3PC-016 Stability evaluation of four methadone intravenous mixtures used in palliative sedation

<h3>Background and Importance</h3> In palliative care, drug infusions containing opioids are commonly used, but stability data regarding methadone mixtures are limited. <h3>Aim and Objectives</h3> To evaluate the physicochemical stability of four quaternary mixtures containing methadone in different diluents and storage conditions, as well as to validate a high-performance liquid chromatography (HPLC) method for this purpose. <h3>Material and Methods</h3> Composition of four intravenous mixtures to be studied was agreed upon by a multidisciplinary team including pharmacists and palliative care physicians: methadone 5 mg, midazolam 30 mg, buthylscopolamine 60 mg and haloperidol 5 mg in 250 mL saline (M1) and 500 mL 1/3 glucosaline (M2); methadone 250 mg, midazolam 250 mg, buthylscopolamine 240 mg and haloperidol 30 mg in 250 mL saline (M3) and 500 mL 1/3 glucosaline (M4). Two samples of each mixture were respectively stored at light exposed/protected conditions during 48 hours at room temperature. From each sample 1 mL was filtered and analysed by triplicate. Visual inspection, pH measurement and drug content were considered at 0, 24 and 48 hours. Stability was defined as the absence of visual changes, not significant pH variation and a remaining drug concentration of 90–110% of the initial concentration. Drug quantification was performed by RP-HPLC-DAD. Chromatographic conditions were: flow rate 0.6 mL/min, mobile phase monopotassium phosphate 10 mM buffer (pH=2.5): methanol (gradient: 0–10 min 75:25, 10–18 min 60:40, 19–23 min 75:25), column C18, 100x4.6 mm, 2.6µm, temperature 25°C, injection volume 1μL, detector wavelength 220 nm and analysis time 23 min. <h3>Results</h3> A linear regression equation was obtained for each drug studied to validate method. Coefficient of determination showed the method was linear in the range of concentrations considered. Time of retention for each drug was, in minutes: butylscopolamine 8.54; midazolam 11.23; haloperidol 12.37 and methadone 13.76. Precision and accuracy were also evaluated. Selectivity and specificity were confirmed by 2D-ultraviolet spectral analysis. After 24 and 48 hours, none of the mixtures experienced visual changes. pH values among days did not change significantly either. The remaining concentration of all drugs was considered acceptable according to the established considerations. <h3>Conclusion and Relevance</h3> The HPLC method was successfully validated. All four methadone mixtures remained stable for 48 hours under both light exposed and protected conditions. This confirms their stability and suitability for use over this period. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest