Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient-controlled analgesic devices

Abstract

Published reports regarding the stability of morphine are at variance, especially in syringes used in patient-controlled analgesia (PCA) devices. In addition to the effects of container type and vehicle, reasons for this variation include the effect of excipients temperature and light during storage. Furthermore, the literature varies regarding the mechanisms of decomposition for morphine. To our knowledge, the stability of meperidine (pethidine) stored in plastic syringes has not been reported. The purposes of this study were to investigate the stability of morphine sulphate (1 and 5 mg/ml) and meperidine hydrochloride (5 and 10 mg/ml) in plastic syringes for use in PCA devices for a duration of 12 weeks, and evaluate the influence of light (240 foot-candles), temperature (-20, 4 and 23 degrees C), diluent (5% dextrose or normal saline), and drug concentration on the stability of these narcotic analgesics. Samples were taken bi-weekly for solutions protected from light and weekly for solutions exposed to light. Morphine sulphate and meperidine hydrochloride concentrations were quantified using independent, stability-indicating, high performance liquid chromatographic assays. The within-day and between-day coefficients of variation for these assays were < or = 4% over each of the concentration ranges studied. Under the conditions of this study, it is proposed that although decomposition of morphine to its main product, pseudomorphine, can be interpreted using first-order kinetics, consecutive (to form the N-oxide) and parallel mechanisms (to form apomorphine) exist. Morphine solutions were more stable in normal saline than in 5% dextrose. Shelf-life data indicate that morphine is stable for at least 6 weeks when protected from light.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacokinetics of morphine and morphine glucuronide metabolites after subcutaneous bolus injection and subcutaneous infusion of morphine

“…Although it is conceivable that the syringe driver delivered less than the full volume of solution contained in the syringes, this was not noted during the study. Other studies have reported that morphine is stable for several days [25], weeks [26] and even months [27] when stored in plastic syringes and/or PCA devices, and our own stability study indicated no loss of drug from absorption onto plastic during a 24 h incubation period.…”

Improved Morphine-Loaded Hydrogels for Wound-Related Pain Relief

“…As the development of a yellow to brownish colour usually goes together with the formation of pseudomorphine and morphine N-oxide, it was also suggested that the discolouration is due to further degradation of these products [40]. It has been reported that when stored in syringes unprotected from light, morphine solutions showed up to 6-fold acceleration of the degradation when compared to the solutions stored under protection from light, presenting less than 50% of the initial concentration of morphine after 12 weeks [44]. Therefore, to avoid such degradation the F1-MH gel packed in unidose transparent syringes was further packed into a secondary packaging consisting of an opaque bag for light protection.…”

Stability of Fentanyl Citrate, Hydromorphone Hydrochloride, Ketamine Hydrochloride, Midazolam, Morphine Sulfate, and Pentobarbital Sodium in Polypropylene Syringes

“…Published chemical stability studies are available for fentanyl 50 mcg/mL [ 1 ], fentanyl 5 mcg/mL [ 2 ], hydromorphone 100 mcg/mL [ 3 ], ketamine 10 mg/mL [ 4 ], midazolam 5 mg/mL [ 5 ], and morphine 1 mg/mL [ 6 ] concentrations in syringes. Yet, these referenced studies did not extend to the desired 100 day limit.…”