反相高效液相梯度洗脱法测定人血浆中丙泊酚浓度

摘要

Objective To establish an HPLC method for the determination of propofol in human plasma and to provide basis for ensu-ring the effectiveness and safety of clinical medication.Methods With carbamazepine as the internal standard,the separation was per-formed with a Hanbon Science&.Technology C18 (4.6 mm ×250 mm,5μm) column using a binary gradient elution of a mixed solution of acetonitrile and methanol(acetonitrile∶methanol=80∶20,V/V)-1%trifluoroacetic acid water (pH 4.0) ,0~7 min(50∶50,V/V),7~9 min(50∶50~70∶30,V/V),9~22 min(70∶30,V/V);flow velocity was 1.0 mL· min-1 and the wavelength of detector was set at 272 nm,injected sample volume was 20μL,and the column temperature was set at 40℃.Results The linear range of propofol was 0.098~25 mg· L-1 ( r=0.999 8) with the lower limit of quantization of 0.098 mg· L-1 .The methodological recoveries of three levels of con-centration of high (12.50 mg· L-1 ),medium (1.56 mg· L-1 ) and low (0.19 mg· L-1 )were between 85%and 115%.The RSD was less than 10%.Intraday and interday variations were both less than 10%.Conclusions The method provides a sensitive,accurate, precise and reliable analytical procedure for the therapeutic drug monitoring of propofol in clinic and phamacokinetic studies.%目的：建立高效液相色谱法测定人血浆中丙泊酚血药浓度的方法，为保证临床用药的有效性和安全性提供依据。方法以卡马西平为内标，色谱柱为Hanbon Science ＆．Technology C18（4．6 mm ×250 mm，5μm），流动相以乙腈／甲醇混合液（乙腈—甲醇按80∶20（V／V）的比例配制，作为有机相）—水（水相加1％的三氟乙酸调pH值到4）进行二元梯度洗脱，0～7 min （50∶50，V／V），7～9 min（50∶50～70∶30，V／V），9～22 min（70∶30，V／V）；流流速为1．0 mL· min－1，检测波长为274 nm，进样量为20μL，柱温为40℃。结果丙泊酚的血药浓度在0．098～25 mg· L－1内线性良好（r＝0．9998），定量限为0．098 mg· L－1；高（12．50 mg· L－1）、中（1．56 mg· L－1）、低（0．19 mg· L－1）3个浓度的平均方法回收率均在85％～115％之间，相对标准偏差（ RSD）均＜10％；日内、日间RSD均＜10％。结论该方法灵敏、准确、简单，可用于丙泊酚的血药浓度监测和临床药动学研究。