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

摘要

SUMMARYPublished 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‐candies), temperature (‐20, 4 and 23d̀C), 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 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. SheIf‐life data indicate that morphine is stable for at least 6 weeks when protected from light. Exposure to light accelerates morphine decomposition two to six‐fold depending on the concentration, and the shelf‐life is reduced to about 1 week in some instances.Meperidine solutions in both vehicles under all conditions had shelf‐lives of at least 12 weeks. No effects of light were detected and no changes in solution colour were observed.This study illustrates that patients using PCA devices must be advised about shelf‐lives as well as correct storage conditions to protect solutions of these drugs from environmental factors that may alter shelf‐lives. Pharmacists should also note that other formulation factors such as: antioxidants, preservations, buffers, impurities, and the source and quality of containers, may significantly alter