained two impurities were dr...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a separating and purifying method for impurities in semi-synthesized docetaxel. The method comprises the following steps: dissolving a sample of semi-synthesized docetaxel, adding MCI into a solution obtained after dissolving and removing a solvent via air drying so as to obtain a MCI filling material having adsorbed the sample; loading the MCI filling material having adsorbed the sample into a MCI column, carrying out elution so as to obtain a mixture of an impurity A and an impurity E in standard semi-synthesized docetaxel EP; dissolving the mixture with an organic solvent and adding a solution obtained after dissolving into silica gel to allow a sample to be adsorbed so as to silica gel having adsorbed the sample; adding the silica gel having adsorbed the sample into a silica gel column and carrying out gradient elution by using an organic solvent; and carrying out concentration and drying so as to obtain high-purity impurity A monomer and impurity E monomer respectively. The separating and purifying method provided by the invention prepares the high-purity compounds by using a combination of MCI column chromatography and silica gel column chromatography on the basis of the structural characteristics of the impurity A and the impurity E in semi-synthesized docetaxel; and the method is simple to operate and highly efficient.

Description

technical field [0001] The invention relates to a method for separating and purifying compounds, in particular to a method for separating and purifying impurities A and E in semi-synthetic docetaxel. Background technique [0002] MCI is a reverse resin packing made of styrene polymer, which is suitable for separating moderately hydrophobic compounds. Due to its benzene ring structure, it has different separation selectivity compared with other types of reversed-phase packings, especially for compounds with benzene rings or differences in the number of benzene rings. The eluent for this packing generally elutes gradiently from a high proportion of the aqueous phase to a high proportion of the organic phase. [0003] The separation principle of silica gel chromatography is to separate compounds according to their different adsorption forces on silica gel. The separation process of silica gel column chromatography is a process of adsorption-desorption-re-adsorption-re-desorpt...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D305/14
CPCC07D305/14
Inventor 李秋月袁谱龙汤伟彬王莉佳王旭阳
Owner 无锡紫杉药业股份有限公司