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Method for determining content of bromoethane in Etazocine hydrobromide intermediate

A technology of etazocine hydrobromide and intermediates, which is applied in the field of drug analysis, can solve the problems of low recovery rate of bromoethane, does not meet detection requirements, etc., and achieves simple and convenient determination process, high accuracy, and precise sample introduction. good effect

Pending Publication Date: 2022-03-25
深圳万乐药业有限公司
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

But when adopting above-mentioned method to carry out content determination of ethyl bromide in ethazocine intermediate compound II, ethyl bromide recovery rate is low, only about 75%, does not meet detection requirement

Method used

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  • Method for determining content of bromoethane in Etazocine hydrobromide intermediate
  • Method for determining content of bromoethane in Etazocine hydrobromide intermediate
  • Method for determining content of bromoethane in Etazocine hydrobromide intermediate

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] The mensuration of bromoethane content in the compound II of embodiment 1

[0025] 1) Chromatographic conditions:

[0026] Gas chromatograph: Agilent 7890A gas chromatograph (with headspace autosampler);

[0027] Detector: FID;

[0028] Gas chromatography column: DB-624 capillary column (30m×320μm, 1.8μm);

[0029] Carrier gas: nitrogen;

[0030] Carrier gas flow rate: 1.0ml / min;

[0031] Hydrogen flow rate: 30ml / min;

[0032] Air flow rate: 300ml / min;

[0033] Column oven temperature rise program: initial 40°C, keep for 10min, then raise the temperature to 200°C at a rate of 40°C per minute, keep for 4min;

[0034] Injection port temperature: 220°C;

[0035] Detector temperature: 260°C;

[0036] Split ratio: 10:1;

[0037] Headspace equilibrium temperature: 80°C.

[0038] Headspace equilibration time: 25min.

[0039] 2) Sample solution preparation:

[0040] Preparation of the reference substance solution: Accurately weigh about 10 mg of ethyl bromide, put i...

Embodiment 2

[0043] Embodiment 2 method verification experiment

[0044] 1) Chromatographic conditions

[0045] Instrument: Agilent 7890A gas chromatograph (additional Agilent 7891A headspace autosampler)

[0046] Detector: FID detector

[0047] Chromatographic column: DB-624 capillary column (30m×320μm, 1.8μm)

[0048] Flow rate: 1.0ml / min

[0049] Hydrogen: 30ml / min

[0050] Air: 300ml / min

[0051] Carrier gas: nitrogen

[0052] Heating program: initially at 40°C, keep for 10 minutes, then raise the temperature to 200°C at a rate of 40°C per minute, and keep for 4 minutes.

[0053] Injector temperature: 220°C

[0054] Detector temperature: 260°C

[0055] Split ratio: 10:1

[0056] The headspace equilibration temperature was 80°C, and the equilibration time was 25 minutes.

[0057] 2) Preparation of solution

[0058] Blank solution: Accurately measure 1ml of N,N-dimethylformamide and 1ml of 48% hydrobromic acid, put it in a 20ml headspace bottle, seal it, shake well, and use it...

Embodiment 3

[0091] Embodiment 3 Different sample processing method recoveries difference

[0092] Investigate the recoveries of three kinds of samples prepared by untreated, treated with acetic acid and treated with hydrobromic acid to test the content of ethyl bromide.

[0093] 1) Chromatographic conditions:

[0094] Gas chromatograph: headspace autosampler;

[0095] Detector: FID;

[0096] Gas chromatography column: DB-624 capillary column (30m×320μm, 1.8μm);

[0097] Carrier gas: nitrogen;

[0098] Carrier gas flow rate: 1.0ml / min;

[0099] Hydrogen flow rate: 30ml / min;

[0100] Air flow rate: 300ml / min;

[0101] The temperature rise program of the column oven: the initial column temperature is 40°C and kept for 10 minutes, then the temperature is raised to 200°C at a rate of 40°C per minute, and kept for 4 minutes;

[0102] Injection port temperature: 220°C;

[0103] Detector temperature: 260°C;

[0104] Split ratio: 10:1;

[0105] Headspace equilibrium temperature: 80°C;

...

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Abstract

The invention provides a method for determining bromoethane in an intermediate for synthesizing Etazocine hydrobromide, namely a compound II, which comprises the following steps: adding a hydrogen bromide solution into the compound II to be detected, uniformly shaking at room temperature to completely convert the compound II into a more stable substance which does not react with bromoethane, and preparing a test solution. According to the present invention, the headspace sample injection gas chromatography is adopted to determine, the residual amount of bromoethane in the Etazocine intermediate (compound II) is calculated by using the peak area external standard method, the method has advantages of good specificity, good linearity, good sample injection precision, simple and convenient determination process, high experimental result accuracy, no influence of the small change of the gas chromatography parameter in the experiment, and good repeatability, and can be used for the detection of the residual amount of bromoethane in the Etazocine intermediate (compound II). The method can accurately measure the amount of residual bromoethane in the Etazocine intermediate compound II, and can be used for quality control in the synthesis process of an Etazocine hydrobromide bulk drug.

Description

technical field [0001] The invention belongs to the field of drug analysis, and in particular relates to a method for determining the content of ethyl bromide in a key intermediate for synthesizing etazocine hydrobromide crude drug. Background technique [0002] Eptazocine hydrobromide was originally developed by Nihon lyakuhin Kogyo Co., Ltd. and was launched in Japan in 1987. It is mainly used for the treatment of postoperative pain and cancer pain. Eptazocine hydrobromide Xin is a partial agonist of opioid receptors, acts on K receptors, uses selective antagonists to block postsynaptic receptors, and blocks chemical messengers that transmit pain information. In terms of analgesia, the analgesic efficacy of ethazocine is 1-2 times that of pentazocine. Its structural formula is as follows (compound I): [0003] [0004] Chinese patent CN104356065B discloses the synthetic method of etazocine hydrobromide, by (-)-(1S, 6S)-2,3,4,5,6,7-hexahydro-1,4-dimethyl- 1,6-endometh...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/06
CPCG01N30/02G01N30/06G01N2030/025
Inventor 袁婉刘东华吴子强袁文于玉根
Owner 深圳万乐药业有限公司
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