Analysis of rocuronium in human plasma by liquid chromatography–tandem mass spectrometry with application in clinical pharmacokinetics

•A LC–MS/MS method was developed and fully validated to analyze rocuronium in plasma.•This is the most sensitive analysis for rocuronium and requires only 100 μL plasma.•The advantages of this method are greater selectivity and simple sample preparation.•Rocuronium was analyzed in plasma up to 6 h after administration of a single dose.

Rocuronium (ROC) is a neuromuscular blocking agent used in surgical procedures which is eliminated primarily by biliary excretion. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for analysis of ROC in human plasma. Separation of ROC and IS (verapamil) was performed using an endcapped C-18 column and a mixture of water:acetonitrile:trifluoracetic acid (50:50:0.1, v/v) as mobile phase. Aliquots of 100 μL of human plasma were extracted at pH 3, using dichloromethane. The lower limit of quantification of 5 ng/mL shows the high sensitivity of this method. Intra- and inter-assay precision (as relative standard deviation) was all ≤14.2% and accuracy (as relative standard error) did not exceed 10.1%. The validated method was successfully applied to quantify ROC concentrations in patients under surgical procedures up to 6 h after the administration of the 0.4–0.9 mg/kg ROC. The pharmacokinetic parameter estimations of ROC showed AUC/dose of 563 μg min/mL, total clearance of 2.5 mL/min/kg, volume of distribution at steady state of 190 mL/kg and mean residence time of 83 min.

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