衍生化高效液相色谱-紫外检测法测定阿仑膦酸钠和电喷雾离子阱质谱法分析其衍生物  

Assay of alendronate sodium by derivatization HPLC-UV and its derivatives by ESI-IT-MS

作　　者：戴河双 陈琴华[2] 张燕[2] 胡培[2] 陈志琼[1] 

机构地区：[1]重庆医科大学药学院药物分析教研室,重庆400016 [2]湖北医药学院附属东风医院药物分析与筛选研究所,湖北十堰442008

出　　处：《中国医院药学杂志》2015年第1期61-65,共5页Chinese Journal of Hospital Pharmacy

基　　金：湖北省卫生厅青年科技人才项目(编号:QJX2012-45);湖北省教育厅科研计划项目(编号:D20132106)

摘　　要：目的：以9-氯甲酸芴甲酯（FMOC-Cl）为柱前衍生化试剂,采用电喷雾离子阱质谱（ESI-IT-MS）技术对其衍生化物进行定性鉴别及高效液相色谱-紫外检测法测定阿仑膦酸钠片的含量。方法：阿仑膦酸钠与FMOC-Cl衍生化反应后,采用LinkSil C18色谱柱（5.0μm,250 mm×4.6 mm）,乙腈-甲醇-0.4%乙二胺四乙酸（用氢氧化钠调p H 7.16）（25∶5∶70）为流动相,测定阿仑膦酸钠的含量,并用ESI-MS获得质谱图对其衍生化产物的主要碎片进行分析。结果：在负离子模式下,阿仑膦酸钠的衍生化产物主要碎片离子为m/z 470、426、408、366、344和326。阿仑膦酸钠质量浓度在1-40 mg·L^-1范围内线性关系良好,平均回收率为101.2%,最低检测限为0.2 mg·L^-1。结论：该HPLC-UV柱前衍生法样品处理简单,测定灵敏,准确度高,可以用来测定阿仑膦酸钠片剂含量。ESI-IT-MS分析为进一步对阿仑膦酸钠的体内代谢过程与结构修饰研究提供了理论指导和实验依据。OBJECTIVE To perform qualitative identification of alendronate sodium derivatives by using ESI-IT-MS and determine the content of 9-Fluorenylmethyl chloroformate by HPLC-UV, with 9-fluorenylmethyl chloroformate （FMOC-Cl） with as the pre-column derivatization reagent.METHODS After alendronate sodium was derivatized with FMOC-Cl, content of alendronate sodium was determined on a Link Sil C18 column （5.0μm, 250 mm×4.6 mm）, with of acetonitrile-methanol-0.4%EDTA （pH value was adjusted to 7.16 by using sodium hydroxide） （25：5：70） as the mobile phase.MS was obtained by using ESI-MS to analyze the main fragments of its derivatives. RESULTS The main fragment ions of m/z 470, 426, 408, 366, 344 and 326 were found in negative mode in derivatives of alendronate sodium.Alendronate sodium had good linearity in the range of 0.2-40 mg·L^-1, its average recovery was 101.2%, limit of detection was 0.2 mg·L^-1. CONCLUSION This HPLC-UV pre-column derivization sample can be easily processed, sensitively determined with high accuracy, and can be used to determine the content of alendronate sodium. ESI-IT-MS provides theoretic guidance and experimental basis for further analyze metabolism and structural modification of alendronate sodium.

关 键 词：阿仑膦酸钠 9-氯甲酸芴甲酯 衍生 高效液相色谱 质谱 

分 类 号：R917[医药卫生—药物分析学]