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Abstract：
Background Ropivacaine is a widely used local anaesthetic drug, highly bound to plasma proteins with a free plasma fraction of about 5%. Therefore, the monitoring of free drug concentration is most relevant to perform pharmacokinetic studies and to understand the drug pharmacokinetic/pharmacodynamic (PK/PD) relationship. Methods A high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using reverse-phase LC and electrospray ionisation mass spectrometry with multiple reaction monitoring (MRM) is described for the quantitation of both free and total ropivacaine in human plasma. Ropivacaine-d7 was used as an internal standard (IS). Results The method was validated in the range 0.5-3000 ng/mL, with five levels of QC samples and according to the European Medicine Agency and Food and Drug Administration guidelines. The performance of the method was excellent with a precision in the range 6.2%-14.7%, an accuracy between 93.6% and 113.7% and a coefficient of variation (CV) of the IS-normalised matrix factor below 15%. This suitability of the method for the quantification of free and total ropivacaine in clinical samples was demonstrated with the analysis of samples from patients undergoing knee arthroplasty and receiving a local ropivacaine infiltration. Conclusions A method was developed and validated for the quantification of free and total ropivacaine in human plasma and was shown suitable for the analysis of clinical samples.
摘要：
背景罗哌卡因是一种广泛使用的局部麻醉药物,与血浆蛋白高度结合，游离血浆比例约为5％。因此,游离药物浓度的监测与进行药代动力学研究和了解药物药代动力学/药效学(PK/PD)关系最为相关.方法描述了一种使用反相LC和具有多反应监测（MRM）的电喷雾电离质谱（LC-MS/MS）的高灵敏度液相色谱-串联质谱（LC-MS/MS）方法，用于定量人血浆中的游离和总罗哌卡因。罗哌卡因d7用作内标（IS）。结果该方法在0.5-3000ng/mL范围内得到验证，与五个级别的质量控制样品，并根据欧洲药品管理局和食品和药物管理局的指导方针。该方法性能优异，精密度在6.2%-14.7%范围内，准确率在93.6%和113.7%之间，IS归一化矩阵因子的变异系数(CV)低于15%。通过分析接受膝关节置换术并接受局部罗哌卡因浸润的患者的样品，证明了该方法对临床样品中游离和总罗哌卡因定量的适用性。结论开发并验证了一种定量人血浆中游离和总罗哌卡因的方法，该方法适用于临床样品的分析。
