HPLC-DAD method for studying the stability of solutions containing morphine, dexamethasone, haloperidol, midazolam, famotidine, metoclopramide, and dimenhydrinate

The objectives of this study were to evaluate both the compatibility and th e stability of morphine when mixed with different drugs and to provide reco mmendations for appropriate conservation conditions. Five drug mixtures use d for palliative care were stored in polypropylene syringes at different te mperatures (25 degreesC, 4 degreesC) up to 96 h. These mixtures were: 1) Mo rphine, Dexamethasone, Octreotide; 2) Morphine, Dexamethasone, Haloperidol; 3) Morphine, Octreotide, Haloperidol, Midazolam, Famotidine; 4) Morphine, Haloperidol, Famotidine, Metoclopramide; 5) Octreotide, Haloperidol, Famoti dine, Metoclopramide, Dimenhydrinate. Drug mixtures were prepared in NaCl 0 .9%, in order to obtain a 100 mt final solution containing the maximum dail y dose of each component. For the separation and quantification of active i ngredients, a fast, precise, accurate, and sensitive method was developed. Drugs were separated using HPLC-DAD (High performance liquid chromatography -diode array detector) with a Zorbax(R) Eclipse XDB C-18) column under elut ion gradient. 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 observ ed, and drug concentrations were controlled. Stability was assumed if the l oss after 96 h was less than 10% of the initial concentration. Mixture numb er (2) was incompatible when drugs were mixed. Mixing haloperidol and dexam ethasone gave rise to the formation of a white precipitate. Mixture (3) was stable and compatible at 25 degreesC, but incompatible at 4 degreesC due t o crystallization of haloperidol. All the other drug mixtures were stable a nd compatible both at 4 degreesC and 25 degreesC for 96 h.