SEC-RI-MALLS和SEC-RID测定丙交酯乙交酯共聚物相对分子质量及相对分子质量分布的方法比较  

Comparison of SEC-RI-MALLS and SEC-RID methods for determining molecular weight and molecular weight distribution of PLGA

作　　者：王保成 张晓艳 周小华 赵恂 马聪玉 高正松 施海蔚 袁耀佐 杭太俊[3] WANG Baocheng;ZHANG Xiaoyan;ZHOU Xiaohua;ZHAO Xun;MA Congyu;GAO Zhengsong;SHI Haiwei;YUAN Yaozuo;HANG Taijun(Nanjing Well Pharmaceutical Technology Co.,Ltd,Nanjing 210042,China;Jiangsu Institute for Food and Drug Control,Nanjing 210019,China;China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]南京威尔药业集团股份有限公司,南京210042 [2]江苏省食品药品监督检验研究院,南京210019 [3]中国药科大学,南京211198

出　　处：《中国药品标准》2025年第1期110-116,共7页Drug Standards of China

基　　金：2023年度江苏省工业和信息产业转型升级专项资金项目资助;江苏省药品监督管理局科研计划项目(202320);江苏省药品监督管理局科研计划项目(KJ2024050)。

摘　　要：目的:建立体积排阻色谱-示差折光-多角度激光光散射检测器联用(SEC-RI-MALLS)法与体积排阻色谱-示差折光检测器(SEC-RID)法测定丙交酯乙交酯共聚物(Poly(Lactide-co-Glycolide Acid),PLGA)相对分子质量及相对分子质量分布,并对两种方法的测定结果进行比较。方法:采用SEC-RI-MALLS法时,以四氢呋喃为流动相,以Shodex GPC KF-803L为色谱分离柱,以四氢呋喃为流动相,流速为1 mL·min^(-1),柱温为30℃,进样体积为100μL。采用SEC-RID法时,以四氢呋喃为流动相,以Agilent PLgel 5μm MIXD-D为色谱柱,以四氢呋喃为流动相,流速为1 mL·min^(-1),柱温为30℃,示差折光检测器温度为35℃,进样体积为20μL,使用Agilent公司GPC软件计算相对分子质量及相对分子质量的分布。对新建立的方法进行方法学验证,并采用新建方法对13批样品的相对分子质量和相对分子质量分布进行测定。结果:SEC-RI-MALLS法的精密度、准确性、稳定性、重复性试验RSD分别为1.35%、1.58%、1.53%、1.26%;SEC-RID法线性良好(r^(2)=0.9999),精密度、准确性、稳定性、重复性试验(n=6)RSD分别为2.05%、1.62%、1.30%、2.97%。SEC-RI-MALLS法的测定值比SEC-RID法的小;将SEC-RI-MALLS法测定值乘以转换系数1.5后,与SEC-RID法的测定值进行配对t检验,结果显示两种方法无显著性差异。结论:建立的两种方法均可用于PLGA相对分子质量及相对分子质量分布的测定,在实际应用过程中,可根据不同的应用场景选择适宜的方法。Objective:To establish a method for determining the molecular weight and molecular weight distribution of Poly(Lactide-co-Glycolide Acid)(PLGA)using Size Exclusion Chromatography-Refractive Index-Multiangle Laser Light Scattering(SEC-RI-MALLS)and Size Exclusion Chromatography-Refractive Index(SEC-RID),and to compare the results obtained from these two methods.Methods:For SEC-RI-MALLS,tetrahydrofuran was used as the mobile phase,Shodex GPC KF-803L was employed as the chromatographic column with a flow rate of 1 mL·min^(-1),column temperature at 30℃,and an injection volume of 100μL.For SEC-RID,tetrahydrofuran was also used as the mobile phase,Agilent PLgel 5μm MIXD-D was used as the chromatographic column with a flow rate of 1 mL·min-1,column temperature at 30℃,differential detector temperature at 35℃,and an injection volume of 20μL.The molecular weight and molecular weight distribution were calculated using Agilent′s GPC software.The newly established methods were validated methodologically,and the molecular weight and molecular weight distribution of 13 batches of samples were determined.Results:The precision,accuracy,stability,and repeatability tests for SEC-RI-MALLS showed RSD values of 1.35%,1.58%,1.53%,and 1.26%,respectively.The SEC-RID method exhibited good linearity(r^(2)=0.9999),with RSD values for precision,accuracy,stability,and repeatability tests(n=6)of 2.05%,1.62%,1.30%,and 2.97%,respectively.The results obtained from SEC-RI-MALLS were lower than those from SEC-RID,and the molecular weight distribution coefficient was smaller,but the results from the paired T-test performed with the value measured by SEC-RID method and the value measured by SEC-RI-MALLS method multiplied a conversion coefficient of 1.5 showed no significant difference between the two methods.Conclusion:Both methods are stable and reliable,and can be used for the determination of PLGA molecular weight and molecular weight distribution based on the specific situations.

关 键 词：多角度激光光散射 体积排阻色谱 示差折光检测器 丙交酯乙交酯共聚物 相对分子质量及相对分子质量分布 

分 类 号：R921.2[医药卫生—药学]