Determination of RSD921 in human plasma by high-performance liquid chromatography-tandem mass spectrometry using tri-deuterated RSD921 as internal standard: application to a phase I clinical trial.
A fast, sensitive and specific method is presented for the quantification of RSD921 in human plasma by liquid chromatography coupled with tandem mass spectrometry using tri-deuterated RSD921 (3d-RSD921) as an internal standard. A single-step liquid/liquid extraction was performed with diethyl ether/hexane (80 : 20, v/v) using 0.5 ml of plasma. The plasma calibration curves were linear from 0.1 to 20 ng ml(-1) (r > 0.999). Between-run precision, based on the percent relative deviation for replicate (n = 40) quality controls, was < or =7.27% (0.5 ng ml(-1)), < or =7.39% (5.0 ng ml(-1)), and < or =5.06% (20.0 ng ml(-1)). Between-run accuracies, based on the relative error, were +/-2.59%, +/-1.23% and +/-1.64% respectively. The method was developed to evaluate the pharmacokinetic profile after 15 min of intravenous stepwise-ascending infusion dose of RSD921 in 18 healthy volunteers. A dissociation study of protonated RSD921 and 3d-RSD921 by collision-induced dissociation using in-source fragmentation and tandem mass spectrometry is also presented.
Ribeiro
W
W
Cartesius Analytical Unit, Department of Pharmacology ICB-USP, 05508-900, São Paulo, SP, Brazil.
Ifa
D R
DR
Corso
G
G
Salmon
J
J
Moraes
L A
LA
Eberlin
M N
MN
de Nucci
G
G
D000779:Anesthetics, Local / Q000097:blood* / Q000493:pharmacokinetics; D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D017321:Clinical Trials, Phase I as Topic; D003903:Deuterium; D006801:Humans; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D011758:Pyrroles / Q000097:blood* / Q000493:pharmacokinetics; D011786:Quality Control; D012015:Reference Standards; D013876:Thiophenes / Q000097:blood* / Q000493:pharmacokinetics
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D007202:Indicators and Reagents; D011758:Pyrroles; D013876:Thiophenes; C054718:PD 117302; D003903:Deuterium