title: Analysis of rocuronium in human plasma by liquid chromatography-tandem mass spectrometry with application in clinical pharmacokinetics.
abstract: 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 6h 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.
authors.affiliation: Departamento de Princípios Ativos Naturais e Toxicologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Câmpus de Araraquara, Rodovia Araraquara-Jaú km 01, ZIP 14801-902 Araraquara, SP, Brazil. Electronic address: nmoraes@fcfar.unesp.br.
authors.forename: Natália Valadares
authors.initials: NV
authors.lastname: de Moraes
authors.affiliation: Departamento de Biomecânica, Medicina e Reabilitação do Sistema Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, ZIP 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Gabriela Rocha
authors.initials: GR
authors.lastname: Lauretti
authors.affiliation: Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, ZIP 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Gabriela Campos de Oliveira
authors.initials: GC
authors.lastname: Filgueira
authors.affiliation: Departamento de Biomecânica, Medicina e Reabilitação do Sistema Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, ZIP 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Bruno Carvalho Portes
authors.initials: BC
authors.lastname: Lopes
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, ZIP 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
mesh_terms: D000328:Adult; D000732:Androstanols / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008875:Middle Aged; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D000077123:Rocuronium; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium
keywords: Human plasma; LC–MS/MS; Pharmacokinetics; Rocuronium