Stability of Vancomycin 25 mg/mL in Ora-Sweet: RESULTS

6 Jan
2011

Regression analysis of the peak area ratios of vancomycin to internal standard versus vancomycin standard concentrations demonstrated linearity over the range of the concentrations, with coefficient of determination (r2) greater than 0.998 (n = 4). The intraday and interday CVs were less than 10% and therefore within acceptable limits: 2.7% and 5.5%, respective­ly, at 0.31 mg/mL; 7.22% and 7.37%, respectively, at 0.62 mg/mL; 2.17% and 8.76%, respectively, at 1.25 mg/mL; and 0.70% and 5.24%, respectively, at 2.5 mg/mL. The intraday and interday accuracies were at least 90% and therefore also within acceptable limits: 96.19% and 99.77%, respectively, at 0.31 mg/mL; 92.22% and 92.22%, respectively, at 0.62 mg/mL; 92.13% and 92.20%, respectively, at 1.25 mg/mL; and 94.57% and 96.17%, respectively, at 2.5 mg/mL. The lower limit of quantitation was 0.25 mg/mL, and the lower limit of detection was 0.0025 mg/mL. The retention times were 1.57 min for vancomycin and 2.59 min for metronidazole (Figures 1A and 1B).

When the first vancomycin solution (in water) was subjected to degradation, the vancomycin peak was reduced by 93% relative to the standard curve, and non-interfering peaks were detected at 1.04 and 1.38 min (Figure 1C). When the vancomycin solution in Ora-Sweet and water was subjected to degradation, the vancomycin peak was reduced by 58%, and non-interfering peaks were detected at 1.00, 1.48, 1.75, and 1.89 min (Figure 1D). Thus, the HPLC method was deemed capable of indicating stability. Viagra Professional

Table 1. Vancomycin Remaining after up to 75 Days of Storage at 4°C in Unit-Dose Cups and in Plastic Bottles

Storage Container; Mean Concentration ± SD (% of Original)t

Study day

Unit-Dose Cups


Plastic Bottles

Initial concentration* (mg/mL)

24.69
±
0.170

(100.0)

25.77
±
1.028

(100.0)

15

25.49
±
1.247

(103.2)

25.73
±
1.899

(99.8)

30

25.77 ± 0.705

(104.4)

24.65 ± 2.232

(95.7)

40

24.86
±
0.612

(100.7)

25.35
±
1.331

(98.4)

50

25.11
±
0.960

(101.7)

25.41
±
0.910

(98.6)

63

24.62 ±
0.747

(99.7)

25.11
±
0.615

(97.4)

75

25.03
±
0.620

(101.4)

26.37 ± 0.791

(102.3)

% remaining on day
75 by linear regression*

99.0

100.9

Lower limit of 95% CI for
%
remaining§

93.6

94.0

CI = confidence interval, SD = standard deviation.
*Nominal concentration was
mg/mL.

tMeasured concentration,reported as mean ± standard deviation of 3 replicate analyses of 3 samples, with percent of
initial (measured) concentration in parentheses.

^Calculated from concentration at day 75 as determined by linear regression and concentration observed at time
0,according to  the following formula: concentration at day 75 * concentration at time 0 x 100.
§Calculated from lower limit of 95%
CI of the slope of the curve relating concentration to time, determined by linear regression,
according to the following formula: lower limit of
95% CI of concentration at day 75 * concentration at time 0 x 100.

There were no notable changes in colour, taste, or pH for vancomycin solutions stored in unit-dose cups at 4°C and 25°C or in plastic bottles at 4°C throughout the 75-day period. In the vancomycin solutions stored in plastic bottles at 25°C, a white precipitate was observed starting on day 63, but there were no notable changes in taste or pH during the 75-day period. On day 0, the mean pH ± SD was 3.69 ± 0.006 for solutions in unit-dose cups to be stored at 4°C, 3.67 ± 0.006 for solutions in unit-dose cups to be stored at 25°C, 3.69 ± 0.010 for solutions in plastic bottles to be stored at 4°C, and 3.68 ± 0.012 solutions in plastic bottles to be stored at 25°C.
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Table 2. Vancomycin Remaining after up to 75 Days of Storage at 23°C in Unit-Dose Cups and in Plastic Bottles



Storage Container; Mean Concentration ± SD (% of Original)t

Study day

Unit-Dose Cups

Plastic Bottles


Initial concentration* (mg/mL)


25.23
±
1.029


(100.0)


24.74
±
0.817


(100.0)


15


24.96 ± 0.203


(98.9)


25.16
±
1.686


(101.7)


30


25.13
±
0.491


(99.6)


23.43
± 0.597


(94.7)


40


25.63
±
1.231


(101.6)


22.69
± 0.647


(91.7)


50


25.45 ± 0.450


(100.9)


23.02
± 0.642


(93.0)


63


22.65
±
0.516


(89.8)


22.71
±
1.107


(91.8)


75


21.95
±
0.333


(87.0)


19.69
±
1.146


(79.6)


%% remaining on day 75 by linear
regression*


87.9


81.9


Lower limit of 95% CI for


74.6


71.0


% remaining§


Time predicted to maintain
at least

90.0%

of initial concentration^


30
days


26 days


CI = confidence interval,
SD
= standard deviation.
*Nominal concentration was
25mg/mL.

tMeasured concentration,reported as mean ± standard deviation of 3 replicate analyses of 3 samples, with percent of
initial (measured) concentration in parentheses.

*Calculated from concentration at day 75 as determined by linear regression and concentration observed at time
0, according to the following formula: concentration at day 75 * concentration at time 0 x 100.
§Calculated from lower limit of 95% CI of the slope of the curve relating concentration to time, determined by linear regression, according to the following formula: lower limit of 95% CI of concentration at day 75 *concentration at time
0
x 100.


^Calculated according to the following formula:
10 *lower limit of the 95% CI of the slope of the curve relating concentration to time (determined by linear regression).

On day 75, the mean pH ± SD was 3.85 ± 0.117 for solutions stored in unit-dose cups at 4°C, 4.06 ± 0.219 for solutions stored in unit-dose cups at 25°C, 3.82 ± 0.156 for solutions stored in plastic bottles at 4°C, and 4.02 ± 0.193 solutions stored in plastic bottles at 25°C. The solutions had a sweet-and- sour taste throughout the period, with subjective palatability (based on a single taster) of 3.5 out of 5 points.  buy kamagra oral jelly

Figure 1. A Chromatogram of a sample

Figure 1. A: Chromatogram of a sample obtained at time 0 and stored for 85 days at -85°C shows vancomycin peak at 1.57 min and internal standard (metronidazole) peak at 2.59 min. B: Chromatogram of a sample obtained on day 75 of storage at room temperature and then stored for 10 days at -85°C shows an additional small degradation peak at 1.35 min. C: Chromatogram of vancomycin solution (in water) after degradation with 1N sodium hydroxide and boiling for 10 minutes shows 2 noninterfering peaks at 1.04 min and 1.38 min and a 93% reduction in the vancomycin peak. D: Chromatogram of vancomycin solution (in Ora-Sweet vehicle and water) after degradation by incubation at 100°C for 18 h shows 4 noninterfering peaks at 1.00, 1.48, 1.75, and 1.89 min and a 58% reduction in the vancomycin peak. AU = absorbance units.

The 95% CI of the slope determined by linear regression indicated that all vancomycin solutions stored in unit-dose cups or plastic bottles at 4°C would maintain at least 93.6% of the initial vancomycin concentration for 75 days (Table 1). However, the solutions stored in unit-dose cups and plastic bottles at 25°C were predicted to maintain only 74.6% and 71.0%, respectively, of the initial concentration on day 75 (Table 2). On the basis of the lower limit of the 95% CI, vancomycin solutions stored at room temperature in unit-dose cups or plastic bottles were predicted to maintain at least 90.0% of initial concentration for 30 and 26 days, respectively, with 95% confidence (Table 2). canadian antibiotics

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