Stability of Hydromorphone-Ketamine Solutions: RESULTS

hydromorphone

For the standard curve generated as described above, regression analysis of the peak area ratio of hydromorphone and ketamine (standards) to internal standard versus concentration demonstrated linearity over the working range of the standard concentrations, with coefficients of determination (r2) greater than 0.990 (n = 4). The mean deviation between the nominal and observed concentrations was below 1.5% (i.e., accuracy of 98.5%). The intraday (n = 4) and interday (n = 4) coefficients of variation for the 4 different concentrations of standards were within acceptable limits (i.e., < 10%): 2.3% and 3.1%, respectively, for hydromorphone and 0.70% and 3.40%, respectively, for ketamine in the combined solution with 0.25 mg/mL of each drug; 1.99% and 2.56%, respectively, for hydromorphone and 2.23% and 3.09%, respectively, for ketamine in the combined solution with 0.15 mg/mL of each drug; 1.29% and 3.80%, respectively, for hydromorphone and 1.39% and 3.02%, respectively, for ketamine in the solution with 0.05 and 0.09 mg/mL of the respective drugs; and 0.18% and 3.63% respectively, for hydromorphone and 0.21% and 1.57%, respectively, for ketamine in the solution with 0.03 and 0.08 mg/mL of the respective drugs.

The retention times were, on average, 3.87 min for hydro­morphone, 5.86 min for ketamine, and 7.60 min for the inter­nal standard, naloxone. When the hydromorphone—ketamine solution was subjected to degradation, the hydromorphone peak completely disappeared and the ketamine peak was reduced by 40% relative to that of the standard curve. No interfering peaks were detected (Figure 1). Thus, the HPLC method was deemed capable of indicating stability. buy levitra 20 mg

Table 1. Mean pH of Mixtures of Hydromorphone and Ketamine After 7 Days of Storage at 25°C

Drug Concentration (mg/mL)

Container

Hydromorphone

Ketamine

pH (Mean ± SD)


Glass bottles


0.20


0.20


4.682 ±
0.096


0.20


0.60


4.768 ±
0.017


0.20


1.00


4.764 ±
0.011


Syringes


0.20


0.20


4.486 ± 0.053


0.20


0.60


4.596 ±
0.018


0.20


1.00


4.546 ± 0.028


PVC bags


0.20


0.20


4.542 ± 0.037


0.20


0.60


4.596 ±
0.017


0.20


1.00


4.612 ±
0.027


SD = standard deviation, PVC = polyvinyl chloride.

Each clear solution had a neutral smell. No notable changes in physical appearance, odour, or colour of the solutions were observed over the 7-day storage period. No significant fluctuations in pH were observed (Table 1). viagra jelly

Figure 1. Top Peaks for undegraded samples

Figure 1. Top: Peaks for undegraded samples of hydromorphone at 3.89 min, ketamine at 5.84 min, and the internal standard (naloxone) at 7.58 min. Bottom: Degraded preparation shows disappearance of the hydromorphone peak, a 40% reduction in the ketamine peak, and no interfering peaks. HyMO = hydromorphone, Ket = ketamine, Nal = naloxone, AU = absorbance units.

The HPLC analysis showed that, at room temperature, all 9 mixtures maintained between 90% and 110% of their initial concentrations on every study day. Further­more, more than 95% of the initial hydromorphone and ketamine concentrations remained on day 7, according to linear regression analysis of the concentration—time data. As well, after 5 days of incubation, none of the samples demonstrated any bacterial growth.
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