Highly selective electrode for potentiometric analysis of methadone in biological fluids and pharmaceutical formulations

• An accurate potentiometric method was developed for methadone analysis.
• Sub-micromolar concentrations of methadone were determined accurately and precisely.
• The sensor was used in recovery of methadone from blood serum and urine samples.
• A wide linear range was obtained (> 5 orders of magnitude).
• The lifetime of the electrode was > 5 months.

In order to develop a fast and simple procedure for methadone analysis in biological fluids, a graphite paste electrode (GPE) was modified with the ion-pair of methadone–phosphotungstic acid, and multiwalled carbon nanotubes (MWCNTs). Optimized composition of the electrode with respect to graphite powder:paraffin oil:MWCNTs:ion pair, was 58:30:8:4 (w/w%). The electrode showed a near-Nernstian slope of 58.9 ± 0.3 mV/decade for methadone in a wide linear range of 1.0 × 10− 8–4.6 × 10− 3 M, with a detection limit of 1.0 × 10− 8 M. The electrode response was independent of pH in the range of 5–11, with a fast response time (~ 4 s) at 25 °C. The sensor showed high selectivity and was successfully applied to the determination of sub-micromolar concentrations of methadone in human blood serum and urine samples, with recoveries in the range of 95–99.8%. The average recovery of methadone from tablets (5 mg/tablet) by using the proposed method was 98%. The life time of the modified electrode was more than 5 months, due to the characteristic of GPE which can be cut off and fresh electrode surface be available. A titration procedure was performed for methadone analysis by using phosphotungstic acid, as titrating agent, which showed an accurate end point and 1:1 stoichiometry for the ion-pair formed (methadone:phosphotungstic acid). The simple and rapid procedure as well as excellent detection limit and selectivity are some of the advantages of the proposed sensor for methadone.