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Automated LC-MS Method for the Fast Stereoselective Determination of Methadone in Plasma

  • Sandrine Souverain , Chin Eap , Jean-Luc Veuthey and Serge Rudaz
Published/Copyright: June 1, 2005
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Volume 41 Issue 12

Abstract

Methadone (MTD) is a chiral drug widely used for the treatment of opioid dependence for which a rapid analytical method for the determination of each enantiomer would be advantageous. In order to improve method sensitivity and to automate the entire analytical process, a column-switching configuration has been developed. An online extraction system coupled to a cellulose-based chiral stationary phase (CSP), namely Chiralcel OJ-R, was used and detection was performed by mass spectrometry. Fifty μl of plasma were injected into the liquid chromatography-mass spectrometry (LC-MS) system after addition of acetonitrile (ACN) containing methadone deuterated D9 (MTD-D9) (internal standard) and centrifugation. For the rapid extraction step, a large particle size support was selected. A baseline separation of MTD enantiomers was obtained in less than 12 min. Trueness and precision were evaluated with control samples at 500 ng/ml of (R,S)-methadone. Trueness values were 106.6% and 103.0% for (R)-MTD and (S)-MTD, respectively, with a coefficient of variation inferior to 2.5% for both compounds. Finally, a good concordance was found using this method for analysis of plasma samples from patients in maintenance treatment as compared to a previously described HPLC-UV method after liquid-liquid extraction.

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Published Online: 2005-06-01
Published in Print: 2003-12-04

Copyright © 2003 by Walter de Gruyter GmbH & Co. KG

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