盐酸氨基葡萄糖片中吡嗪类杂质含量测定及成因分析  

Content Determination and Cause Analysis of Pyrazine Impurities in Glucosamine Hydrochloride Tablets

作　　者：王琼芬 倪东宇 张梦奇 李彬 石婧 徐虹 WANG Qiongfen;NI Dongyu;ZHANG Mengqi;LI Bin;SHI Jing;XU Hong(Zhoushan Institute for Food and Drug Control,Zhoushan,Zhejiang,China 316000)

机构地区：[1]浙江省舟山市食品药品检验检测研究院,浙江舟山316000

出　　处：《中国药业》2023年第18期72-77,共6页China Pharmaceuticals

基　　金：浙江省药品监督系统科技计划项目[2021004]。

摘　　要：目的建立测定盐酸氨基葡萄糖片中吡嗪类杂质含量的高效液相色谱法,并探讨杂质形成的影响因素。方法色谱柱为Shim-pack GIST C_(18)柱(150 mm×4.6 mm,3μm),流动相为0.05%庚烷磺酸钠溶液-乙腈(20∶1,V/V),流速为0.8 mL/min,检测波长为195 nm,柱温为35℃,进样量为10μL。考察果糖嗪及脱氧果糖嗪在不同温度(50,60,70,80℃)及相对湿度(RH,60%、75%、92%)条件下的含量变化规律。结果果糖嗪、脱氧果糖嗪质量浓度分别在0.18~9.23μg/mL和0.98~49.26μg/mL范围内与峰面积线性关系良好(r>0.9997);定量限分别为0.92 ng和0.99 ng,检测限分别为0.37 ng和0.33 ng;精密度、稳定性、重复性试验结果的RSD均小于2.0%;平均回收率分别为98.77%和99.43%,RSD分别为0.77%和0.27%(n=9)。2种杂质含量均与加热温度及RH呈显著正相关,且脱氧果糖嗪含量变化规律符合零级动力学;80℃条件下最高含量分别为加热前含量的1.5倍、3.7倍;40℃时,92%RH条件下最高含量分别为60%RH条件下的10倍、1.6倍。结论所建立的方法操作简便、结果准确,精密度、稳定性、重复性均较好,可用于盐酸氨基葡萄糖片中吡嗪类杂质的含量测定。高温、高湿条件分别对制剂中脱氧果糖嗪、果糖嗪含量影响较大。Objective To establish a high-performance liquid chromatography(HPLC)method for the determination of pyrazine impurities in Glucosamine Hydrochloride Tablets,and to investigate the influencing factors of impurity formation.Methods The chromatographic column was Shim-pack GIST C_(18) column(150 mm×4.6 mm,3μm),the mobile phase was 0.05%sodium heptanesulfonate solution-acetonitrile(20∶1,V/V),the flow rate was 0.8 mL/min,the detection wavelength was 195 nm,the column temperature was 35℃,and the injection volume was 10μL.The change rules of contents of fructosazine and deoxyfructosazine at different temperatures(50,60,70,80℃)and relative humidity(RH,60%,75%,92%)were investigated.Results The linear ranges of fructosazine and deoxyfructosazine were 0.18-9.23μg/mL and 0.98-49.26μg/mL(r>0.9997)respectively.The limits of quantitation of fructosazine and deoxyfructosazine were 0.92 ng and 0.99 ng respectively,and their limits of detection were 0.37 ng and 0.33 ng respectively.The RSDs of precision,stability and repeatability tests were all lower than 2.0%.The average recovery rates of fructosazine and deoxyfructosazine were 98.77%and 99.43%with RSDs of 0.77%and 0.27%respectively(n=9).The content of the above two impurities was significantly positively correlated with the temperature and RH,and the change rule of deoxyfructosazine content versus time was fitted to zero order kinetics.The highest content of fructosazine and deoxyfructosazine at 80℃was 1.5 times and 3.7 times higher than that before heating respectively,and the highest content of the above two impurities at 40℃and 92%RH was 10 times and 1.6 times higher than that at 60%RH respectively.Conclusion The established method is simple,accurate,precise,stable and repeatable,which can be used for the determination of pyrazine impurities in Glucosamine Hydrochloride Tablets.High-temperature and high-humidity are important factors affecting the content of fructosazine and deoxyfructosazine in the formulation respectively.

关 键 词：盐酸氨基葡萄糖片 吡嗪类杂质 脱氧果糖嗪 果糖嗪 高效液相色谱法 影响因素 含量测定 温度 湿度 

分 类 号：R917[医药卫生—药物分析学]