Stability of methadone hydrochloride in 0.9% sodium chloride injection in single-dose plastic containers

Denson, Donald D.; Crews, James C.; Grummich, K. W.; Stirm, Eric J.; Sue, Caron A.

doi:10.1093/ajhp/48.3.515

Cited by 9 publications

(7 citation statements)

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“…According to USP oral solutions of methadone and phenobarbital should be stored protected from light. Similar studies are found in the literature for methadone, but all of them the API concentration in solution is higher than the required for the specific objectives of our study 21 . It is well-known that a concentrated solution is likely to be more stable than the same product in a diluted form 22 .…”

Section: Discussionsupporting

confidence: 85%

Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome

Provenza¹,

Calpena²,

Mallandrich³

et al. 2015

Pharmaceutical Development and Technology

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Section: Discussionsupporting

confidence: 85%

Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome

Provenza¹,

Calpena²,

Mallandrich³

et al. 2015

Pharmaceutical Development and Technology

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“…The stability of methadone hydrochloride in aqueous solutions is good. 9,10 Methadone hydrochloride for injection diluted in saline solutions (at 1, 2, or 5 mg/mL) was reported to be stable for at least 4 weeks at room temperature. 9 Solutions of methadone hydrochloride prepared in orange-flavoured Tang® drink mix for oral administration were stable for 91 days at room temperature or under refrigeration.…”

Section: Resultsmentioning

confidence: 99%

“…9,10 Methadone hydrochloride for injection diluted in saline solutions (at 1, 2, or 5 mg/mL) was reported to be stable for at least 4 weeks at room temperature. 9 Solutions of methadone hydrochloride prepared in orange-flavoured Tang® drink mix for oral administration were stable for 91 days at room temperature or under refrigeration. 10 With methadone hydrochloride injection USP no longer available, this study proposes a compounded methadone hydrochloride solution for injection (5 mg/mL) prepared from bulk powder and saline solution as an alternative for pediatric administration.…”

Section: Resultsmentioning

confidence: 99%

Stability of Methadone Hydrochloride for Injection in Saline Solution

Friciu

Alarie

Beauchemin

et al. 2020

CJHP

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Background: Until October 2014, methadone hydrochloride forinjection (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 highperformance 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.RÉSUMÉContexte : Jusqu’en octobre 2014, le chlorhydrate de méthadone pourinjection (10 mg/mL) était disponible au Canada à l’aide du Programme d’accès spécial de Santé Canada. Dilué à 5 mg/mL dans une solutionsaline, il était utilisé en pédiatrie contre les douleurs aigües et celles liées au cancer. Plus récemment, le département de pharmacie du Centre hospitalier universitaire Sainte-Justine de Montréal au Québec a proposé de préparer une solution de chlorhydrate de méthadone pour injection (5 mg/mL) à partir d’une poudre en vrac et d’une solution saline en vue de l’administrer en pédiatrie.Objectif : Évaluer la stabilité de la préparation proposée.Méthodes : Les préparations de chlorhydrate de méthadone diluées dans une solution saline se font à partir d’une poudre en vrac, elles sont stockées dans des fioles en verre transparent pendant180 jours à la température ambiante (25 °C) ou réfrigérées (5 °C) et sont soumises à des tests les jours 0, 7, 14, 30, 60, 90 et 180. L’apparence des solutions et la présence de substances particulaires ont fait l’objet d’une évaluation. Une méthode de chromatographie liquide à haute performance (CLHP) indiquant la stabilité a été développée pour tester la concentration de methadone dans le temps.Résultats : Aucun changement notable de l’apparence de la solution de méthadone n’a été observé, le nombre de particules ne dépassait pas les limites précisées par l’United States Pharmacopeia et aucune croissance microbienne n’a été observée. L’analyse CLHP a indiqué que la concentration de méthadone était demeurée au-delà de 90% durant toute la durée de l’étude.Conclusions : Le chlorhydrate de méthadone pour injection préparé à partir de poudre en vrac dans une solution saline à une concentration de5 mg/mL est resté chimiquement stable pendant au moins 180 jours lorsqu’il était stocké dans des fioles en verre transparent à 5 °C et à 25 °C

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“…Therefore, there would not be suitable for our work. Methadone stability studies have also been described, but the methadone determination technique is either the USP one, those previously shown in the literature, GC [ 23 ] or spectrophotometry [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a HPLC-UV method for methadone hydrochloride quantification in a new oral solution with preservatives to be implemented in physicochemical stability studies

et al. 2022

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Purpose The Pharmacy Service of the Infanta Leonor University Hospital acquires, compounds, distributes and dispenses more than 3000 L of methadone oral solution to Drug Addiction Patients Centers per year. Our purpose is to develop and validate an improved high performance liquid chromatography (HPLC) method to quantify methadone hydrochloride in a new oral solution with methylhydroxybenzoate (methylparaben) and propylhydroxybenzoate (propylparaben) to be implemented in physicochemical stability studies that allow to provide more information and even to increase the beyond-use date. Methods A HPLC-Agilent® 1100 equipment, comprising a quaternary pump and an ultraviolet diode-array-detector (DAD) was used. An analytical method development and validation was completed. The curve was constructed from methadone working concentrations of 75–125% (7.5, 9.0, 10.0, 11.0 and 12.5 mg/mL) to assess the linear relationship between the concentration of the analyte and the obtained areas. Precision and accuracy were calculated. Detection and quantification limit (LD, LQ) were estimated using the EURACHEM method. Forced-degradation studies were also performed. Results Chromatographic conditions were: flow rate 1.6 mL/min; mobile phase 55% acetonitrile and 45% sodium phosphate 25 mM (pH = 10); injection volume was 5 µL. The column was a Waters-XTerra™ RP18, maintained at 40 °C. DAD was λ = 254 nm. Retention times for methadone, methylparaben and propylparaben were 4.34, 0.70 and 0.88 min respectively. The method was linear (y = 284.3x − 97.8, r = 0.996). Instrumental precision was 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%. The recovery percentage was 101.5 ± 1.5%. LQ and LD were 2.18 µg/mL and 2.0 µg/mL respectively. The most destabilizing conditions were oxidizing and alkaline. The chromatograms confirmed no interference with the methadone signal. Conclusions The HPLC method has proved to be valid and reproducible for methadone quantification in a new oral solution with methylparaben and propylparaben. This assay is a rapid, simple and reliable technique that can be used in daily analysis and physicochemical stability studies.

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Stability of methadone hydrochloride in 0.9% sodium chloride injection in single-dose plastic containers

Cited by 9 publications

References 0 publications

Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome

Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome

Stability of Methadone Hydrochloride for Injection in Saline Solution

Development and validation of a HPLC-UV method for methadone hydrochloride quantification in a new oral solution with preservatives to be implemented in physicochemical stability studies

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