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 ≤7.27% (0.5 ng ml-1), ≤7.39% (5.0 ng ml-1), and ≤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. Copyright © 2001 John Wiley & Sons, Ltd.