摘要
目的:建立有效测定人血浆中丙戊酸钠浓度的高效液相色谱-质谱连用(HPLC-MS/MS)的方法。方法:血浆样本经乙腈沉淀蛋白后,以替米沙坦为内标,采用Agilent ZORBAX300SB-C18柱(2.1 mm×150 mm, 5μm)色谱柱,乙腈-20 mmol·L-1乙酸胺(55∶45)为流动相,流速0.25 mL·min -1,以液相色谱分离,电喷雾离子化串联质谱进行检测,采用多反应监测(MRM)测定丙戊酸钠(m/z 143.0→m/z 143.0)和内标替米沙坦(m/z 513.5→m/z 469.4)的浓度。结果:校准曲线线性浓度范围从0.2~100μg·mL-1,最低定量限为0.2μg·mL-1。3个不同浓度(低、中、高)丙戊酸钠提取回收率分别为90.46%,93.18%,95.31%。日内和日间精密度均小于10%和8%。结论:此法简单灵敏,重现性好。已成功应用于丙戊酸钠片在中国健康志愿者的药动学研究。
OBJECTIVE To establish a high performance liquid chromatography-mass spectrometry(HPLC-MS/MS)method for the determination of sodium valproate in human plasma.METHODS Plasma samples were precipitated with acetonitrile and analyzed with an Agilent ZORBAX300 SB-C18(2.1 mm×150 mm,5μm)column using acetonitrile-20 mmol·L-1 amine acetate(55∶45)as the mobile phase at a flow rate of 0.25 mL min-1.The proteins were separated by liquid chromatography and detected by electrospray ionization tandem mass spectrometry.The concentrations of sodium valproate(m/z 143.0→m/z 143.0)and internal standard telmisartan(m/z 513.5→m/z 469.4)were determined by multiple reaction monitoring(MRM).RESULTS The linear concentration range of the calibration curve was from 0.2 to 100μg·mL-1,and the lowest limit of quantitation was 0.2μg·mL-1.The recovery rates of sodium valproate extracted at three different concentrations(low,medium and high)were 90.46%,93.18%and 95.31%,respectively.The intra-and inter-day precisions were less than 10%and 8%.CONCLUSION The method is simple,sensitive and reproducible.It has been successfully applied to the pharmacokinetic study of valproate sodium tablets in Chinese healthy volunteers.
作者
范玥
李虎群
程龙
FAN Yue;LI Hu-qun;CHENG Long(Department of Clinical Laboratory,The Central Hospital of Wuhan,Tongji Medical College,Huazhong University of Science and Technology,Hubei Wuhan 430014,China;Department of Pharmacy,The Central Hospital of Wuhan,Tongji Medical College,Huazhong University of Science and Technology,Hubei Wuhan 430014,China)
出处
《中国医院药学杂志》
CAS
北大核心
2019年第12期1244-1247,共4页
Chinese Journal of Hospital Pharmacy
基金
国家青年科学基金项目(项目批准号:81803637)
