多肽微球注射剂中甘露醇含量测定研究

Research on determination of mannitol in injectable peptide microspheres

目的:建立高效液相色谱-示差折光法测定注射用醋酸亮丙瑞林和醋酸奥曲肽微球中甘露醇含量。方法:采用Phenomenex Rezex RHM-Monosaccharide H+(8%)强阳离子交换色谱柱(300 mm×7.8mm);流动相为超纯水;流速0.5 mL·min-1,检测器为示差检测器,内部温度45℃,柱温60℃,进样量20μL。结果:甘露醇进样量在1.01~50.44μg范围内线性关系良好(r2=1.000),精密度(RSD=0.15%)、稳定性(RSD=0.38%)和重复性(RSD=1.7%)良好,平均回收率为100.4%(n=9,RSD=0.89%)。醋酸亮丙瑞林微球粉末的甘露醇含量范围为3.08%~17.41%,醋酸奥曲肽微球粉末的甘露醇含量范围为16.03%~16.95%。结论:本文建立的方法适用于多肽微球注射剂中甘露醇的含量测定。

Objective:To establish an HPLC-RI method for determination of mannitol in leuprorelin acetate and octreotide acetate microspheres for injection. Methods:The Phenomenex Rezex RHM-Monosaccharide H+(8%)column(300 mm×7.8 mm) was used,the mobile phase was water at a flow rate of 0.5 mL·min-1. The detector was refractive index detector with inner temperature set at 45 ℃. The column temperature was 60 ℃,and the injection volume was 20 μL. Results:The linear range of mannitol was 1.01-50.44 μg(r2=1.000). The precision(RSD=0.15%),stability(RSD=0.38%) and repeatability(RSD=1.7%) tests were good. The average recoveries were 100.4%(n=9,RSD=0.89%). The contents of mannitol of leuprorelin acetate microspheres were among 3.08%-17.41%. The contents of mannitol of octreotide acetate microspheres were among 16.03%-16.95%. Conclusions:The established method can be used for determination of mannitol in injectable peptide microspheres.