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

✍ Scribed by Wellington Ribeiro; Demian R Ifa; Gaetano Corso; John Salmon; Leonardo A. Moraes; Marcos N. Eberlin; Gilberto de Nucci

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 151 KB
• Volume: 36
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.218

✦ Synopsis

Abstract

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.