Background and importance On the basis of resolution 189/2018 published by our city health council, the hospital pharmacy service was entrusted with the centralisation of the procedure for the acquisition, compounding, distribution and dispensing of methadone to drug addicts in integral attention centres. In order to improve and increase the beyond use date (BUD) of methadone oral solutions, we carried out a physicochemical stability study.

Aim and objectives To develop an analytical method and validation to carry out a physicochemical stability study of two oral solutions of methadone to increase their BUD. Method development should be made in an effective and reproducible manner.

Material and methods The study was carried out on two formulations of methadone 10 mg/mL, which were prepared with and without parabens as preservatives. A high performance liquid chromatography (HPLC) Agilent 1100 was used, provided with a quaternary pump and an ultraviolet diode array detector to determine methadone. First we carried out the analytical method development to achieve the analytical performance characteristics. Then we performed validation of the analytical method obtaining linearity, instrumental intra-assay and inter-assay precision, and accuracy and recovery percentage.

Results Chromatographic conditions were: flow rate 1.6 mL/min, 55% acetonitrile and 45% phosphate buffer (adjusted to pH=10) as the mobile phase. Injection volume was 50 µL, the temperature in the column compartment was 40°C. The column used was the Xterra C18 because methadone pKa is 8.3. Retention time for methadone was 4.5 min and for parabens 1.5 min.

The final methadone determination method was validated for a standard of 10 mg/mL and applied for the determination of methadone with two parabens. The most relevant results were: correlation coefficient r=0.9957 for methadone in the range tested (7.5–12.5 mg/mL); instrumental precision 0.33% for standards (n=10); intra-assay precision 0.53% (n=6) and inter-assay precision 1.95% (n=12). The relative standard deviation percentage for accuracy was 1.28%, and the percentage recovery was 101.5 ±1.5%.

Conclusion and relevance Analytical method development and validation procedures are vital in the discovery and development of drugs and pharmaceuticals to ensure performance of the method. The proposed HPLC conditions to determine methadone were proved to be valid and reproducible for carrying out physicochemical stability studies of different methadone oral solutions.

References and/or acknowledgements No conflict of interest.