用LC-MS法测定人血浆中顺式阿曲库铵的浓度

Cisatracurium assay in human plasma by LC-MS

目的建立高效液相色谱串联质谱方法(LC-MS)测定人血浆中顺式阿曲库铵的浓度,并应用于临床治疗药物监测。方法采用盐酸普罗帕酮同位素内标,样品经2%甲酸水和含内标的乙腈溶液沉淀蛋白处理。HPLC色谱柱为Agilent SB-C18,柱温35℃,流速0.3 ml/min,流动相为0.1%甲酸水和0.1%甲酸乙腈溶液,梯度洗脱。质谱检测方式为ESI正离子模式,MRM扫描,监测阿曲库铵m/z 464.6~358.4,盐酸普罗帕酮(内标)m/z 342.2~116.2。结果人血浆中顺式阿曲库铵在该条件下分离良好,在2~500 ng/ml浓度范围内线性关系良好(r=0.996 5),定量下限为2 ng/ml。方法日内精密度RSD<16.0%;日间精密度RSD<6.0%。平均回收率为97.63%~111.93%;血浆样品室温放置4 h,-80℃放置14 d,处理后室温放置24 h,稳定性良好。结论本方法简便、准确、快速、稳定,适用于顺式阿曲库铵的血药浓度测定。

Objective To establish a LC-MS method of cisatracurium assay in human plasma for clinical therapeutic drug monitoring. Method Propafenone Hydrochloride was used as the internal standard. The plasma samples were treated with2% formic acid aqueous solution and acetonitrile containing the internal standard to precipitate protein. Agilent SB-C18 column was used for gradient elution with the mobile phase of 0.1% formic acid-water and 0.1% formic acid-acetonitrile solution at 35 ℃ and0.3 ml/min flow rate. The degradation products of cisatracurium m/z 464.6-358.4 and propafenone hydrochloride m/z 342.2-116.2 were identified by ESI positive-ion detection. Results There was a linear rage of cisatracurium in 2-500 ng/ml(r=0.996 5) with a detection limit of 2 ng/ml. The intra-day coefficients of variation(CVs) were less than 16.00%, and the inter-day CVs were less than6.00%. The mean recoveries were in the range of 97.63%-111.93%. The plasma samples were stable for 4 hours at room temperature, 14 days at-80 ℃ and 24 hours after pretreated. Conclusion This method was simple, accurate, fast and repeatable for the cisatracurium assay in human plasma.