LC-MSMS法测定人血浆及尿液中缬沙坦的浓度及其药动学研究-中国药房.PDFVIP

LC-MS/MS 法测定人血浆及尿液中缬沙坦的浓度及其药动学研究 ＊ # 冯仕银 ，雍小兰 ，黄 娟，杜晓琳，李 楠，王蓝天（成都军区总医院临床药学科，成都 610083） 中图分类号 R969.1 文献标志码 A 文章编号 1001-0408（2016）05-0619-03 DOI 10.6039/j.issn. 1001-0408.2016.05.13 摘 要 目的：建立测定人血浆及尿液中缬沙坦浓度的方法。方法：血浆样品经酸化后用乙醚提取浓度后进行分析；尿液样品直 接稀释进样，均采用液相色谱- 串联质谱（LC-MS/MS ）法测定，色谱柱为Aglient ZORBAX SB-C18，流动相为0.1％甲酸-乙腈（梯度 洗脱），流速0.2ml/min 。电喷雾离子源（ESI ），正离子多反应监测模式测定，缬沙坦定量分析的离子对为m/z 436.4→253.2，定性分 析离子对为m/z 436.4→291.3；内标氯沙坦定量分析的离子对为m/z 423.4→207.1，定性分析离子对为m/z 423.4→180.2。结果：血 浆和尿液中缬沙坦的线性范围分别为4～5000ng/ml （r ＝0.9985）、20～50000ng/ml （r ＝0.9988）；最低定量限分别为4、20ng/ml ； 血浆萃取回收率为61.21％～70.30％；内标归一化基质效应因子的RSD 分别为3.20％、11.21％；日内和日间RSD 均≤8.34％。结 论：所用方法快速、灵敏度高，适用于人血浆及尿液中缬沙坦的浓度测定及药动学研究。 关键词 液相色谱- 串联质谱法；缬沙坦；血药浓度；尿液浓度；药动学 Determination of Valsartan in Human Plasma and Urine by LC-MS/MS and Its Pharmacokinetic Study FENG Shiyin ，YONG Xiaolan ，HUANG Juan ，DU Xiaolin ，LI Nan ，WANG Lantian （Dept. of Clinical Pharmacy ， General Hospital of Chengdu Military Command ，Chengdu 610083，China ） ABSTRACT OBJECTIVE ：To develop a method for the determination of valsartan concentration in human plasma and urine. METHODS ：Plasma sample were acidified and extracted with diethyl ether for analysis ，and urine sample was diluted directly for analysis. The samples were all determined by LC-MS/MS ，and the separation was performed on a Aglient ZORBAX SB-C18 column with mobile phase consisted of acetonitrile and 0.1％formic acid （gradient elution ）at flow rate of 0.2 ml/min. Ion transition was determined ESI ion source under multiple ion reaction monitoring with quantitative pair m/z 436.4→253.2 and qualitative ion pair m/z 436.4→291.3 for valsartan ，and quantitative pair m/z 423.4→207.1 and m/z 423.4→180.2 for internal standard losartan. RE- SULTS ：The linear range of valsartan were 4-5 000ng/ml in plasma and 20-50 000ng/ml in urine ；the limit of quantification were 4 n