HPLC-MS/ESI 法同时测定人血浆中盐酸特拉唑嗪盐酸哌唑嗪和甲磺酸多沙唑嗪  

HPLC-MS/ESI determination of terazosin hydrochloride,prazosin hydrochloride and doxazosin mesyllate in human plasma

作　　者：马宁[1] 刘文英[1] 李焕德[2] 陈本美[3] 张毕奎[4] 

机构地区：[1]药物质量与安全预警教育部重点实验室 [2]中南大学湘雅二医院临床药学研究室,长沙410011 [3]中南大学现代分析测试中心生物分析化学研究室,长沙410009 [4]中南大学湘雅三医院药剂科,长沙410013

出　　处：《药物分析杂志》2007年第10期1548-1552,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立同时测定血浆中盐酸特拉唑嗪、盐酸哌唑嗪和甲磺酸多沙唑嗪的 HPLC-MS/ESI 方法。方法:血浆样品0.5mL,加入10 ng·mL^(-1)二盐酸氟哌噻吨内标液50 μL,经饱和碳酸钠200 μL碱化和1.25 mL 正已烷-叔丁基甲醚(1:1)萃取;以Hypersil GOLD C_(18)柱(100 mm×2.1 mm,5 μm)为固定相,20 mmol·L^(-1)醋酸铵(0.05%甲酸,pH 4.2)-乙腈-甲醇为流动相,梯度洗脱分离,流速为0.2 mL·min^(-1);采用 HPLC-MS,选择离子检测(SIM)法测定盐酸特拉唑嗪([M+H]^+,m/z 388)、盐酸哌唑嗪([M+H]^+,m/z 384)、盐酸多沙唑嗪([M+H]^+,m/z 452和内标氟哌噻吨([M+H]^+,m/z 435)的血药浓度。结果:线性范围为1～100 ng·mL^(-1),r>0.9930(n=7);萃取回收率大于83.0%;方法回收率大于97.0%;日内、日间精密度 RSD 均小于10.0%。结论:该方法灵敏、专属、快速,适用于3种药物的血药浓度监测,以及药代动力学和生物等效性的研究。Objective：To establish an analytical method for simultaneous determination of terazosin hydrochloride, prazosin hydroehloride, doxazosin mesyllate in human plasma by high -performance liquid ehromatography/electros- pray - mass spectrometry （ HPLC - MS/ESI ）. Method： Flupentixol dihydroehloride was selected as the internal standard （IS）. Samples were extracted using n-hexane/tert - butyl methyl ether （ 1 ： 1, v/v）. The separation was a- chieved on a Hypersil GOLD Cls column（ 100 mm ×2. 1 mm,5 μm ） with aqueous solution （20 mmol· L^-1 ammonium acetate,0. 05 % formic acid, pH 4.2）, aeetonitrile and methanol as mobile phase with a gradient mode, with a flow rate of 0. 2 mL · min^-1. The quantification of target compounds was using a selective ionization recording [ M＋H ]^＋ at m/z 388 for terazosin, m/z 384 for prazosin,m/z 452 for doxazosin and m/z 435 for flupentixol dihydro- chloride. Results： The correlation coefficients of the calibration curves were better than 0. 9930 （ n = 7 ）, in the range of 1 - 100 ng · mL^-1 for terazosin, prazosin and doxazosin. The average extraction recoveries for all the four analytes were above 83. 0%. The methodology recoveries were higher than 97. 0%. The intra - day and inter - day RSDs were less than 10. 0 %. Conclusion：The method is accurate, sensitive and simple for routine therapeutic drug monitoring （ TDM）, as well as for the study of the pharmaeokineties and bioequivalenee of the three drugs and has beensuccessfully applied to the bioequivalence study of terazosin hydrochloride tablets.

关 键 词：特拉唑嗪 哌唑嗪 多沙唑嗪 HPLC-MS/ESI 药代动力学 生物等效性 

分 类 号：R917[医药卫生—药物分析学]