顶空气相色谱法测定Selexipag合成中间体的残留溶剂
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河北省药监局食品药品安全项目(ZD2015025)


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

    为了更好地控制Selexipag的产品质量,保证用药安全,建立了顶空气相色谱法,对Selexipag两个中间体4-[(5,6-二苯基吡嗪-2基)(异丙基)氨基]-1-丁醇(S5)和N-(2-氯乙酰基)甲基磺酰胺(S7)合成过程中残留的溶剂量进行检测。色谱柱为Kromat PC-624(V)(30.0 m×0.32 mm×18 μm)毛细管柱,程序升温方式,FID检测器温度为250 ℃,进样口温度为200 ℃,顶空瓶平衡温度为80 ℃,顶空瓶平衡时间为30 min,两个中间体所涉及的溶剂包括甲醇、乙醇、二氯甲烷、丙酮、乙酸异丙酯、甲苯及四氢呋喃。结果表明,在此色谱条件下被测溶剂完全分离,各溶剂标准曲线相关系数r2均大于0.997,平均回收率为 95.1%~106.2%,精密度、稳定性及重复性的RSD值范围为1.78%~4.60%。气相色谱法操作简单,准确度、灵敏度高,可用于检测Selexipag 原料药中残留的有机溶剂,为其中间体的质量控制提供科学依据。

    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-\[(5, 6-diphenylpyrazin -2-yl) (isopropyl) amino\]-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.

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齐海娟,崔浩亮,邓晓晴,王洪朋,高双双,哈 婧.顶空气相色谱法测定Selexipag合成中间体的残留溶剂[J].河北科技大学学报,2019,40(3):226-232

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  • 收稿日期:2019-01-15
  • 最后修改日期:2019-03-25
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  • 在线发布日期: 2019-06-27
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