HPLC法测定帕瑞昔布钠潜在基因毒性杂质  

Determination of Potential Genotoxic Impurities in Parecoxib Sodium by HPLC

作　　者：李士桥 王珺 周勇 杜明松 蔡雪燕 LI Shiqiao;WANG Jun;ZHOU Yong;DU Mingsong;CAI Xueyan(Bengbu BBCA Medical Science Co.,Ltd.,Bengbu Anhui 233010,China;Bengbu BBCA Tushan Pharmaceutical Co.,Ltd.,Bengbu Anhui 233010,China;COFCO Biotechnology Co.,Ltd.,Bengbu Anhui 233010,China)

机构地区：[1]蚌埠丰原医药科技发展有限公司,安徽蚌埠233010 [2]蚌埠丰原涂山制药有限公司,安徽蚌埠233010 [3]中粮生物科技股份有限公司,安徽蚌埠233010

出　　处：《当代化工》2025年第1期241-247,共7页Contemporary Chemical Industry

摘　　要：建立了HPLC法同时测定帕瑞昔布钠苯磺酸乙酯和苯磺酸异丙酯类潜在基因毒性杂质的分析方法,采用Agilent Plus C18色谱柱(250 mm×4.6 mm,5μm),检测波长为240 nm,流速为1.0 mL·min^(-1),柱温为45℃,进样量为20μL,流动相为乙腈:0.01 mol·L^(-1)磷酸二氢钠溶液(用氢氧化钠调节pH至7.5)(50∶50,v/v)。结果表明:该法系统适用性和专属性良好,2个杂质(杂质M和N)分离度达9.65。杂质M的检测限(LOD)和定量限(LOQ)分别为0.29 ng和0.73 ng;杂质N的LOD和LOQ分别为0.3 ng和1.0 ng。杂质M在0.036575~0.292600μg·mL^(-1)和杂质N在0.0502~0.2906μg·mL^(-1)均呈良好线性关系。精密度和溶液稳定性均符合要求。杂质M和N平均加样回收率(n=9)分别为96.5%和89.6%,RSD分别为4.1%和4.9%,准确度符合要求。改变柱温、流速、流动相比例、检测波长等参数,对杂质M和N保留时间和分离度没有明显影响,表明该法的耐用性良好。该法操作简单、准确、灵敏度高,可有效控制帕瑞昔布钠苯磺酸酯类潜在基因毒性杂质。A method was established for determination of potential genotoxic impurities such as ethyl and isopropyl esters of benzenesulfonic acid in parecoxib sodium by HPLC.The analysis was carried out by an Agilent Plus C18 column(250 mm×4.6mm,5μm),detection wavelength was 240 nm,flow rate was 1.0 mL·min^(-1),the column temperature was 45℃,injection volume was 20μL,the mobile phase composed of acetonitrile and 0.01 mol·L^(-1) sodium dihydrogen phosphate solution(adjusting pH to 7.5 with sodium hydroxide)(50∶50,v/v)was used to determine.The results showed,the method had good system applicability and specificity,with a resolution of 9.65 for the two impurities(impurity M and N).LOD and LOQ of impurity M were 0.29 ng and 0.73 ng,respectively;LOD and LOQ of impurities N were 0.3 ng and 1.0 ng,respectively.It was linear for impurity M in the range of 0.036575~0.292600μg·mL^(-1),and it was linear for impurities N in the range of 0.0502~0.2906μg·mL^(-1).Precision and solution stability met the requirements.The average recoveries(n=9)of sample addition for impurity M and N were 96.5%,and 89.6%with RSDs of 4.1% and 4.9%,respectively,and accuracy met the requirements.Changing parameters such as column temperature,flow rate,mobile phase ratio,and detection wavelength did not significantly affect the retention time and resolution of impurities M and N,indicating good robustness of this method.This analytical method is simple,accurate and highly sensitive,and can effectively control potential genotoxic impurities such as benzenesulfonate in parecoxib sodium.

关 键 词：帕瑞昔布钠 高效液相色谱法 基因毒性杂质 

分 类 号：TQ460.72[医药卫生—药物分析学]