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Automated LC-MS method for the fast stereoselective determination of methadone in plasma

Souverain, Sandrine
Eap, Chin
Published in Clinical chemistry and laboratory medicine. 2003, vol. 41, no. 12, p. 1615-1621
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 microl 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.
Keywords Methadone enantiomersChiralcel OJ-RPlasma samplesLiquid chromatography-mass spectrometry: LC-MSColumn-switching
PMID: 14708886
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SOUVERAIN, Sandrine et al. Automated LC-MS method for the fast stereoselective determination of methadone in plasma. In: Clinical chemistry and laboratory medicine, 2003, vol. 41, n° 12, p. 1615-1621. doi: 10.1515/CCLM.2003.245 https://archive-ouverte.unige.ch/unige:82071

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Deposited on : 2016-03-22

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