Stable isotope dilution negative ion chemical ionization gas chromatography–mass spectrometry for the quantitative analysis of paroxetine in human plasma

✍ Scribed by Hans Jörg Leis; Werner Windischhofer; Günther Raspotnig; Günter Fauler

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 141 KB
• Volume: 36
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.194

✦ Synopsis

Abstract

A sensitive and specific method for the quantitative determination of paroxetine in human plasma is presented. After solvent extraction from plasma with hexane/ethyl acetate (1 : 1) at alkaline pH and derivatization to the pentafluorobenzyl carbamate derivative, paroxetine was measured by gas chromatography–negative ion chemical ionization mass spectrometry. The carboxylate anion at m/z 372 was obtained at high relative abundance. [^2^H~6~]‐labeled paroxetine was used as an internal standard and its rapid and facile preparation from the unlabeled compound is described. Calibration graphs were linear within a range of 0.094–12.000 ng ml^−1^ using 1 ml of plasma and 0.469–60 ng ml^−1^ using 200 µl of plasma. Intra‐day precision was 1.47% (0.375 ng ml^−1^), 3.16% (3 ng ml^−1^) and 1.37% (9 ng ml^−1^) for the low‐level method, and 3.37% (1.875 ng ml^−1^), 2.72% (15 ng ml^−1^) and 2.22% (45 ng ml^−1^) for the high‐level method. Inter‐day precision was 1.65% (0.375 ng ml^−1^), 2.13% (3 ng ml^−1^) and 1.66% (9 ng ml^−1^) for the low‐level method, and 1.10% (1.875 ng ml^−1^), 1.56% (15 ng ml^−1^) and 1.90% (45 ng ml^−1^) for the high‐level method. At the limit of quantification (0.094 ng ml^−1^), intra‐day precision was 4.30% (low‐level method) and 2.56% (high‐level method), and inter‐day precision was 3.23% (low‐level method) and 3.00% (high‐level method). The method is rugged, rapid and robust and has been applied to the batch analysis of paroxetine during pharmacokinetic profiling of the drug. Copyright © 2001 John Wiley & Sons, Ltd.