Method for analyzing genotoxic impurities in moxifloxacin hydrochloride starting material

A technology of moxifloxacin hydrochloride and genotoxicity, which is applied in the directions of material separation, analysis materials, instruments, etc., can solve the problems such as no published reports on the determination method of genotoxic impurities.

Active Publication Date: 2020-10-30
SHANDONG INST FOR FOOD & DRUG CONTROL +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no published report on the determination method of genotoxic impurities in the starting material of moxifloxacin hydrochloride

Method used

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  • Method for analyzing genotoxic impurities in moxifloxacin hydrochloride starting material
  • Method for analyzing genotoxic impurities in moxifloxacin hydrochloride starting material
  • Method for analyzing genotoxic impurities in moxifloxacin hydrochloride starting material

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] The investigation of embodiment 1 derivatization temperature

[0048] 1. Sample pretreatment

[0049] The test product (100% limit spiked) solution: take moxifloxacin hydrochloride starting material 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo -1 g of ethyl 3-quinolinecarboxylate, accurately weighed, put in a 50 ml measuring bottle, and accurately add the stock solution of impurity 2,4,5-trifluoro-3-methoxybenzoyl chloride (1.68 μg / ml) 2 ml, mix well, then precisely add 10 ml absolute ethanol, mix well. Prepare 3 copies in the same way, place them at 25°C, 30°C, and 35°C for 30 minutes, dissolve and dilute to the mark with dichloromethane, shake well, and obtain.

[0050] 2. Chromatographic conditions

[0051] Instrument: gas chromatography-mass spectrometry; chromatographic column: TG-5 ms (30 m × 0.25 mm × 0.25 μm); temperature program, the initial temperature is 100 ° C, maintained for 5 minutes, and the temperature is raised to 150 ° C at a rate of 10 ...

Embodiment 2

[0056] The investigation of embodiment 2 derivation time

[0057] 1. Sample pretreatment

[0058] The test product (100% limit spiked) solution: take moxifloxacin hydrochloride starting material 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo -1 g of ethyl 3-quinolinecarboxylate, accurately weighed, put in a 50 ml measuring bottle, and accurately add the stock solution of impurity 2,4,5-trifluoro-3-methoxybenzoyl chloride (1.68 μg / ml) 2 ml, mix well, then precisely add 10ml of absolute ethanol, mix well. Prepare 3 parts in the same way, place them in a water bath at 30°C for 5 minutes, 10 minutes, and 15 minutes respectively, dissolve and dilute to the mark with dichloromethane, shake well, and obtain.

[0059] Determine according to the chromatographic conditions set in Example 1.

[0060] 2. Results and conclusions

[0061] Table 2 Screening results of derivation time

[0062]

[0063] Conclusion: As can be seen from Table 2, the longer the derivatization tim...

Embodiment 3

[0064] Example 3 Investigation of the volume-to-mass ratio of the derivatization reagent to the moxifloxacin hydrochloride starting material

[0065] 1. Sample pretreatment

[0066] The test product (100% limit spiked) solution: take moxifloxacin hydrochloride starting material 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo - 1g of ethyl 3-quinolinecarboxylate, accurately weighed, put in a 50ml measuring bottle, and accurately add the stock solution of impurity 2,4,5-trifluoro-3-methoxybenzoyl chloride (1.68 μg / ml) 2ml, mix well, prepare 3 parts in the same way, then add 2ml, 5ml, 10ml of absolute ethanol respectively, and mix well. Heat in a water bath at 30°C for 10 minutes, dissolve and dilute to the mark with dichloromethane, shake well, and obtain.

[0067] The determination was carried out according to the chromatographic conditions determined in Example 1.

[0068] 2. Results and conclusions

[0069] Table 3 Screening results of derivatization reagent to sub...

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Abstract

The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a quantitative analysis method for potential genotoxic impurities in moxifloxacin hydrochloride starting raw material 1-cyclopropyl-6, 7-difluoro-1, 4-dihydro-8-methoxy-4-oxo-3-quinoline carboxylic acid ethyl ester, and the structure types of the potential genotoxic impurities comprise acyl halidesand unsaturated ketones. According to the invention, absolute ethyl alcohol and 2, 4-dichlorophenol are adopted; the method comprises the following steps: carrying out a derivatization reaction on 2,4, 5-trifluoro-3-methoxybenzoyl chloride to generate ethyl 2, 4, 5-trifluoro-3-methoxybenzoate, and carrying out separation and mass spectrometry detection by adopting (5% phenyl)-methyl polysiloxaneas a fixed phase derivative ethyl 2, 4, 5-trifluoro-3-methoxybenzoate and an impurity ethyl 3-(N, N-dimethylamino) acrylate. The method not only can realize effective separation of potential genotoxic impurities in the initial raw material, but also can quantitatively detect the genotoxic impurities, is simple, convenient and rapid to operate, strong in specificity, high in sensitivity, accurateand reliable, and has important significance for quality control and medication safety of moxifloxacin hydrochloride raw materials and preparations.

Description

technical field [0001] The invention relates to the technical field of drug analysis, in particular to a derivatization gas chromatography-mass spectrometry analysis method for potential genotoxic impurities, which is used for moxifloxacin hydrochloride starting material 1-cyclopropyl-6,7-difluoro-1 , Potential genotoxic impurities 2,4,5-trifluoro-3-methoxybenzoyl chloride and 3- Analysis and detection of (N,N-dimethylamino) ethyl acrylate. Background technique [0002] Moxifloxacin hydrochloride, the chemical name is 1-cyclopropyl-7-{S,S-2,8-diazo-bicyclo[4.3.0]nonan-8-yl}-6-fluoro -8-Methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylate hydrochloride, molecular formula C 21 h 24 FN 3 o 4 HCl, its structural formula is: [0003] [0004] Moxifloxacin hydrochloride is an 8-methoxyfluoroquinolone antibacterial drug with broad-spectrum and antibacterial activity, mainly used in the treatment of upper and lower respiratory tract infections (such as: acute sinusitis, acute e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/06G01N30/72
CPCG01N30/02G01N30/06G01N30/72G01N2030/067
Inventor 文松松徐玉文牛冲郭常川张雷刘琦郑静向宇杨书娟
Owner SHANDONG INST FOR FOOD & DRUG CONTROL
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