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Detection method for diastereoisomer for splitting glycopyrronium bromide intermediate

A technology for diastereomers and glycopyrronium bromide is applied in the field of detection of diastereomers, which can solve problems such as large differences in structure and polarity, inappropriate separation and the like, and achieve good guiding significance and methods. Exclusive and durable, high-sensitivity effects

Active Publication Date: 2022-05-03
山东泰合医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In the investigation and comparison of glycopyrronium bromide analysis methods, it was found that the isomer analysis methods of glycopyrronium bromide raw materials were reported more, but due to the difference between glycopyrronium bromide intermediate (GP-5NA) and glycopyrronium bromide raw materials The structure and polarity are quite different, so it is not suitable for the separation of isomers in intermediates

Method used

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  • Detection method for diastereoisomer for splitting glycopyrronium bromide intermediate
  • Detection method for diastereoisomer for splitting glycopyrronium bromide intermediate
  • Detection method for diastereoisomer for splitting glycopyrronium bromide intermediate

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Embodiment 1

[0043] Embodiment 1, a kind of detection method of the diastereoisomer of resolution glycopyrronium bromide intermediate

[0044] Test equipment: Waters high-performance liquid chromatography, the model is Acquity Arc. The detector adopts 2489 ultraviolet detector.

[0045] Chromatographic conditions: use amylose-tris(3-chloro-5-methylphenylcarbamate) bonded silica gel as filler (Daicel IG-3, 4.6mm×250mm, 3μm); use 0.02mol / L ammonium bicarbonate solution-acetonitrile (45:55) is the mobile phase; the flow rate is 0.6 ml per minute; the column temperature is 15° C.; the detection wavelength is 219 nm; the injection volume is 10 μl.

[0046] Sample preparation: Test solution: Take about 25mg of this product, weigh it accurately, put it in a 25ml measuring bottle, add water-acetonitrile (45:55) to dissolve and dilute to the mark, and shake well.

[0047] Determination method: Accurately measure the solution of the test product, inject it into the liquid chromatograph, and recor...

Embodiment 2

[0048] Embodiment 2, verification test

[0049] 2.1, specificity test

[0050] Blank solvent: water-acetonitrile (45:55);

[0051]Reference substance stock solution: take appropriate amount of 3S-2S-GP-5NA reference substance, 3R-2R-GP-5NA reference substance, 3S-2R-GP-5NA reference substance and 3R-2S-GP-5NA reference substance, and accurately weigh , were placed in different measuring bottles, dissolved in water-acetonitrile (45:55) and quantitatively diluted to make a solution containing about 0.75 mg / ml per 1 ml.

[0052] Isomer monomer localization solution: take appropriate amount of 3S-2S-GP-5NA reference substance, 3R-2R-GP-5NA reference substance, 3S-2R-GP-5NA reference substance and 3R-2S-GP-5NA reference substance , Accurately weighed, put in different measuring bottles, add water-acetonitrile (45:55) to dissolve and quantitatively dilute to make a solution containing about 0.03mg / ml in 1ml.

[0053] Mixed solution of 4 isomers: take appropriate amount of 3S-2S-G...

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Abstract

The invention discloses a method for detecting diastereoisomers for resolving glycopyrronium bromide intermediates, which comprises the following steps: adopting a high performance liquid chromatography, using an IG-3 chiral chromatographic column provided by a Daexid Drug Chiral Technology Co., Ltd., and using an ammonium bicarbonate solution (0.01 mol / L-0. 10 mol / L)-acetonitrile as a mobile phase, wherein the used acetonitrile is required to be at an HPLC level; and the flow velocity of the mobile phase is 0.5-0.7 ml per minute. The invention provides a detection method for separating four isomers in a glycopyrronium bromide intermediate by high performance liquid chromatography, which is used for detecting diastereoisomer impurities of the glycopyrronium bromide intermediate and calculating the content of the diastereoisomer impurities by using a peak area normalization method. The method has the characteristics of simplicity in operation, high sensitivity, high accuracy and the like.

Description

technical field [0001] The invention relates to the technical field of drug analysis, in particular to a method for detecting diastereoisomers of a glycopyrronium bromide intermediate. Background technique [0002] Glycopyrrolate is a quaternary ammonium anticholinergic drug indicated for the treatment of adults with chronic obstructive pulmonary disease (COPD), including chronic bronchitis or emphysema, for maintenance bronchodilation to relieve symptoms. The structural formula of glycopyrronium bromide is shown in formula I. [0003] [0004] Similarly, its intermediate also contains two chiral carbon atoms, and there are two pairs of enantiomers (RS, SR, RR, SS), that is, 4 chiral isomers, the structure of the glycopyrronium bromide intermediate As shown in Formula II: [0005] [0006] Chiral drugs refer to the existence of chiral centers in the molecular structure of drugs; drugs composed of chiral compounds with pharmacological activity, which contain only effe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/06G01N30/30G01N30/32G01N30/34G01N30/74G01N30/86
CPCG01N30/02G01N30/06G01N30/30G01N30/32G01N30/34G01N30/74G01N30/8675G01N2030/324
Inventor 刘飞飞姜明明王苗苗孙孝丽孙迎基李铁军
Owner 山东泰合医药科技有限公司