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Method for detecting acyl chloride in medicine or synthesized intermediate thereof by derivatization HPLC-DAD method

A technology of derivatization and derivatization reaction, which is used in the determination of acid chloride by derivatization HPLC-DAD method and the determination of acid chloride in drugs or their synthetic intermediates by derivatization HPLC-DAD method, which can solve the problems of strong ultraviolet absorption and insufficient specificity.

Inactive Publication Date: 2017-08-04
CHINA PHARM UNIV
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Problems solved by technology

[0004] Among various separation and analysis methods, the HPLC-DAD method has become the preferred method for most laboratories because of its simplicity and practicality. However, due to the strong ultraviolet absorption of most drugs and their synthetic intermediates, the lack of specificity is the reason for this. main flaw of the law

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  • Method for detecting acyl chloride in medicine or synthesized intermediate thereof by derivatization HPLC-DAD method
  • Method for detecting acyl chloride in medicine or synthesized intermediate thereof by derivatization HPLC-DAD method
  • Method for detecting acyl chloride in medicine or synthesized intermediate thereof by derivatization HPLC-DAD method

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preparation example Construction

[0047] 1.3. Solution preparation

[0048] Stock solutions of various acid chlorides: Take about 10mg of each acid chloride, accurately weigh it, put it in a 10mL measuring bottle, dilute with acetonitrile to the mark, and shake well. Each stock solution has good stability within 8 hours at room temperature.

[0049] Aniline, 2-nitroaniline (2-NA), 4-nitroaniline (4-NA), phenylhydrazine, 2-nitrophenylhydrazine (2-NPH) and 4-nitrophenylhydrazine hydrochloride (4 -NPH·HCl) test solution: Take about 20 mg of each reagent, weigh it accurately, place it in a 10 mL measuring bottle, dilute to the mark with pure acetonitrile, and shake well.

[0050] 1.4. Derivatization experimental conditions

[0051] Precisely pipette 100 μL of the acid chloride mother solution, put it in a 10 mL volumetric flask, add 500 μL of derivatization reagent and acetonitrile to dilute to the mark, and shake well. After reacting at room temperature for 1 h, 20 μL was taken and injected directly.

Embodiment 1

[0053] Taking isobutyryl chloride as a representative, derivatize it with the same concentration of aniline, 2-nitroaniline, 4-nitroaniline, phenylhydrazine, 2-nitrophenylhydrazine, and 4-nitrophenylhydrazine derivatization reagents. See 1.4 for derivatization experimental conditions. Under the same chromatographic conditions, use DAD to scan each derivatized product, record the spectrum and chromatogram of the product, and evaluate the pros and cons of the derivatized reagent with the maximum absorption wavelength and absorption intensity of the product.

[0054] figure 1 A shows that the maximum ultraviolet absorption wavelengths of the derivatized products of aniline and its isobutyryl chloride are 234nm and 241nm, respectively. And the maximum absorption wavelength of 2-nitroaniline and 4-nitroaniline red-shifted to 408nm ( figure 1 B) and 374nm ( figure 1 C). However, the peaks of their respective isobutyryl chloride derivatized products are blue-shifted and the absor...

Embodiment 2

[0058] Preparation of the test solution: Accurately weigh an appropriate amount of the drug, place it in a 10mL measuring bottle, add 500 μL of derivatization reagent, add acetonitrile to dilute to the mark, shake well, and react at room temperature for 0.5h to obtain the test solution. Take 20 μL for direct injection.

[0059] Preparation of reference solution: Precisely pipette 100 μL of acid chloride stock solutions of different concentrations, put them in a 10 mL volumetric flask, add 500 μL of derivatization reagent, add acetonitrile to dilute to the mark, shake well, and react at room temperature for 0.5 h to obtain the reference solution. Take 20 μL for direct injection.

[0060] Chromatographic conditions: Shimadzu LC 20AT liquid chromatograph (including online vacuum degasser, binary gradient pump, autosampler, column thermostat, DAD detector and LC-solution chromatographic workstation); chromatographic column: Dima Technology Co., Ltd. Diamonsil TM C18 (250mm×4.6m...

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Abstract

The invention discloses a method for detecting acyl chloride in a medicine or synthesized intermediate thereof by a derivatization HPLC-DAD method. The method comprises the following steps: derivatizing acyl chloride with a nitrophenylhydrazine derivatized reagent at room temperature to generate a product has relatively absorbability in an ultraviolet visible region; separating and detecting the derivatized product of acyl chloride in the ultraviolet visible region by using the derivatized reacting liquid as a feeding sample based on the principle of reversed-phase high-performance liquid chromatography so as to qualitatively or quantitatively detecting acyl chloride. Based on the quick reaction characteristic of acyl chloride and hydrazino and the ultraviolet visible absorption characteristic of the product generated after acyl chloride and nitrophenylhydrazine perform a biochemical reaction, interference of a medicine or the synthesized intermediate matrix thereof on acyl chloride detection can be effectively avoided, so that a simple and universal method for detecting acyl chloride in a medicine or synthesized intermediate thereof by a derivatization HPLC-DAD method can be established. Methodological verification results indicate that the method has excellent specificity and sensitivity.

Description

technical field [0001] The invention belongs to the field of drug analysis and detection, and relates to a method for determining acid chlorides by a derivatization HPLC-DAD method, in particular to a method for determining acid chlorides in drugs or their synthetic intermediates by a derivatization HPLC-DAD method. Background technique [0002] In recent years, genotoxic impurities (GTIs) in drugs have received widespread attention due to their potential carcinogenicity to humans, and they need to be controlled at a safe level [1] . Gas chromatography (GC), high performance liquid chromatography (HPLC) or capillary electrophoresis chromatography (CE) coupled with mass spectrometry (MS) play an important role in the analysis of genotoxic impurities [2-3] . Some analytical strategies such as chemical derivatization [4] Can improve analyte detectability, or Design of Experiments (DoE) [5] Can assist with system optimization of method conditions. Acid chlorides are importa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/89
CPCG01N30/89
Inventor 郑枫郑项元徐然柳文媛
Owner CHINA PHARM UNIV
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