固相萃取-高效液相色谱法同时测定人血浆中地西泮、咪达唑仑及其代谢产物的浓度和临床应用  

Simultaneous determination of diazepam,midazolam and metabolites in human plasma by HPLC with solid phase extraction

作　　者：郭志磊[1] 范捷[1] 于洋[1] 

机构地区：[1]江汉大学附属医院药剂科,湖北武汉430015

出　　处：《中国医院药学杂志》2016年第10期825-829,共5页Chinese Journal of Hospital Pharmacy

摘　　要：目的:建立同时测定人血浆中地西泮、奥沙西泮、咪达唑仑和1′-羟基咪哒唑仑浓度的固相萃取-高效液相测定方法,并将其应用于临床中地西泮、咪达唑仑及其代谢产物血药浓度的测定。方法:以卡马西平为内标,血浆样品经Cleanert C18固相萃取柱净化处理。色谱柱为WondaSil C18柱(150 mm×4.6 mm,5μm),流动相为乙腈-水=55∶45,柱温:30℃,流速:1.2mL·min-1,检测波长:308 nm,进样量:30μL。结果:地西泮、奥沙西泮、咪达唑仑和1’-羟基咪哒唑仑标准曲线范围分别为0.5~20,0.2~10,0.5~40,0.5~20 mg·L^(-1),最低定量限分别为0.5,0.2,0.5,0.5 mg·L^(-1),方法回收率分别为88.32%~93.77%,86.14%~91.80%,87.55%~92.53%,88.69%~92.30%,日内、日间精密度均小于7%。结论:该方法简便快速,灵敏准确,测定结果可靠,适用于地西泮、咪达唑仑及其代谢产物血药浓度的检测。OBJECTIVE To establish a new solid phase extraction（SPE）-HPLC method for simultaneous determination of diazepam,oxazepam,midazolam and 1′-hydroxymidazolam in human plasma for clinically therapeutic drug monitoring.METHODS Plasma samples were cleaned up by SPE.Carbamazepine was used as internal standard.Analyses were carried out on a WondaSil C18column（150 mm×4.6 mm,5μm）with a mobile phase composed of acetonitrile-water（55∶45）at a flow rate of1.2 mL·min-1.Detection wavelength was 308 nm,and column temperature was 30 ℃.RESULTS Calibration curves were linear within range of 0.5-20 mg·L^-1 for diazepam,0.2-10 mg·L^-1 for oxazepam,0.5-40 mg·L^-1 for midazolam and 0.5-20mg·L^-1 for 1′-hydroxymidazolam.Lower limits of quantification were 0.5,0.2,0.5,0.5 mg·L^-1,and method recoveries were 88.32%-93.77%,86.14%-91.80%,87.55%-92.53% and 88.69%-92.30%,respectively.RSDs of interday and intraday were both less than 7%.CONCLUSION This method is simple,rapid,sensitive,accurate and stable,and suitable for clinical study on pharmacokinetics of diazepam and midazolam,and drug monitoring.

关 键 词：固相萃取法 高效液相色谱法 地西泮 奥沙西泮 咪达唑仑 1’-羟基咪哒唑仑 血药浓度 

分 类 号：R917[医药卫生—药物分析学]