顶空气相色谱法测定SIPI6398原料药中的九种残留溶剂

Determination of nine residual solvents in SIPI6398 API using headspace gas chromatography

目的 采用顶空气相色谱-氢火焰离子化检测(HS-GC-FID)法同时测定抗精神分裂症一类新药SIPI6398原料药中9种溶剂的残留量。方法 采用DB-1色谱柱和氢火焰离子化检测器,程序升温方法检测。检测器温度为250℃,进样口温度为250℃,载气为高纯氮气,流速为25 mL·min^(-1),分流比为20∶1,分流进样和顶空进样,平衡时间为30 min,加热箱温度为95℃,定量环温度为105℃,传输线温度为115℃。结果 9种检测残留溶剂在一定浓度范围内显示良好的线性(r>0.99),溶剂甲醇、乙醇、乙腈、二氯甲烷、四氢呋喃、乙酸乙酯、三乙胺、正庚烷、N,N-二甲基甲酰胺的定量限分别为60.490、99.810、16.015、24.150、14.450、25.235、6.225、25.775、38.835μg·mL^(-1);平均回收率均在80%~120%之间,RSD值均小于10%,符合要求。结论 本法专属、灵敏、准确、稳定,可用于SIPI6398原料药中9种残留溶剂的测定,同时也为其他药物相同残留溶剂的测定提供有益参考。

A Headspace gas chromatography-hydrogen flame ionization detection(GC-FID) method was established for the determination of nine residual solvents in SIPI6398 API simultaneously, which obtained the notice of clinical trial approval for anti-schizophrenia.DB-1 chromatographic column, hydrogen flame ionization detector and temperature programmed method were used for detection.The detector temperature was 250 ℃,the inlet temperature was 250 ℃,the carrier gas was high purity nitrogen, carrier gas flow rate was 25 mL·min^(-1),the split ratio was 20∶1,the split injection and headspace injection, the balance time was 30 min, the heating box temperature was 95 ℃,the quantitative ring temperature was 105 ℃,and the transmission line temperature was 115 ℃.The results indicated that each of the nine residual solvents had good linearity within a certain concentration range(r>0.99).The limits of quantification of methanol, ethanol, acetonitrile, dichloromethane, tetrahydrofuran, ethyl acetate, triethyl amine, n-heptane, and N,N-dimethylformamide were 60.490,99.81,16.015,24.150,14.450,25.235,6.225,25.775,38.835 μg·mL^(-1),respectively.The average recovery of each residual solvent was between 80%-120%,and RSD were less than 10%,in line with the requirements.This method was exclusive, sensitive, reliable and accurate, can be used for the determination of nine residual solvents in SIPI6398 API,simultaneously.At the same time, it can also provide some useful reference for the determination of the same residual solvents in other drugs.