Stability of Hydromorphone-Ketamine Solutions: DISCUSSION

To the authors’ knowledge, the only published stability analysis of hydromorphone and ketamine in normal saline was conducted by Walker and others in 2001. In their sophisticated 2-part study (24-h physical compatibility of 12 concentration combinations in the first part of the study and 24-day compat­ibility and chemical stability of 4 concentration combinations in the second part), the investigators determined that concentration combinations of 1.0 and 0.5 mg/mL, 20.0 and 0.5 mg/mL, 1.0 and 20.0 mg/mL, and 20.0 and 20.0 mg/mL (hydromorphone and ketamine, respectively) were stable when stored in glass at 4°C or 23°C for 24 days.
Although PCA with hydromorphone—ketamine may hold promise for children with mucositis who have inadequate analgesia with conventional hydromorphone PCA, no stability data on hydromorphone—ketamine solutions specifically for pediatric use were available. In addition, no data were found regarding the stability of these solutions when stored in plastic syringes or IV bags. Thus, before such mixtures were adminis­tered to patients (as in the proposed study described above), the stability of 3 different mixtures of hydromorphone and ketamine (0.2 and 0.2 mg/mL, 0.2 and 0.6 mg/mL, and 0.2 and 1.0 mg/mL, respectively), prepared in NS, was assessed for a period of up to 7 days, with storage at room temperature in glass bottles, plastic syringes, or IV bags.
In the daily analysis of samples, there were no notable changes in pH or colour in any of the solutions stored in glass bottles, plastic syringes, or IV bags at 25°C for 7 days. All formulations of hydromorphone—ketamine maintained at least 90% of their initial concentration.

The absence of bacterial growth in all incubated samples demonstrated that sterility of these preparations was maintained under the study conditions. However, there is a potential risk for contamination or the potential for bacterial growth in a contaminated sample if it were stored at 25°C. Although Canadian pharmacies are not subject to the standards of USP (United States Pharmacopeia) chapter <797>, it remains the best current document integrating information about degradation rate (expiry dates) and sterility. It specifies that storage at room temperature for low-risk compounding should not exceed 48 hours. Given that sterility can change according to site, equipment, operator, and procedures used, the following cautions are suggested: (i) the finding of no growth after storage for 5 days at 25°C in this study does not mean that all combined solutions of hydromorphone and ketamine will be sterile, and (ii) before using an expiry date of 7 days for any solution stored at room temperature, consideration should be given to the contamination rate within the institution’s IV additive program. Cialis Jelly

Category: Drugs

Tags: high- performance liquid chromatography, hydromorphone, ketamine, pain, patient-controlled analgesia, pediatrics, stability

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