CN102564836A - Method for analyzing residual organic solvents in bulk drug - Google Patents

Abstract

The invention belongs to the field of analytical chemistry, and relates to a method for analyzing residual organic solvents in raw materials by using micro-extraction technology, in particular to a method for analyzing residual organic solvents in raw materials by ultrasonic-assisted dispersion liquid-phase micro-extraction technology. The main investigation index of the present invention is an organic solvent with low solubility in water. In this method, the bulk drug is dissolved in quantitative water, an organic solvent with a volume density larger than water is added as an extraction agent, and a dispersed liquid-phase microextraction is carried out under the assistance of ultrasonic waves for a certain period of time, centrifuged, and the lower organic solvent layer is removed, and the organic solvent layer is extracted by capillary gas chromatography. The method was used to analyze and determine the content of residual organic solvents in raw materials. The method is simple, rapid, low in cost, high in enrichment efficiency, friendly to the environment, and suitable for the determination of residual organic solvents of water-soluble drugs. Combining this method with capillary gas chromatography, it can be used to accurately determine the content of residual organic solvents in raw materials, so as to evaluate the quality of raw materials.

Description

A method for analyzing residual organic solvents in raw materials

technical field

The invention belongs to the field of analytical chemistry, and relates to a method for analyzing residual organic solvents in raw materials, in particular to a method for analyzing residual organic solvents in raw materials by using micro-extraction technology, especially using ultrasonic-assisted dispersion liquid-phase microextraction (Ultrasound-assisted Dispersive Liquid–Liquid Microextraction, UA-DLLME) technology analysis method for residual organic solvents in raw materials.

Background technique

Residual solvents in drugs refer to the organic solvents that are used or generated in the production of raw materials or excipients and in the preparation of preparations but cannot be completely removed. According to the International Chemical Safety Program, as well as the research results released by the U.S. Environmental Protection Agency and the World Health Organization, many organic solvents have certain hazards to the environment and the human body. environment, requires research and control of residual solvents. The 2010 edition of the "Chinese Pharmacopoeia" has clear limits on the residues of organic solvents in drugs.

Dispersive Liquid–Liquid Microextraction (DLLME) is a new environment-friendly extraction method developed abroad in recent years. Its basic principle is to extract by the distribution of analytes between the aqueous phase and the organic phase. Enrichment. Ultrasonic-assisted dispersive liquid phase microextraction (UA-DLLME) adopts ultrasonic assistance, which is conducive to the uniform dispersion of the organic phase extractant in the sample, accelerates the contact between the extractant and the sample, and also plays a certain role in the stability of the emulsification system. Integrating sampling, extraction and concentration, the operation is simple, fast, low cost, environmentally friendly and high enrichment efficiency.

At present, the methods reported for the determination of residual solvents in drugs include direct sampling gas phase method, headspace gas phase method, etc., but these methods all have the disadvantages of large amount of organic solvent, high extraction cost, and no enrichment effect. Therefore, there is a need in this field to establish a simple, fast, low-cost, environmentally friendly, and high-enrichment method to facilitate the separation and analysis of residual solvents in drugs.

Contents of the invention

The purpose of the present invention is to provide a method for analyzing residual organic solvents in raw materials, in particular to a method for analyzing residual organic solvents in raw materials using microextraction technology, especially using ultrasonic-assisted dispersion liquid phase microextraction (Ultrasound-assisted Dispersive Liquid–Liquid Microextraction, UA-DLLME) technology analysis method for residual organic solvents in raw materials.

In the method of the present invention, select the organic solvent with less solubility in water as the index of method investigation.

The method of the invention uses the UA-DLLME method to extract and enrich the residual organic solvent in the medicine, and the method is simple, fast, low in cost, friendly to the environment and has high enrichment efficiency. The method, combined with capillary gas chromatography, can be used to accurately determine the content of organic solvents in medicines, so as to evaluate the quality of medicines.

Specifically, the method for analyzing the residual organic solvent in the bulk drug of the present invention is characterized in that the residual organic solvent in the drug is extracted and enriched by ultrasonic-assisted dispersion liquid phase microextraction technology, which includes the steps of:

1) Sample pretreatment:

Take the sample of the raw material drug to be tested, dissolve it in water to prepare an aqueous solution of salt with the required concentration, and add the extractant;

2) Place in an ultrasonic assisted extraction device for atomization and form a uniform emulsion;

3) Centrifuge and remove the organic solvent layer;

4) Use capillary gas chromatography to analyze and determine the content of residual organic solvents in raw materials.

In the present invention, the residual organic solvent in the bulk drug refers to an organic solvent with low solubility in water, such as ethyl formate, dichloromethane or toluene.

In the present invention, the ultrasonic assistance is to use an ultrasonic instrument to provide ultrasonic waves. In the embodiments of the present invention, the time for ultrasonic assistance is 0-30 minutes, and the ultrasonic power is 110-175w.

In the present invention, the extractant is an organic solvent that is denser than water and hardly soluble in water. In the present invention it is generally selected from chlorinated hydrocarbons.

In the embodiment of the present invention, the residual organic solvent in the drug is extracted and enriched by ultrasonic-assisted dispersion liquid phase microextraction technology, and the content of the residual organic solvent in the raw drug is analyzed:

Take an appropriate amount of sample, dissolve it in an aqueous salt solution, add a certain amount of extractant, place it in an ultrasonic-assisted extraction device, select the ultrasonic time and ultrasonic power, extract and centrifuge, and take the lower layer for analysis.

In the above method of extracting and enriching the residual solvent in the medicine, the aqueous salt solution used is an aqueous sodium chloride solution with a concentration range of 0.5-3 mol/L.

In the above method of extracting and enriching the residual solvent in the drug, the volume of the added extractant is 8-16 μL, which is selected from chlorobenzene, dichlorobenzene, dichloroethane, carbon tetrachloride or trichloroethylene.

In the above method of extracting and enriching the residual solvent in the medicine, the ultrasonic power used is 110-175w, and the ultrasonic-assisted extraction time is 0-30 minutes.

The advantages of the method for analyzing residual organic solvents in raw materials by using ultrasonic-assisted dispersive liquid-phase microextraction (UA-DLLME) technology in the present invention are as follows:

The method is simple, accurate, reliable, rapid, low in cost, friendly to the environment, high in enrichment efficiency, less in sample consumption, short in extraction time, good in reproducibility and high in recovery rate. Combining this method with capillary gas chromatography, it can be used to accurately determine the content of residual organic solvents in drugs, so as to evaluate the quality of drugs.

For ease of understanding, the method of the present invention will be described in detail below with specific drawings and embodiments. It should be pointed out that the specific examples and accompanying drawings are only for illustration. Obviously, those skilled in the art can make various amendments and changes within the scope of the present invention according to the description herein. These amendments and Modifications are also included within the scope of the present invention.

Description of drawings

Fig. 1 is the basic schematic diagram of UA-DLLME.

Detailed ways

Embodiment 1: The content of ethyl formate, methylene chloride and toluene in the crude drug analyzed by ultrasonic-assisted dispersion liquid phase microextraction

Instruments and materials:

Instruments: Agilent 6890 Gas Chromatograph of Hewlett-Packard Company (including HP Chromatographic Workstation, Autosampler, Hydrogen Flame Ionization Detector), Branson B550DTH Ultrasonic Instrument, Thermo Scientific Microcl 17R Centrifuge, Millipore Direct-Q Purified Water generator.

Material: SM23 API (batch number: 20090921). Sodium chloride and dichloroethane are analytically pure, deionized pure water is produced by Millipore Direct-Q pure water generator, ethyl formate, dichloromethane and toluene standard products are from China Pharmaceutical (Group) Chemical Reagent Co., Ltd. company.

Sample pretreatment:

Take 30mg sample, dissolve it in 0.5mL, 1mol/L sodium chloride aqueous solution, put it in a 1.5ml centrifuge tube, add 10μL dichloroethane, put the centrifuge tube in an ultrasonic-assisted extraction device, the ultrasonic power is 175w, ultrasonic 2min, take out the centrifuge tube, centrifuge 4min under the rotating speed of 4000rpm, take off the lower layer and inject and analyze, obtain the assay result of the content of ethyl formate, dichloromethane and toluene in the crude drug.

The experimental results show that, compared with the prior art, the method is simple, fast, low in cost, high in enrichment efficiency, friendly to the environment, and can accurately determine the content of residual organic solvents in the raw materials, so as to evaluate the quality of the raw materials.

Claims (8)

1. a method of analyzing residual organic solvent in the bulk drug is characterized in that, utilizes ultrasound wave aid dispersion liquid-phase micro-extraction technology with extraction of the residual organic solvent in the medicine and enrichment, and it comprises step:

1) sample pre-treatments:

Get bulk drug sample to be measured, dissolving is mixed with the WS of the salt of desired concn in the water, adds extractant;

2) be positioned over and atomize in the ultrasound wave assisted extraction device and form homogeneous latex emulsion;

3) centrifugal, take off a layer organic solvent layer;

4) with the content of residual organic solvent in the capillary gas chromatography assay determination bulk drug.

2. by the method for residual organic solvent in the described analysis bulk drug of claim 1, it is characterized in that residual organic solvent is the less organic solvent of solubleness in water in the described bulk drug, is selected from ethyl formate, methylene chloride or toluene.

3. by the method for residual organic solvent in the described analysis bulk drug of claim 1, it is characterized in that the WS of described salt is sodium-chloride water solution, concentration range is 0.5-3mol/L.

4. by the method for residual organic solvent in the described analysis bulk drug of claim 1, it is characterized in that described ultrasound wave is auxiliary, is to adopt ultrasonic instrument that ultrasound wave is provided, and the auxiliary time of ultrasound wave is 0-30 minute, and ultrasonic power is 110-175w.

5. by the method for residual organic solvent in the described analysis bulk drug of claim 1, it is characterized in that described extractant is the organic solvent that density is bigger than water, be insoluble in water.

6. by the method for residual organic solvent in the described analysis bulk drug of claim 5, it is characterized in that described extractant extractant volume is 8-16 μ L.

7. by the method for residual organic solvent in the described analysis bulk drug of claim 5, it is characterized in that described extractant is a chlorinated hydrocarbon.

8. by the method for residual organic solvent in the described analysis bulk drug of claim 5, it is characterized in that described extractant is selected from chlorobenzene, dichloro-benzenes, ethylene dichloride, phenixin or triclene.

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