LC-MS/MS法测定全膝关节置换术患者血浆中罗哌卡因的浓度及局部给药的安全性

Determination of ropivacaine in plasma of human administrated total knee arthroplasty by LC-MS /MS and safety study of local drug delivery

目的 建立LC-MS/MS法测定全膝关节置换术患者血浆中罗哌卡因的浓度并研究局部给药方案的安全性.方法用Zorbax SB-C18柱,以甲醇-20 mmol·L-1甲酸铵溶液（70∶30）为流动相,流速为0.3 mL·min-1,苯海拉明为内标,血浆样品经乙腈沉淀蛋白质后进样,用正离子模式,多反应监测扫描.结果罗哌卡因在99.2~4980.0 ng·mL-1内线性关系良好（r=0.999 0）,日内、日间RSD均〈10%,绝对回收率在90.5%~96.9%.股神经阻滞给予罗哌卡因100 mg/20 mL后,最高血药浓度为1220 ng·mL-1（n=17）.术中关节腔注射罗哌卡因100 mg/20 mL后,最高浓度为2250 ng·mL-1（n=10）.结论本方法操作简便,进样量小,灵敏度高,特异性强,可用于临床罗哌卡因血药浓度的监测.对于全膝关节置换术,关节腔注射罗哌卡因100 mg/20 mL安全有效.

Objective To determinate a method for the determination of ropivacaine in human plasma of patients who underwent total knee arthroplasty and to study the safety and the appropriate dose of the ropivacaine in the control of post-knee arthroscopy pain. Methods The system used a Zorbax SB-C18 analytical column. The isocratic mobile phase consisted of methanol and 20 treated by adding diphenhydramine as an intimal standard, and used ACN to precipitate proteins out of plasma sample and then injected the supernatant 3 μL The relative standard deviation of inner-day and inter-day was less than 10%, the recovery rate of extraction ranged from 90.5%-96.9%. Seventeen patients received a single-dose of ropivacaine 100 mg/20 mL in a single-injection femoral nerve block at the beginning of surgery, the maximum concentration of Ten patients received aintra-articular injection of ropivacaine 100 mg/20 mL during the surgery, the maximum concentration of ropivacaine in the plasma was determination of ropivacaine is simple, specific, sensitive and proved to be suitable for the analysis of plasma samples collected during a clinical trial. Single dose of 100 mg ropivacaine via intra-articular injection was shown a safe way.