Quantitative determination of rocuronium in human plasma by liquid chromatography-electrospray ionization mass spectrometry.
Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) was used for the quantification of the neuromuscular blocking agent rocuronium in human plasma. Verapamil was used as internal standard. The samples were subjected to a dichloromethane liquid-liquid extraction after ion pairing of the positively charged ammonium compound with iodide prior to LC-MS. Optimized conditions involved separation on a Symmetry Shield RP-18 column (50 x 2.1 mm, 3.5 microm) using a 15-min gradient from 10 to 90% acetonitrile in water containing 0.1% trifluoroacetic acid at 250 microl/min. Linear detector responses for standards were observed from 25 to 2,000 ng/ml. The extraction recovery averaged 59% for rocuronium and 83% for the internal standard. The limit of quantification (LOQ), using 500 microl of plasma, was 25 ng/ml. Precision ranged from 1.3 to 19% (LOQ), and accuracy was between 92 and 112%. In plasma samples, at 20 and 4 degrees C, rocuronium was stable at physiological pH for 4 h; frozen at -30 degrees C it was stable for at least 75 days. The method was found suitable for the analysis of samples collected during pharmacokinetic investigations in humans.
Farenc
C
C
Laboratoire de Pharmacocinétique Clinique, Faculté de Pharmacie, Montpellier, France.
Enjalbal
C
C
Sanchez
P
P
Bressolle
F
F
Audran
M
M
Martinez
J
J
Aubagnac
J L
JL
D000732:Androstanols / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D009466:Neuromuscular Blocking Agents / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D000077123:Rocuronium; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014700:Verapamil / Q000097:blood
D000732:Androstanols; D009466:Neuromuscular Blocking Agents; D014700:Verapamil; D000077123:Rocuronium