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Detection method of demethylated itopride nitrosamine

A technology of methyl-itopia nitramine and a detection method is applied in the detection field of desmethyl-itopia nitramine, can solve the problems of lack of data and the like, and achieves the effects of high sensitivity and good separation effect of the method

Pending Publication Date: 2021-11-30
珠海润都制药股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, desmethylitopride nitramine is a new impurity, and there is almost no information about it in existing reports

Method used

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  • Detection method of demethylated itopride nitrosamine
  • Detection method of demethylated itopride nitrosamine
  • Detection method of demethylated itopride nitrosamine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] The preparation of demethyl itopride nitramine is carried out according to the following reaction.

[0018]

[0019] Dissolve about 344mg of demethylitopride in 30mL of 1M HCl aqueous solution at room temperature, and slowly add 173mg of solid sodium nitrite, fully stir and dissolve, and react at room temperature for 3 hours. After the reaction was completed, it was extracted with dichloromethane, dried over sodium sulfate, filtered, and spin-dried to obtain about 296 mg of desmethyl-itopride nitramine as a solid.

[0020] 1 H NMR (400MHz, DMSO- d6 )δ 8.85 (t, J = 5.9 Hz, 1H ), 7.52 (dd, J = 8.4 Hz, J = 2.1 Hz 1H ), 7.48 (d, J = 2.1 Hz, 1H ), 7.24(m, 2H ), 7.01 (d, J= 8.4 Hz, 1H ), 6.90 (m, 2H ), 4.50 (m, 2H ), 4.40 (d, J = 5.9 Hz, 2H ), 4.29(m, 2H), 3.80 (d, J = 1.7, 6H), 3.05 (s, 2H).

[0021] 13 C NMR (100MHz, DMSO- d6 ) Δ165.6, 156.84, 156.78, 151.2, 148.2, 132.48,132.47, 128.7, 126.6, 114.5, 114.3, 110.9, 110.6, 63.5, 55.6,55.5, 52.3, 42.0, 40.0, 39.8, 39....

Embodiment 2

[0024] System Suitability Experiment

[0025] Solution preparation:

[0026] Diluent: Acetonitrile

[0027] Take a 15ml centrifuge tube, add 5.0ml of water and 5.0ml of acetonitrile, mix well, then add about 1.0g of anhydrous sodium sulfate, shake up and down 30 times immediately, vortex for 1min, let stand for 10min, take the upper layer to get a blank solution;

[0028] Take about 25mg of demethyl itopride nitramine reference substance, accurately weigh it, put it in a 25ml measuring bottle, add acetonitrile to dissolve and dilute to the mark, shake well; then accurately measure 200µl of the above solution, put it in a 25ml measuring bottle , add acetonitrile to dilute to the mark, and shake well; then accurately measure 200 µl of the above solution, put it in a 25ml measuring bottle, add acetonitrile to dilute to the mark, shake well to obtain a stock solution of demethylitopria nitramine. (64ng / ml).

[0029] Precisely measure 2.5ml of the stock solution of demethyl itop...

Embodiment 3

[0040] specificity experiment

[0041] Solution preparation:

[0042] Diluent: acetonitrile;

[0043] Blank solution: Take a 15ml centrifuge tube, add 5.0ml of water and 5.0ml of acetonitrile, mix well, then add about 1.0g of anhydrous sodium sulfate, shake up and down 30 times immediately, vortex for 1min, let stand for 10min, and take the upper layer.

[0044] Demethyl itopride nitramine stock solution: take about 25 mg of demethyl itopride nitramine reference substance, weigh it accurately, put it in a 25ml measuring bottle, add acetonitrile to dissolve and dilute to the mark, shake well; Then precisely measure 200µl of the above solution, put it in a 25ml measuring bottle, add acetonitrile to dilute to the mark, and shake well; then precisely measure 200µl of the above solution, put it in a 25ml measuring bottle, add acetonitrile to dilute to the mark, and shake well. (Concentration: 64ng / ml)

[0045] Reference substance stock solution: Accurately measure 2.5ml of demet...

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Abstract

The invention provides a detection method of an impurity demethylated itopride nitrosamine in itopride hydrochloride, wherein the method comprises the steps: selecting octadecylsilane chemically bonded silica as a filler, and an ammonium acetate aqueous solution and acetonitrile as mobile phases to carry out liquid chromatography separation, and detecting target molecules by using combination of mass spectrometry. According to the method, the system applicability, specificity, precision, quantitation limit, detection limit, linearity and range all meet the requirements, the separation effect is good, operation is easy and convenient, and the method sensitivity is high.

Description

technical field [0001] The invention relates to the technical field of drug analysis, in particular to a method for detecting desmethyl-itopride nitramine. Background technique [0002] Itopride is a gastric motility-promoting drug that can be taken orally, and was first developed by Hokuriku Pharmaceutical Co., Ltd. Its standard name is N-[4-[2-(N,N-dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide (CAS No.: 122892-31-3 ), the chemical structure is as follows: . In the preparation process of itopride, various impurities will inevitably be produced. After research, one of the impurities was discovered, desmethyl itopria nitramine. Its standard name is N-[4-[2-(N-nitroso, N-methylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide, and its chemical structure is as follows Show: Desmethyl itopride nitramine has an N-nitroso structure. [0003] It is well known that most of such compounds with nitrosamine structures are genotoxic, such as NDMA (N-nitrosodimethylamine), NDEA ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/72G01N30/74
CPCG01N30/02G01N30/72G01N30/74
Inventor 李达胜张榕芳李厚俭覃志俊谢立
Owner 珠海润都制药股份有限公司
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