Stability of high-dose morphine chloride injection upon heat sterilization: comparison of UV-spectroscopy and HPLC

Abstract

Aarau, CH-5001 h r a u , Switzerland SUMMARYThe stability of a preservative-free morphine chloride solution for intravenous or intrathecal use manufactured at a concentration of 40 mglml, near the solubility limit in water, was studied. The influence of heat and oxygen on morphine content was measured with and without autoclaving, and after additional thermal and oxidative stress. The morphine injection was stable during steam sterilization at 121°C for up to I80 min if the solution was adjusted to a pH of 3. High-performance liquid chromatography with W detection (HPLC) and direct W spectroscopy (W) (the latter available in most hospital pharmacies for analytical purposes) were compared for specificity, precision and appropriateness for content and stability assessment of morphine solutions. UV could only be used for quantification of undecomposed morphine. Morphine degradation products of stressed solutions interfered with the direct W assay of morphine at 286 nm, whereas these interfering components were separated by the ion-pair reversed-phase HPLC used. The results demonstrate that even in the absence of stabilizers, morphine chloride solutions may safely be sterilized for 15 min at 121°C. The HPLC method was shown to be sufficiently sensi-

Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics

“…Computed and measured temperatures at representative locations for times before, during and immediately after actuation appear in Figure 2E. The average temperature of the fluid in the reservoir remains in a range (< 60 °C) compatible with many pharmacologically active compounds (Callahan et al, 2001; Joyce et al, 1984; Steger et al, 1996). Calculations based on a simplified fluid dynamics model (see SI for details) indicate that the fluid cools significantly as it flows down the microfluidic channels before penetrating the targeted tissue (< 0.1 °C higher than the temperature of the surroundings).…”

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).…”

“…HPLC methods for determining the drugs involved in this study have already been reported (3)(4)(5)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) …”

Stability of octreotide acetate decreases in a sodium bisulfate concentration-dependent manner: compatibility study with morphine and metoclopramide injections

“…Morphine (MOR) 1% and 4% are sold in the form of injections in Japan; however, SBS is used as a stabiliser in the 4% preparation only because the concentration of MOR hydrochloride is close to its solubility, 0.178 mM (about 5.7% (W/V)). 10 Although metoclopramide (MET) injections generally contain SBS or other stabilisers (such as sodium citrate) as an additive to stabilise the pH, this depends on the manufacturers. Previous studies have demonstrated that MOR and MET are compatible with OCT because no changes were observed in appearance, such as precipitation; however, the presence or absence of SBS as well as the hydrolysis of OCT were not described.…”