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.
Laboratoire de Pharmacocinétique Clinique, Faculté de Pharmacie, Montpellier, France.
C
C
Farenc
C
C
Enjalbal
P
P
Sanchez
F
F
Bressolle
M
M
Audran
J
J
Martinez
J L
JL
Aubagnac
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