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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