Stability of Ketamine-Propofol Mixtures for Procedural Sedation: RESULTS

9 Dec
2010

There was no significant change in the pH of either solution after 1 or 3 h of storage at room temperature and exposure to light. The average pH of the 50:50 mixture was initially 4.98 and was nearly the same (4.99) 3 h later. For the 30:70 mixture, the average pH was 5.16 initially and 5.15 after 3 h of storage. There were no visible signs of separating or cracking of the emulsion after 3 h of storage in polypropylene syringes. Furthermore, there was no apparent change in the white milky colour and no evidence of gas formation after 3 h.

Table 1. Stability of 50:50 Mixture of Ketamine (10 mg/mL) and Propofol (10 mg/mL)


% of Initial Concentration Remaining

Drug

Initial concentration (mg/mL)

After 1 h After 3 h

Ketamine

5.2 ± 0.06

99.5 ± 1.2 99.5 ± 0.7

Propofol

4.9 ± 0.27

97.3 ± 2.8 101.5 ± 1.3

*Stored in polypropylene syringes, at room temperature (23°C), with exposure to light.

Chromatograms of acidic and alkaline forced-degradation samples showed no interfering peaks after 146 h. Purity testing confirmed that the parent peaks from the degraded samples remained pure. Analysis of the standard curve samples using the propofol method gave a linear correlation (r2) value of 0.9944, with an accuracy of 102.5% ± 2.2%. Intraday variance was 1.13% over a 14-h period. Both propofol and internal standard peaks in the test samples were pure, as indicated by UV spectral and multiple-wavelength analysis. Peak shape did not change over the course of the study. There was an decrease of approximately 1.5% in concentration after filtering.

Table 2. Stability of 30:70 Mixture of Ketamine (10 mg/mL) and Propo

% of Initial Concentration Remaining

Drug

Initial concentration (mg/mL)

After 1 h After 3 h

Ketamine

3.3 ± 0.06

97.8 ± 1.5 99.0 ± 0.9

Propofol

6.8 ± 0.11

101.3 ± 2.3 97.6 ± 1.1

*Stored in polypropylene syringes, at room temperature (23°C), with exposure to light.

Linear correlation for analysis of the standard curve sam­ples using the ketamine method yielded an r2 value of 0.9999 with an accuracy of 99.7% ± 1.0%. Over a 30-h period, the intraday variance was 0.68%. None of the ketamine degrada­tion peaks interfered with the parent compounds. Purity of the ketamine peak was confirmed by multichannel and UV spectral analysis, as well as peak shape and retention times. Spectra from the parent compounds were highly correlated with those from the reference material (> 0.990).

Figure 1. Chromatogram

Figure 1. Chromatogram of ketamine in 50:50 mixture of ketamine and propofol. Peak 1 (10.8 min) represents the internal standard, and peak 2 (20.4 min) is the ketamine.

Chromatography results for samples of the 50:50 mixture with the ketamine method, to check for interfering peaks, are shown in Figure 1. Figure 2 illustrates a typical chromatogram for the 50:50 sample using the propofol assay method. There were no interfering peaks in either case.

Figure 2. Chromatogram of propofol

Figure 2. Chromatogram of propofol in 50:50 mixture of ketamine and propofol. Peak 1 (5.2 min) represents the internal standard, and peak 2 (8.4 min) is the propofol.

Drug concentrations in both combinations remained above 97% after storage at room temperature with exposure to light for up to 3 h (Tables 1 and 2). No new peaks appeared in any of the chromatograms.

top