基于单粒子光学传感技术的光阻法用于脂肪乳注射液大于5μm的尾部大粒子控制

目的: 建立基于单粒子光学传感技术的光阻法(LE/SPOS法),对脂肪乳静脉注射液中乳滴粒径大于5 μm的尾部大粒子进行准确控制.方法: 采用EXT模式(1.8~50 μm),稀释流速60 mL·min^-1,目标粒子数2000 个·mL^-1,进样量0.98 mL,对仪器校正和检定后,分别对系统适用性、样品测定的精密度和中间精密度、回收率等方法学进行系统考察,并对多批乳剂样品进行检测.结果: 5、10、25 μm标准粒子测得的粒径大小和颗粒数均在标称值6%以内;不同PFAT₅水平的脂肪乳样品测定的RSD≤5%,2台仪器测定的RSD<10%,低、中、高3个PFAT₅水平的5 μm标准粒子平均回收率为100.5%,RSD<2.0%(n=6);8批乳剂样品PFAT₅测得值在0.010%~0.066%.结论: 建立的光阻法操作简便,符合方法学考察要求,能够对脂肪乳静脉注射液中的PFAT₅进行准确定量.

Objective: To establish a light blockage method based on a single particle optical sizing(LE/SPOS)technique for determination of the extent of the large-diameter droplet tail(>5 μm)of lipid injectable emulsions. Methods: The samples were performed under EXT mode(1.8-50 μm).The diluent flow rate was set at 60 mL·min^-1.The target particle number was set at 2000 piece·mL^-1.The injection volume was 0.98 mL.After calibration and verification of the instruments, the systematic investigation was conducted on system suitability, assay precision, intermediate precision and recovery for multiple batches of emulsions. Results: The system was suitable as the mean diameter and the number of particles coincided with the expected values by determination with 5 μm, 10 μm, and 25 μm standard particles, within a 6% acceptable error.The RSD for assay of emulsion samples at different PFAT₅levels was ≤5%, and the RSD for the two instruments was less than 10%.The average recovery for 5 μm standard particles at low, medium and high PFAT₅levels was 100.5%, and RSD was less than 2.0%.The PFAT₅ measurements of 8 batches of lipid injectable emulsions were within the range of 0.010%-0.066%. Conclusion: This method is simple to operate and meets the requirements of methodological verification, and can be used for the determination of PFAT₅ of the lipid injectable emulsions.

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