Study protocol: stability of morphine injected without preservative, delivered with a disposable infusion device

Abstract

Morphine hydrochloride solutions stored in disposable infusion devices degraded very slowly, particularly when preserved with sodium metabisulphite. The solutions are stable over 5 days, the maximum period of storage normally required when using disposable infusers.

Hplc–dad Method for Studying the Stability of Solutions Containing Morphine, Dexamethasone, Haloperidol, Midazolam, Famotidine, Metoclopramide, and Dimenhydrinate

“…Mixing drugs will prevent multiple perfusions. The stability of single drugs has also been reported by numerous authors (3)(4)(5)(19)(20)(21). Most of the stability studies have been carried out on binary drug mixtures (9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

“…Many researchers have studied the stability of morphine solutions under different conditions of conservation (3)(4)(5). It has been found that the decomposition of morphine is accelerated in alkaline pH (3) and depends on the presence of oxygen (5).…”

“…The degradation products of morphine are pseudo-morphine and morphine-N-oxide and other minor products (3). Morphine can undergo a dimerization reaction when it is stored without preservatives producing pseudomorphine (4).…”

“…Just after preparing the mixture of drugs and then after 4,8,12,24, 48, 72, 96 h, the physical appearance of each solution was observed, and drug concentrations were controlled. Five drug mixtures used for palliative care were stored in polypropylene syringes at different temperatures (25 • C, 4 • C) up to 96 h. These mixtures were: 1)…”

In vitro evaluation of the potential role of sulfite radical in morphine-associated histamine release

“…Most of the morphine used in both clinical practice and for clinical investigations contains sodium bisulfite as a preservative [8]. Until the mid 1980's sulfite preservatives were generally considered universally safe; however, their status was changed after the receipt by the FDA of more than 250 reports of serious and life-threatening reactions related to sulfite exposure through both diet and therapeutic agents [9,10].…”