高效液相色谱法测定膦甲酸钠有关物质  

Determination of Related Substances in Foscarnet Sodium by HPLC

作　　者：陈明 王姗姗 乔戈 李苗 CHEN Ming;WANG Shanshan;QIAO Ge;LI Miao(Wuhan Institute For Drug and Medical Device Control,NMPA Key Laboratory for Quality Research and Control of Drug Products,Wuhan 430073,China)

机构地区：[1]武汉药品医疗器械检验所,国家药品监督管理局药物制剂质量研究与控制重点实验室,武汉430073

出　　处：《医药导报》2023年第12期1830-1834,共5页Herald of Medicine

基　　金：湖北省药品监督管理局药品安全监管科研项目(20220127)。

摘　　要：目的建立高效液相色谱(HPLC)法测定膦甲酸钠有关物质。方法采用CAPCELL PAK C 18柱(250 mm×4.6 mm,5μm),以混合溶液[取无水硫酸钠1.42 g,加冰醋酸3 mL与0.1 mol·L^(-1)焦磷酸钠溶液6 mL,加水1000 mL使溶解,作为溶液A;取无水硫酸钠1.42 g,加无水醋酸钠4.2 g与0.1 mol·L^(-1)焦磷酸钠溶液6 mL,加水1000 mL使溶解,作为溶液B;取溶液A-溶液B(70:30)混合溶液(pH值约为4.4)1000 mL,加四己基硫酸氢铵0.25 g,振摇使溶解,加甲醇100 mL,摇匀]为流动相,流速为1.0 mL·min^(-1),柱温为35℃,检测波长为230 nm,进样量为50μL。结果膦甲酸钠峰、杂质Ⅰ峰、杂质Ⅱ峰及其他单个杂质峰均能有效分离,膦甲酸钠的线性范围为5~248μg·mL-1(r=0.9999),杂质Ⅱ的线性范围为1.6~9.1μg·mL-1(r=0.9999);膦甲酸钠与杂质Ⅱ的检出限分别为23和62 ng(S/N=3);采用加样回收法,杂质Ⅰ平均回收率为100.8%,RSD=2.0%(n=6);杂质Ⅱ平均回收率为98.6%,RSD=2.7%(n=12)。结论该方法操作简便,结果准确,可用于膦甲酸钠有关物质检查。Objective To establish a method for the determination of related substances in foscarnet sodium by HPLC.Methods The chromatography separation was performed on a CAPCELL PAK C 18 chromatography column(250 mm×4.6 mm,5μm)with mobile phase of a mixture of solution[Solution A:dissolve 3.2 g of sodium sulfate decahydrate in water,add 3 mL of glacial acetic acid and 6 mL of 0.1 mol·L^(-1)sodium pyrophosphate,dilute with water to 1000 mL.Solution B:dissolve 3.2 g of sodium sulfate decahydrate in water,add 6.8 g of sodium acetate and 6 mL of 0.1 mol·L^(-1)sodium pyrophosphate,dilute with water to 1000mL.Solution A and Solution B(70:30)(the pH of this mixture is about 4.4).To 1000 mL of this solution add 0.25 g of tetrahexylammonium hydrogen sulfate and 100 mL of methanol]at a flow rate of 1.0 mL·min^(-1).The column temperature was 35℃.The detection wavelength was 230 nm and the injection volume was 50μL.Results Under the chromatography conditions,the peaks of foscarnet sodium,impurityⅠ,impurityⅡand other individual impurities were separated effectively.The foscarnet sodium and impurityⅡshowed good liner relationships(r=0.9999)in the range of 5-248μg·mL-1 and 1.6-9.1μg·mL-1,respectively.The limits of detection(LODs)of foscarnet sodium and impurityⅡwere 23 ng and 62 ng respectively.The average recovery of impurityⅠwas 100.8%,RSD=2.0%(n=6).The average recovery of impurityⅡwas 98.6%,RSD=2.7%(n=12).Conclusion The method is simple,sensitive and accurate.It is suitable for the determination of related substances in foscarnet sodium.

关 键 词：膦甲酸钠 高效液相色谱法 有关物质 

分 类 号：R978.7[医药卫生—药品] R927.2[医药卫生—药学]