Determination of residual solvents in synthetic intermediate of Selexipag by headspace gas chromatograhy

Abstract

In order to better control the quality of Selexipag products and ensure drug safety,headspace gas chromatography is established to detect the amount of solvent remaining in the synthesis of Selexipag intermediates 4-\ pyrazin -2-yl) (isopropyl) amino\]-1-butanol (S5) and N-(2-chloroacetyl) methyl sulfonamide (S7). Gas chromatography is adopted with Kromat PC-624(V) capillary column (30.0 m×0.32 mm×18 μm). The FID detector temperature and injection port temperature are 250 ℃ and 200 ℃, respectively. The headspace sampling is used at temperature 80 ℃ for 30 min. The solvents revolved are methanol, ethanol, acetone, dichloromethane, isopropylacetate, tetrahydrofuran and methylbenzene. The tested component could be completely separated under the chromatographic conditions. The correlation coefficient of each solvent standard curve is greater than 0.997 and the mean recoveries of all components are in range of 95.1%~106.2%. The RSD values of precision, stability and repeatability range from 1.78% to 4.60%. The analytical method is simple, accurate and sensitive, and it can be used for the determination of residual solvents in Selexipag, which provides scientific basis for the quality control of intermediates.

Keywords

• chromatographic analysis
• headspace gas chromatography
• residual solvent
• Selexipag
• intermediate
• content determination