Chiral On-Line Solid Phase Extraction Coupled to Liquid Chromatography-Tandem Mass Spectrometry Assay for Quantification of (R) and (S) Enantiomers of Methadone and Its Main Metabolite in Plasma.

International audienceThe authors aimed at developing a liquid chromatography tandem mass spectrometry (LC-MS/MS) method with online extraction to determine (R)- and (S)- methadone enantiomers and its main metabolite 2-ethylidine-1,5-dimethyl-3,3 diphenylpyrrolidine (EDDP) in plasma. The analysis combined straightforward sample preparation, consisting of protein precipitation with acetonitrile, and an online enrichment by a flush/back-flush cycle before the second dimension chromatography. Using D3-deuterated internal standards allows overcoming significant relative matrix effect. Our method was linear up to 2000 ng/mL. This simple sample preparation provides sensitive (the limit of quantitation is 25 ng/mL for (R,S)-methadone and EDDP and 12.5 ng/mL for (R)- and (S)- methadone), accurate and precise (the intra-day and inter-day imprecision and inaccuracy are lower than 15%) quantification of the plasma concentration of these drugs. We have developed a reliable LC-MS/MS method for both routine therapeutic drug monitoring and pharmacokinetics studies and for toxicology analysis in the setting of methadone treatment or intoxication

Use of Psychotropic Drug Urine Test Strips in Opiate Maintenance Therapy: A Clinical Assessment of Its Advantages.

International audienceBACKGROUND: Methadone and buprenorphine are the 2 opiate maintenance treatments (OMTs) available in France. According to good clinical practices, a full clinical and biological assessment is required before deciding to initiate or renew an OMT. For methadone, this assessment includes psychoactive drug consumption investigation through an initial interview completed by a systematic urine test mandatory before starting methadone treatment. In case of buprenorphine prescription, the situation is less clear and the urine test was not systematically performed. This work aims at evaluating changes in the therapeutic strategy brought by the systematic use of urine strips for detecting drug consumptions. METHODS: During 1 month, for each case of OMT renewal, physicians belonging to the 3 types of prescribing structures in France (general medicine, specialized centers for drug addict patients, and specialized centers for drug addict patients in prison) had to complete a specific questionnaire about prescription renewal. This questionnaire contained 2 parts. The first part was completed by the physicians before the urine test strip realization. The second part was completed by the same physicians at the end of the consultation, after obtaining the results from the urine test strip. A change between parts 1 and 2 of the questionnaire concerning OMT prescription, dialogue with the patient, associated psychotropic drug prescription, and orientation were considered as a change in therapeutic strategy. RESULTS: A total of 429 questionnaires have been collected. Among them, 315 showed at least 1 change in therapeutic strategy (73.4%). CONCLUSIONS: This study highlighted the important benefits brought by the urine test strip in managing patients under opiate maintenance treatment. Urine test strips provided an immediate answer that allowed physicians to optimize their therapeutic strategy. However, regulatory evolutions would be necessary to ease their implantation