Stability of Methadone Hydrochloride for Injection in Saline Solution. 2020

M Mihaela Friciu, and Hugo Alarie, and Mylène Beauchemin, and Jean-Marc Forest, and Grégoire Leclair
, MSc, is a Research Associate with the Faculty of Pharmacy, Université de Montréal, Montréal, Quebec, BSc, is a Master of Science candidate in the Faculty of Pharmacy, Université de Montréal, Montréal, Quebec, PharmD, MSc, is a Pharmacist with the Department of Pharmacy, Centre hospitalier universitaire Sainte-Justine, Montréal, Quebec, BPharm, DPH, MSc, is a Pharmacist with the Compounding Service (Fabrication) in the Department of Pharmacy, Centre hospitalier universitaire Sainte-Justine, Montréal, Quebec, BPharm, PhD, is an Associate Professor with the Faculty of Pharmacy, Université de Montréal, Montréal, Quebec.

BACKGROUND Until October 2014, methadone hydrochloride for injection (10 mg/mL) was available in Canada through Health Canada's Special Access Programme. Diluted to 5 mg/mL in saline, it was used in pediatrics for acute and cancer-related pain. More recently, the department of pharmacy of the Centre hospitalier universitaire Sainte-Justine in Montréal, Quebec, proposed compounding a solution of methadone hydrochloride for injection (5 mg/mL) from bulk powder and saline solution for pediatric administration. OBJECTIVE To assess the stability of the proposed compounded preparation. METHODS Solutions of methadone hydrochloride in saline were prepared from bulk powder and stored in clear glass vials for up to 180 days at room temperature (25 °C) or with refrigeration (5 °C), with testing on days 0, 7, 14, 30, 60, 90, and 180. The appearance of the solutions and presence of particulate matter were assessed. A stability-indicating high-performance liquid chromatography (HPLC) method was developed to assay the concentration of methadone over time. RESULTS No notable changes in appearance of the methadone solution were observed, particle counts did not exceed limits specified by the United States Pharmacopeia, and no microbial growth was observed. The HPLC analysis showed that the concentration of methadone remained above 90% on all study days. CONCLUSIONS Methadone hydrochloride for injection prepared from bulk powder in saline solution at a concentration of 5 mg/mL remained chemically stable for at least 180 days when stored in clear glass vials at 5 °C and at 25 °C.

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