Determination of residual organic solvents in 2-benzoylamino-n-[4-(4,6-dimethylpyrimidin-2- ylsulfamoil)-phenyl]-benzamide by gas chromatography

Relevance. Due to the active growth of the pharmaceutical industry in the Russian Federation, one of the important tasks is quality control and standardization of manufactured pharmaceutical products. During the synthesis of pharmaceutical substances, both in laboratory conditions and at large pharmaceutical enterprises, various organic solvents are used. In accordance with the requirements of ND, the determination of the content of organic solvents is a mandatory requirement in the quality control of medicinal products, thus, the development of methods for the determination of residual organic solvents is relevant for modern pharmaceutical science. The aim of the study. To develop a method for the quantitative determination of residual organic solvents in the pharmaceutical substance of 2-benzoylamino-N-[4-(4,6-dimethylpyrimidin-2-ylsulfamoyl)-phenyl]-benzamide Material and methods. Investigation was carried out using gas chromatograph "Kristall 2000M" on 5 laboratory series of the substance of 2-benzoylamino-N-[4-(4,6-dimethylpyrimidin-2-ylsulfamoyl)-phenyl]-benzamide. For the analysis of acetic acid, a packed glass column FIP-FFAP was used (length 1 m, diameter. Stationary liquid phase - FFAP in an amount of 15% of the solid support, particle size 0.255 - 0.350 mm, acetic acid peak retention time 4.5. For the analysis of the residual DMF content, we used chromatographic column M (type 11) "Chromatek" made of stainless steel with a length of 2 m and an inner diameter of 3 mm. FFAP was used as a stationary liquid phase (in an amount of 10% of the solid carrier, particle size from 0.255 to 0.350 mm, retention time of the DMF peak 5.55 min, in both cases headspace analysis was used. Results. It was found that the average content of residual solvents per 1 g of 2-benzoylamino-N-[4-(4,6-dimethylpyrimidin-2-ylsamoyl)-phenyl]-benzamide is 34.59±1.02 mg for acetic acid and 38.99±1.70 mg for dimethylformamide. Proposed method has sufficient validation characteristics as linearity, precision and trueness. Conclusions. The proposed method makes it possible to determine the residual solvents in the substance of 2-benzoylamino-N-[4-(4,6-dimethylpyrimidin-2-ylsulfamoyl)-phenyl]-benzamide and can be included in the draft regulatory document for its pharmaceutical substance.

chromatography, residual organic solvents, acetic acid, dimethylformamide, quinosalinone derivatives