HPLC‐DAD Methods for Studying the Stability of Solutions Containing Hydromorphone, Ketorolac, Haloperidol, Midazolam, Famotidine, Metoclopramide, Dimenhydrinate, and Scopolamine

Abstract

The objectives of this study were to evaluate both the compatibility and the stability of hydromorphone when mixed with different drugs and to provide recommendations for appropriate conservation conditions. Four drug mixtures used for palliative care were stored in polypropylene syringes at different temperatures (25°C and 4°C) up to 96 hours. These mixtures were: M1: hydromorphone 10.00 mg mL⁻¹, midazolam 1.00 mg mL⁻¹, famotidine 0.40 mg mL⁻¹; M2: hydromorphone 10.00 mg mL⁻¹, metoclopramide 0.50 mg mL⁻¹, haloperidol 0.50 mg mL⁻¹; M3: hydromorphone 10.00 mg mL⁻¹, ketorolac 1.50 mg mL⁻¹, metoclopramide 0.50 mg mL⁻¹, famotidine 0.40 mg mL⁻¹; and M4: hydromorphone 10.00 mg mL⁻¹, dimenhydrinate 5.00 mg mL⁻¹, haloperidol 0.50 mg mL⁻¹, famotidine 0.40 mg mL⁻¹, scopolamine 0.04 mg mL⁻¹. 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 fast, precise, accurate, and sensitive methods were developed. Drugs were separated using a high performance liquid chromatography‐diode array detector (HPLC‐DAD) with a Zorbax^® Eclipse XDB C₁₈ column under gradient elution. Just after preparing the mixture of drugs and then after 4, 8, 12, 24, 48, 72, and 96 hours, the physical appearance of each solution was observed and drug concentrations were controlled. Stability was assumed if the loss after 96 hours was less than 10% of the initial concentration.

Keywords:

• HPLC‐DAD
• Hydromorphone
• Ketorolac
• Haloperidol
• Midazolan
• Famotidine
• Metoclopramide
• Dimenhydrinate
• Scopolamine

Acknowledgment

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