张勇,陈笑艳,杨汉煜,钟大放
ZHANG Yong, CHEN Xiao yan, YANG Han yu, ZHONG Da fang (Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China)

• 1:沈阳药科大学药物代谢与药物动力学实验室
• 2:沈阳药科大学药物代谢与药物动力学实验室
• 3:沈阳药科大学药物代谢与药物动力学实验室
• 4:沈阳药科大学药物代谢与药物动力学实验室 辽宁沈阳110016

摘要(Abstract)：

目的建立测定人血浆中法莫替丁含量的液相色谱 质谱 质谱联用法。方法取 0 2mL血浆样品经液 液萃取后 ,以乙腈 水 甲酸 (3 0∶70∶1 ,V∶V∶V)为流动相 ,采用ZorbaxSBC8柱分离 ,通过电喷雾离子化四极杆串联质谱 ,以选择反应监测 (SRM)方式进行检测。用于定量分析的离子反应分别为m/z 3 3 8→m/z1 88(法莫替丁 )和m/z2 40→m/z1 47(内标 ,沙丁胺醇 )。结果法莫替丁线性范围是 2 5～ 5 0 0 0ng/mL ,最低定量限为 2 5ng/mL。日内、日间精密度 (RSD)小于 8% ,准确度(RE)在± 2 %范围内。每个样品测试时间仅为 4min,应用此法每天可以测试 1 0 0多个样品。结论该法灵敏度高 ,样品处理简单 ,分析测试速度快 ,适用于临床药物动力学研究。
Objective To develop a sensitive and rapid liquid chromatography tandem mass spectrometry (LC/MS/MS) method for the determination of the content of famotidine in the human plasma. Methods From the 0 2 mL plasma, Famotidine and internal standard salbutamol were extracted with ethyl acetate, then chromatographed using the Zorbax SB C 8 column. The mobile phase consisted of acetonitrile water formic acid (30∶70∶1, V∶V∶V ). Electrospray ionization (ESI) source was applied and operated in the positive ion mode. The selected reaction monitoring (SRM) mode using the trasitions of m/z 338→ m/z 188 and m/z 240→ m/z 147 was used to quantify the famotidine and the internal standard, respectively. Results The linear calibration curve was obtained in the concentration range of 2 5～500 0 ng/mL. The limit of quantitation was 2 5 ng/mL. The inter and intra day precision (RSD) was less than 8%, and accuracy (relative error) was within ±2%. Each plasma sample was chromatographed within 4 min. More than 100 plasma samples could be assayed within each day. The method was successfully used in a pharmacokinetic study of famotidine. Conclusions The method is proved to be suitable for the clinical investigation of famotidine pharmacokinetics, which offers advantages of specificity, speed and greater sensitivity when being compared with the reported methods.

关键词(KeyWords)： 法莫替丁;液相色谱质谱质谱联用法;血浆药物浓度
famotidine; liquid chromatography tandem mass spectrometry; plasma concentration

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目 (3 993 0 1 80 ) ;; 辽宁博士起动基金资助项目 (0 0 1 0 2 9)

作者(Author): 张勇,陈笑艳,杨汉煜,钟大放
ZHANG Yong, CHEN Xiao yan, YANG Han yu, ZHONG Da fang (Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China)

参考文献(References)：

• [1]LargtryH ,GrantS,GoaK .Famotidine anupdatedreviewofitspharmacodynamicandpharmacokineticpropertiesandtherapeuticuseinpepticulcerdiseaseandotherallieddis eases[J].Drugs,1989,38(4):551-590.
• [2]WanwimolrukS,ZoestAR ,HungCT .Sensitivehigh per formanceliquidchromatographicdeterminationoffamotidineinhumanplasma[J].JChromatogrB ,1991,572:227-238.
• [3]DowlingTC ,FryeRF .Determinationoffamotidineinhu manplasmaandurinebyhigh performanceliquidchro matography[J].JChromatogrB ,1999,732:239-243.
• [4]CarlucciG ,BiordiL ,NapolitanoT ,etal.Determinationoffamotidineinplasma,urineandgastricjuicebyhigh performanceliquidchromatographyusingdisposablesolid phaseextractioncolumns[J].JPharmBiomedAnal,1988,6(5):515-519.
• [5]LingZ ,YehKC .Determinationoffamotidineinhumanplasmabyhighperformanceliquidchromatographywithcol umnswitching[J].JPharmBiomedAnal,1998,16:1051-1057.
• [6]ZhongDF .Someaspectsinestablishingstandardcurvesinbioanalyseswiththeweightedleastsquiresmethod[J].ClinJPharmAnal(inChinese),1996,16(5):343-346.