用LC-MS/MS法测定人血浆中环泊酚与丙泊酚的浓度

Determination of ciprofol and propofol in human plasma by LC-MS/MS method

目的建立人血浆中环泊酚与丙泊酚浓度的测定方法,并应用于全麻择期手术患者血浆中药物浓度的检测。方法血浆样本经乙腈沉淀,Symmetry C_(18)(4.6 mm×150.0 mm,3.5μm)色谱柱;流动相:A相为0.01%氨水溶液(含5 mmol·L^(-1)乙酸铵),B相为乙腈;梯度洗脱;流速:0.70 mL·min^(-1);内标为D6-环泊酚。用电喷雾电源,多反应监测的负离子模式。考察该方法的专属性、标准曲线和定量下限、精密度与回收率、稳定性及基质效应。结果人血浆中环泊酚质量浓度在15~2000 ng·mL^(-1)内呈线性关系,标准曲线方程y=1.94×10^(-3)x+8.17×10^(-3);人血浆中丙泊酚质量浓度在30~4000 ng·mL^(-1)内呈线性关系,标准曲线方程y=3.29×10^(-3)x+6.90×10^(-2)。环泊酚和丙泊酚的日内和日间精密度的相对标准偏差均小于9%,绝对回收率均在90%以上,分析物的基质效应在±7%内。21例手术患者血浆中环泊酚和丙泊酚质量浓度范围分别为388.82~1135.66 ng·mL^(-1)和1015.98~2796.43 ng·mL^(-1)。结论本方法准确高效,符合生物样本分析要求,可同时测定人血浆中环泊酚和丙泊酚的浓度,适用于临床血药浓度监测和人体药代动力学研究。

Objective To establish a method for determination of ciprofol and propofol in human plasma and apply it to detect the drug concentration of general anesthesia in patients plasma undergoing elective surgery.Methods Plasma samples were precipitated with acetonitrile,and Symmetry C_(18) column(4.6 mm×150.0 mm,3.5μm)was selected and the mobile phase consisted of acetonitrile(B)and 0.01%ammonia water(containing 5 mmol·L^(-1)ammonium acetate;A)with gradient elute.The internal standard was D6-ciprofol.Electrospray power supply and negative ionization of multi-reaction monitoring were used for mass spectrum conditions.The specificity,linearity and lower limit of quantitation,precision,recovery rate,and matrix effects of the method were investigated.Results The concentration of ciprofol in human plasma was linear in the range of 15-2000 ng·mL^(-1);and the standard curve equation was y=1.94×10^(-3)x+8.17×10^(-3).The concentration of propofol in human plasma was linear in the range of 30-4000 ng·mL^(-1);and the standard curve equation was y=3.29×10^(-3) x+6.90×10-2.The relative standard deviation values of ciprofol and propofol for intra-day and inter-day precision were less than 9%,and the absolute recoveries were both above 90%.The matrix effects of the analytes were within the range of±7%.The concentrations of ciprofol and propofol in plasma samples of 21 patients were 388.82-1135.66 ng·mL^(-1)and 1015.98-2796.43 ng·mL^(-1),respectively.Conclusion The method established conformed to the standards for analyzing biological samples is convenient with high accuracy,and can simultaneously determine the concentrations of ciprofol and propofol in human plasma,which is suitable for clinical blood concentration monitoring and human pharmacokinetic study.