玻璃酸钠特性黏数与相对分子质量测定研究  

Investigaotion on the determination of intrinsic viscosity and relative molecular mass of sodium hyaluronate

作　　者：赵海云 张冬梅 王春芳 刘文坤 杨蕙如 陈德俊 ZHAO Haiyun;ZHANG Dongmei;WANG Chunfang;LIU Wenkun;YANG Huiru;CHEN Dejun(Shandong Institute For Food and Drug Control,NMPA Key Laboratory for Research and Evaluation of Generic Drugs,Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs,Jinan 250101,China;Shandong Center For Food and Drug Evaluation&Inspection,Jinan 250013,China)

机构地区：[1]山东省食品药品检验研究院,国家药品监督管理局仿制药研究与评价重点实验室,山东省仿制药一致性评价工程技术研究中心,济南250101 [2]山东省食品药品审评查验中心,济南250013

出　　处：《中国药品标准》2022年第5期472-478,共7页Drug Standards of China

基　　金：国家药品药用辅料标准提高(编号:2018Y027)。

摘　　要：目的:从特性黏数、相对分子质量、相对分子质量分布三个方面开展对比研究,确立合适的检测方法纳入起草标准。对比考察玻璃酸钠特性黏数与相对分子质量测定方法,并确定最优的方法对玻璃酸钠进行质控。方法:对比考察EP 10.0/BP 2020和JPⅩⅦ特性黏数测定方法。采用乌氏黏度计测定供试品溶液流出时间,经线性回归计算特性黏数;经公式转换计算平均相对分子质量。采用多角激光光散射仪(检测波长:690 nm)与示差折光检测器结合,照分子排阻色谱法,以Shodex RC804凝胶柱为色谱柱;以0.2 mol·L^(-1)氯化钠溶液为流动相,用Astra 6软件计算相对分子质量分布。照分子排阻色谱法,示差折光检测器,以0.2 mol·L^(-1)氯化钠溶液为流动相,以Shodex SB-806HQ凝胶柱为色谱柱,以6个已知相对分子质量范围25万~316万的聚苯乙烯磺酸钠盐对照品作标准曲线,计算供试品相对分子质量。结果:特性黏数测定受温度影响显著,EP 10.0/BP 2020特性黏数测定结果高于JPⅩⅦ测定结果。EP 10.0/BP 2020特性黏数计算出的平均相对分子质量与对照品法测得相对分子质量结果均偏高,由JPⅩⅦ测得特性黏数计算出的平均相对分子质量与多角激光散射-示差折光法测得结果基本一致。结论:经对比考察,采用JPⅩⅦ特性黏数测定方法,可同时获得特性黏数和平均相对分子质量,无需再单独设定相对分子质量检测项目,满足玻璃酸钠的质控要求。Objective:Comparative studies were carried out from three aspects of the characteristic viscosity number,relative molecular mass and relative molecular mass distribution,and appropriate detection methods were established to be included in the drafting standards.Methods:The method of viscosity determination of EP 10.0/BP 2020 and JPⅩⅦwas compared.The outflow time of the test solution was measured by the Uhns viscosity meter.The characteristic viscosity was calculated by linear regression.Then the average molecular mass was calculated by formula conversion.A multiangle laser light scatterer(detection wavelength:690 nm)was combined with a differential refractive detector to perform molecular exclusion chromatography.Shodex RC804 gel column was used as the chromatographic column.The relative molecular mass distribution was calculated with Astra 6 software using 0.2 mol·L^(-1) sodium chloride solution as the mobile phase,and calculatedthe relative molecular mass distribution with Astra 6 software.Size-exclusion chromatography was performed witha refractive index detector,0.2 mol·L^(-1) sodium chloride solution wasused as mobile phase,Shodex SB-806HQ gel column was used as column.The 6 known relative molecular mass of polystyrene sulfonic acid sodium salt was uesed as reference substance with ranges from 250000 to 3160000.the relative molecular mass of the sample was calculated by the standard curve.Results:The measurement of intrinsic viscosity was significantly affected by temperature,and the measurement result of EP 10.0/BP 2020 was higher than that of JPⅩⅦ.The average relative molecular mass calculated by the characteristic viscosity of EP 10.0/BP 2020 and the relative molecular mass measured by the reference method were both higher.the average molecular weight calculated by JPⅩⅦmethod was basically consistent with the molecular weight detected by multi-angle light scatter combined with refractive index detector(MALS-RI).Conclusion:Through comparative investigation,the JPⅩⅦmethod can obtain both t

关 键 词：玻璃酸钠 特性黏数 平均相对分子质量 相对分子质量 

分 类 号：R921.2[医药卫生—药学]