顶空气相色谱法检测水溶性SHR0410中多种水溶性差的残留溶剂

Determination of Poor Water-Soluble Residual Solvents in Water-Soluble SHR0410 by Head⁃space Gas Chromatography

目的:建立水溶性样品SHR0410原料药中3种水溶性差的残留溶剂二氯甲烷、异丙醚、三异丙基硅烷的测定方法,为SHR0410原料药中这3种残留溶剂风险评估打下基础。方法:采用顶空气相色谱外标法,色谱柱为CP-Volamine(30 m×0.32 mm)型毛细管柱,载气为氮气,氢火焰离子化检测器,柱温程序升温。结果:3种残留溶剂二氯甲烷、异丙醚和三异丙基硅烷,在此条件下能有效分离,线性范围分别为16.58~99.50μg·mL^(-1)(r=0.999)、2.47~14.83μg·mL^(-1)(r=0.999)、123.24~739.46μg·mL^(-1)(r=0.998),平均回收率分别为97.2%(RSD=2.3%,n=6)、95.5%(RSD=2.0%,n=6)、99.6%(RSD=1.4%,n=6),检测限(LOD)分别为0.07μg·mL^(-1)、0.01μg·mL^(-1)、0.005μg·mL^(-1)。对3批样品进行检验,均未检出以上3种残留溶剂。结论:该方法适用于测定水溶性SHR0410原料药样品中水溶性差的残留溶剂。

Objective:Toestablish a method for the determination of methylene chloride,isopropyl ether and triisopropyl silane,three kinds of residual solvents with poor water solubility in SHR0410 API,and lay a foundation for the risk assessment of these three residual solvents in SHR0410 API.Methods:TheHeadspace gas chromatography external standard methodwas used.The capillary columnwas CP-Volamine(30 m×0.32 mm),and with nitrogen as the carriergas and an FID as the detector.The column temperature was pro-grammed raising.Results:Thechromatographic peaksofthe three residual solvents dichloromethane,isopropyl ether and triisopropyl silane can be effectively separated under this condition.The linear ranges for methylene chloride,isopropyl ether and triisopropyl silane were16.58-99.50μg·mL^(-1)(r=0.999),2.47-14.83μg·mL^(-1)(r=0.999),123.24-739.46μg·mL^(-1)(r=0.998)respectively.The aver-age recoverieswere 97.2%(RSD%=2.3%,n=6),95.5%(RSD%=2.0%,n=6),99.6%(RSD%=1.4%,n=6),respectively,and the LOD were 0.07μg·mL-1,0.01μg·mL^(-1),0.005μg·mL^(-1) respectively.Three batches of samples were tested and noneof the above three residual solvents was detected.Conclusion:The methodestablishedcan be used for the determination of residual solvents with poor water solubility in SHR0410 API samples.