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Method for detecting related substances of ambroxol hydrochloride raw material and injection

A technology of ambroxol hydrochloride and a detection method, applied in the field of drug analysis, can solve the problems of inability to detect multiple impurities at the same time, cumbersome gradient elution procedures, and high requirements for instrument configuration, and achieve a stable detection method, high sensitivity and simple method. Effect

Active Publication Date: 2021-06-29
CSPC OUYI PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method is mainly used to detect impurity B and impurity E in ambroxol hydrochloride injection, and cannot simultaneously detect five kinds of impurities (impurity A, impurity B, impurity C, impurity D, impurity E)
[0007] Chinese patent CN106950291A discloses a kind of detection method of ambroxol hydrochloride injection related substance, this method can detect five kinds of impurities in the ambroxol hydrochloride injection, this method adopts gradient elution, needs simultaneously in mobile phase (PH value=4.0 ) with succinic acid, the gradient elution procedure is cumbersome, the requirements for instrument configuration are also high, and the method setting is complicated. Therefore, this technique is not suitable for industrial production
Most of the current detection methods for ambroxol hydrochloride raw materials and related substances in its preparations only detect one or two impurities, and gradient elution is used, which cannot detect multiple impurities at the same time

Method used

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  • Method for detecting related substances of ambroxol hydrochloride raw material and injection
  • Method for detecting related substances of ambroxol hydrochloride raw material and injection
  • Method for detecting related substances of ambroxol hydrochloride raw material and injection

Examples

Experimental program
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Effect test

Embodiment 1

[0126] Example 1: Synthesis and structure confirmation of impurity F

[0127] In the reaction kettle, add 23.9g (0.086eq) of 2-amino-3,5-dibromobenzaldehyde, 10g (0.066eq) of cis-4-aminocyclohexanol hydrochloride, and 350ml of methanol; stir the reaction at 52°C 9h, the crude product was obtained, and the crude product was recrystallized from acetone to obtain 18.5 g of the final product cis-4-[[(2-amino-3,5-dibromophenyl)methylene]amino]cyclohexanol, with a molar yield of 74.6 %. 99.73% pure. NMR spectra, mass spectra, chromatograms such as figure 1 , figure 2 , image 3 shown.

Embodiment 2

[0128] Embodiment 2: the synthesis of impurity F

[0129] In the reaction kettle, add 22.1g (0.079eq) of 2-amino-3,5-dibromobenzaldehyde, 10g (0.066eq) of cis-4-aminocyclohexanol hydrochloride, and 220ml of methanol; stir the reaction at 55°C 8h, the crude product was obtained, and the crude product was recrystallized from acetone to obtain 18.1 g of the final product cis-4-[[(2-amino-3,5-dibromophenyl)methylene]amino]cyclohexanol, with a molar yield of 72.8 %. 99.68% pure.

Embodiment 3

[0130] Embodiment 3: the synthesis of impurity F

[0131] In the reaction kettle, add 25.8g (0.092eq) of 2-amino-3,5-dibromobenzaldehyde, 10g (0.066eq) of cis-4-aminocyclohexanol hydrochloride, and 510ml of methanol; stir the reaction at 50°C 10h, the crude product was obtained, and the crude product was recrystallized from acetone to obtain 16.7 g of the final product cis-4-[[(2-amino-3,5-dibromophenyl)methylene]amino]cyclohexanol, with a molar yield of 67.4 %. 99.71% pure.

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Abstract

The invention provides a novel impurity cis-4-[[(2-amino-3, 5-dibromophenyl)methylene]amino]cyclohexanol(impurity F) existing in an ambroxol bulk drug and a preparation. The invention further provides a preparation method of the impurity. The invention further provides a detection method capable of simultaneously detecting six impurities such as an impurity A, an impurity B, an impurity C, an impurity D, an impurity E and an impurity F in the ambroxol raw material medicine and the ambroxol injection. The method is simple, convenient, high in sensitivity and stable; and the separation degree of each impurity can reach 2.0 or above, the six impurities generated in the preparation, production and storage processes of the ambroxol bulk drug and the injection can be effectively detected, and the quality of the ambroxol bulk drug and the injection can be effectively reflected.

Description

technical field [0001] The invention belongs to the technical field of drug analysis, and in particular relates to a method for detecting ambroxol hydrochloride raw materials and related substances in injections. Background technique [0002] Ambroxol hydrochloride is a new generation of respiratory mucus regulator with superior expectorant effect. Compared with the first-generation and second-generation expectorant drugs, ambroxol hydrochloride has a strong mucolytic effect, and its biggest feature is that it can stimulate alveolar type II cells and promote the synthesis and secretion of alveolar surfactant, thereby It effectively enhances mucus transport and promotes expectoration. It is currently the most effective expectorant in clinical practice. The combination of ambroxol and antibiotics can increase the ratio of antibiotic lung tissue / plasma concentration, shorten the time of antibiotic treatment and have mild adverse reactions. [0003] [0004] The European Pha...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/74G01N30/34G01N30/06G01N30/04G01N30/86C07C251/24C07C249/02
CPCG01N30/02G01N30/74G01N30/34G01N30/06G01N30/04G01N30/8634G01N30/8679C07C251/24G01N2030/047C07C2601/14Y02A50/30
Inventor 田小月焦魁良袁晓旭刘楠楠李雯
Owner CSPC OUYI PHARM CO LTD