Methadone blood assay by the FPIA technique: application to the monitoring of patients in maintenance treatment to opiates

Abstract

A large inter-individual variability in methadone pharmacokinetics is observed in patients under maintenance treatment for major addiction to opiates. Therefore an individual dose titration of methadone is necessary, based on clinical response, i.e. symptoms of overdosage or withdrawal syndrome, but these symptoms are unspecific. However, a poor response to methadone treatment (asking for drug compliance) or the possibility of drug interactions may require the determination of methadone blood concentrations. Therapeutic drug monitoring (TDM) of those patients is performed using methadone trough blood concentrations measured by chromatography (GC or HPLC: reference methods) or by immunoassay, which gives more rapid results. A review of the literature led us to use the fluorescence polarisation immunoassay (FPIA technique) performed on a TDx-FLx analyzer. We confirmed the lack of "matrix effect" and FPIA was compared to GC-MS (gas chromatography-mass spectrometry) on patients samples. According to the literature, a methadone trough serum concentration target of 400 ng/mL is recommended; results under 100 ng/mL are considered as clinically ineffective, whereas methadone concentrations above 1000 ng/mL are frequently associated with drug toxicity. The linearity domain of the technique stays between 50 and 500 ng/mL, which is satisfactory. We describe some clinical cases from the Methadone Treatment Center of Tours (Centre Port-Bretagne), which showed that methadone blood concentration measurement may be helpful to achieve the optimal dose of methadone in each patient.