Method for detecting purity of 3-methylamino-1,2-propandiol by gas chromatography

Abstract

The invention provides a method for detecting the purity of 3-methylamino-1,2-propandiol by gas chromatography. The method comprises the flowing steps: preparing a sample, setting chromatographic conditions and carrying out detection; in the setting of the chromatographic conditions, the column temperature is 240 to 260 DEG C. With the adoption of the method disclosed by the invention, the content of 3-methylamino-1,2-propandiol and the contents of impurities in 3-methylamino-1,2-propandiol can be simultaneously detected and analyzed; the accuracy and precision of analysis data are improved, the repeatability is good and the sensitivity is high; the detection time is short, the operation is easy and simple, and the analysis time of an analyst is saved; the work efficiency is improved; the service life of a chromatographic column is prolonged and the cost is reduced; derivatization is not required, the sample is directly injected after being dissolved by using chromatographically pure methanol to lower the viscosity of the sample.

Description

technical field [0001] The invention relates to a method for measuring the purity of 3-methylamino-1,2-propanediol, an intermediate of non-ionic contrast agent iopromide, by gas chromatography, especially to realize the purity of each of 3-methylamino-1,2-propanediol. The separation of impurity components belongs to the technical field of product instrument analysis. Background technique [0002] 3-Methylamino-1,2-propanediol is an important raw material for the synthesis of low-osmotic non-ionic contrast agent iopromide, and its purity, quantity and content of impurities directly affect the purity and clinical application of the final product iopromide . In the synthesis reaction of iopromide, if the impurity content of 3-methylamino-1,2-propanediol is too high or the impurity components are more, it will react with the intermediate 3-(2-methoxy)acetamido]-5 -(2,3-Dihydroxy-n-propylcarbamoyl)-2,4,6-triiodobenzoyl chloride undergoes a variety of side reactions to produce a...

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Problems solved by technology

[0004] You can refer to the analysis of the same series of products 3-amino-1,2-propanediol, Wang Feng, a postgraduate student of Shandong University, in the paper "Research on the catalytic synthesis of N,N-(R_1, R_2)-3-amino-1,2-propanediol compounds "(2010) proposed the use of stainless steel chromatographic column, hydrogen as carrier gas, FID hydrogen ion flame adding detector, gas chromatography with programmed temperature detection method for 3-methylamino-1,2-propanediol, but the method has The following shortcomings: (1) The peak shape of the spectrum is too poor and the tailing is serious; (2) The impurities in it are not completely separated; (3) Although the retention time of the main peak is kept at 0.348min, other impurities are not separated at all, and only The purity of 3-methylamino-1,2-propanediol

The disadvantages of this method are: (1) trifluoroacetic anhydride reacts with other components in the sample to form derivatives, and the detection result also brings impurities in trifluoroacetic anhydride. It is difficult to guarantee the accuracy of the data due to the quantitative calculation of the content of each component; (2) The detection time is long, from sampling, to trifluoroacetic anhydride derivatization reaction to the result, it takes at least 60 minutes, and the operation is cumbersome

[0006] You can refer to the analysis of the same series of products 3-amino-1,2-propanediol. Li Qiran and Liang Yongsheng published a paper "Derivative Gas Phase Chromatographic Determination of the Content of 3-Amino-1.2-Propanediol "In ", the method for determining the content of 3-amino-1,2-propanediol by derivatization gas chromatography is established, and the sample is passed through trifluoroacetic anhydride (TFAA) at 50 ° C After derivatization for 30 minutes, use a gas chromatograph SE-54 capillary column (30m×0.25mm×0.25μm) equipped with an FID detector to measure. Although this method has good reproducibility and high accuracy, the method is simple and easy. and other advantages, but there are still the following disadvantages: (1) The detection time is long, and it takes at least 60 minutes from sampling, to the derivatization reaction of trifluoroacetic anhydride to the result; (2) Using n-hexane as the solvent, the sample is almost insoluble, The derivatization reaction of trifluoroacetic anhydride is complicated to operate under ice water conditions and the amount of n-hexane is too large; (3) trifluoroacetic anhydride reacts with other components in the sample to form derivatives, and the test results also compare trifluoroacetic anhydride to The impurities in the acid anhydride are brought in. Since this method calculates the content of each component by area normalization, the accuracy of the data is difficult to guarantee

The disadvantage of this method is that the detection requires at least 1g sample, 5mL derivatization reagent, and 5mL pyridine as a catalyst. For the tested samples, the post-processing steps are relatively complicated and the detection time is long

[0009] Through the qualitative analysis of 3-methylamino-1,2-propanediol products by GC-MS, there are still 2-methylamino-1,3-propanediol, 1,3-dimethylamino-propanol, N, N-(2,3-dihydroxypropyl) methylamine [structural formula CH 3 N(CH 2 CHOHCH 2 Oh) 2 ], glycerin, polymerized glycerin (generally 2 in the degree of polymerization) and other impurities, the analysis and detection methods provided by the prior art cannot be separated or the impurities in them cannot be separated at all

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