HPLC–DAD METHOD FOR STUDYING THE STABILITY OF SOLUTIONS CONTAINING MORPHINE, DEXAMETHASONE, HALOPERIDOL, MIDAZOLAM, FAMOTIDINE, METOCLOPRAMIDE, AND DIMENHYDRINATE

Abstract

The objectives of this study were to evaluate both the compatibility and the stability of morphine when mixed with different drugs and to provide recommendations for appropriate conservation conditions. 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) Morphine, Dexamethasone, Octreotide; 2) Morphine, Dexamethasone, Haloperidol; 3) Morphine, Octreotide, Haloperidol, Midazolam, Famotidine; 4) Morphine, Haloperidol, Famotidine, Metoclopramide; 5) Octreotide, Haloperidol, Famotidine, Metoclopramide, Dimenhydrinate. Drug mixtures were prepared in NaCl 0.9%, in order to obtain a 100 mL final solution containing the maximum daily dose of each component. For the separation and quantification of active ingredients, 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®, Eclipse XDB C₁₈) column under elution 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 observed, and drug concentrations were controlled. Stability was assumed if the loss after 96 h was less than 10% of the initial concentration. Mixture number [2] was incompatible when drugs were mixed. Mixing haloperidol and dexamethasone gave rise to the formation of a white precipitate. Mixture [3] was stable and compatible at 25°C, but incompatible at 4°C due to crystallization of haloperidol. All the other drug mixtures were stable and compatible both at 4°C and 25°C for 96 h.

ACKNOWLEDGMENTS

We wish to thank the department of palliative care of the Royal Victoria Hospital in Montreal for Research Funding.