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Separation detection method of pregabalin chiral isomers

A chiral isomer, pregabalin technology, applied in the field of analytical chemistry, can solve the problems of small sample volume, weak UV absorption, troublesome post-processing, etc., and achieve mild reaction conditions, high analytical sensitivity, and strong UV absorption. Effect

Active Publication Date: 2015-07-15
北京紫萌医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But pregabalin is terminal absorption, and ultraviolet absorption is not strong, and in the prior art: Chinese invention patent (patent number: 200510057381.8, a kind of separation and determination method of pregabalin chiral isomers), Indian Pharmacopoeia 2010 edition No. 1960 N α -(5-Fluoro-2,4-dinitrophenyl)-L-amino acid compounds are derivatized as derivatization reagents, and then enter the liquid chromatography system for analysis after post-treatment. The derivatization in these documents Both methods need to first dissolve pregabalin with hydrochloric acid, then neutralize it with sodium hydroxide, and derivatize it with the derivatization reagent solution under heating conditions, and decompress in the system of phosphorus pentoxide and potassium hydroxide after the reaction is completed. Dry to remove the organic solvent with low boiling point, then dissolve and filter with other solvents to prepare the test solution, the post-processing is very troublesome, and a lot of inevitable errors are brought to the quantitative operation, although the patent No. is 200910045925.7 (pregabalin and The separation and detection method of its chiral isomers) adopts microwave derivatization method: take 20 μl of sample solution, 200 μl of derivatization reagent solution and 20 μl of 0.05mol / L triethylamine solution, heat derivatization with 600W microwave for 3min, then cool to room temperature and add 0.05mol / L acetic acid solution 20 μ l, as the test solution, although this method avoids the cumbersome steps of follow-up treatment, it needs to prepare sample solution, derivatization solution, triethylamine solution and acetic acid solution, and the sample volume is small, still More troublesome and prone to errors

Method used

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  • Separation detection method of pregabalin chiral isomers
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  • Separation detection method of pregabalin chiral isomers

Examples

Experimental program
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Effect test

Embodiment 1

[0024] (1) Instruments and conditions

[0025] Mobile phase: n-hexane-absolute ethanol=85:15

[0026] Detection wavelength: 208nm

[0027] Column: AD-H 250×4.5mm, 5μm

[0028] Flow rate: 1.0ml / min

[0029] Column temperature: 35°C

[0030] Injection volume: 20ul

[0031] (2) Experimental steps

[0032] Take 25 mg of pregabalin mixture, add 50 mg of fluorenylmethoxycarbonyl chloride, put it in a 50 ml volumetric flask, add absolute ethanol for ultrasonic dissolution, then dilute to the mark with absolute ethanol and shake well, as a system suitability solution.

[0033] Take the system suitability solution and analyze it under the above conditions. see results figure 1 , where the retention time is 8.393min for pregabalin, where the retention time is 9.835min for pregabalin isomers, and the remaining peaks are peaks of unreacted derivative reagents, and the separation between the two is 2.352.

Embodiment 2

[0035] (1) Instruments and conditions

[0036] Mobile phase: n-hexane-absolute ethanol=95:5

[0037] Detection wavelength: 205nm

[0038] Column: AD-H 250×4.5mm, 5μm

[0039] Flow rate: 1.0ml / min

[0040] Column temperature: 25°C

[0041] Injection volume: 20ul

[0042] (2) Experimental steps

[0043] Take 25mg of pregabalin mixture, add 75mg of fluorenylmethoxycarbonyl chloride, put it in a 50ml volumetric flask, add 20ml of absolute ethanol for ultrasonic dissolution, then dilute to the mark with n-hexane and shake well as a system suitability solution.

[0044] Take the system suitability solution and analyze it under the above conditions. see results figure 2 , where the retention time is 23.027min is pregabalin, where the retention time is 28.313min is pregabalin isomers, and the remaining peaks are peaks of unreacted derivative reagents, and the resolution is 3.32.

Embodiment 3

[0046] (1) Instruments and conditions

[0047] Mobile phase: n-hexane-dehydrated ethanol-dehydrated methanol=90:5:5

[0048] Detection wavelength: 210nm

[0049] Column: AD-H 250×4.5mm, 5μm

[0050] Flow rate: 0.8ml / min

[0051] Column temperature: 25°C

[0052] Injection volume: 20ul

[0053] (2) Experimental steps

[0054] Take 25mg of pregabalin mixture, add 100mg of fluorenylmethoxycarbonyl chloride, put it in a 50ml volumetric flask, add 20ml of absolute ethanol for ultrasonic dissolution, then dilute to the mark with n-hexane and shake well, as a system suitability solution.

[0055] Take the system suitability solution and analyze it under the above conditions. see results image 3 , where the retention time is 21.426min is pregabalin, where the retention time is 25.807min is pregabalin isomers, and the remaining peaks are the peaks of unreacted derivative reagents, and the resolution is 3.09.

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Abstract

The invention provides a derivatizing separation detection method of pregabalin chiral isomers and belongs to the field of analytical chemistry. According to the method, pre-column derivatization is performed on pregabalin by taking fluorenylmethoxycarbonyl chloride as a derivatization reagent; a CHIRALPAK. AD-H chiral chromatographic column is taken as a chromatographic column, and the mixture of n-hexane and absolute ethyl alcohol is taken as a moving phase, and separation detection can be realized by use of efficient liquid chromatography. The precolumn derivatization method has the advantages of mild reaction conditions, stable derivation products, high reaction speed, few side reactions, no interference of excessive derivatization reagent on the measurement, realization of separation of the pregabalin and the pregabalin chiral isomers, and the like.

Description

technical field [0001] The invention relates to a method for separating and detecting chiral isomers of pregabalin, which belongs to the field of analytical chemistry. technical background [0002] Pregabalin, chemically known as (S)-3-(aminomethyl)-5-methylhexanoic acid, is used to treat epilepsy and nerve pain. The chiral isomer of pregabalin has almost no pharmacological activity, and its chemical name is (R)-3-(aminomethyl)-5-methylhexanoic acid, which is an important impurity of pregabalin and is also used to control the quality of pregabalin important indicators. But pregabalin is terminal absorption, and ultraviolet absorption is not strong, and in the prior art: Chinese invention patent (patent number: 200510057381.8, a kind of separation and determination method of pregabalin chiral isomers), Indian Pharmacopoeia 2010 edition No. 1960 N α -(5-Fluoro-2,4-dinitrophenyl)-L-amino acid compounds are derivatized as derivatization reagents, and then enter the liquid chr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/88G01N30/06
Inventor 尚宝虎王雪
Owner 北京紫萌医药科技有限公司
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