title: Automated LC-MS method for the fast stereoselective determination of methadone in plasma.
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.
authors.affiliation: Laboratory of Analytical Pharmaceutical Chemistry, School of Pharmacy, University of Geneva, Geneva, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Souverain
authors.forename: Chin
authors.initials: C
authors.lastname: Eap
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Veuthey
authors.forename: Serge
authors.initials: S
authors.lastname: Rudaz
mesh_terms: D000701:Analgesics, Opioid / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008691:Methadone / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone