Hospital Pharmacy - November 2017 - 706

706

Hospital Pharmacy 52(10)

Table 1. Stability of Procainamide Hydrochloric Acid (100 mg/mL) Repackaged in Clear Glass Vials.

Temperature, ºC
23
5c
a

% of initial concentration remaininga

Initial
concentration,a
mg/mL

Day 7

Day 14

Day 28

Day 56

Day 91

Day 193

100.2 ± 0.13
94.7 ± 1.5

96.5 ± 1.1
99.9 ± 1.0

94.6 ± 1.9
99.6 ± 0.7

98.4 ± 1.8
99.8 ± 1.1

98.9 ± 1.4
100.0 ± 1.7

97.7 ± 1.7
101.1 ± 0.7

97.5 ± 1.0
99.5 ± 1.2

Mean ± standard deviation (N = 6).

Table 2. Stability of Procainamide Hydrochloric Acid (3 mg/mL) Diluted in Normal Saline Packaged in Polyvinyl Chloride Bags.

Temperature, ºC
23b
5c

% of initial concentration remaininga

Initial
concentration,a
mg/mL

Day 7

Day 14

Day 21

Day 28

Day 56

Day 91

Day 193

2.9 ± 0.03
3.0 ± 0.02

100.8 ± 2.1
100.8 ± 1.1

100.9 ± 2.8
100.0 ± 1.6

100.9 ± 1.3
96.9 ± 0.7

98.9 ± 1.0
98.6 ± 0.9

103.1 ± 0.6
96.5 ± 2.0

107.5 ± 0.6
100.9 ± 1.3

109.6 ± 2.0
101.3 ± 1.1

Mean ± standard deviation (N = 6).
Containers were exposed to light.
c
Containers were protected from light using brown ultraviolet bags.
b

Results
During the study, all samples remained clear. However, there
was an increase in the yellow color of the solutions when
stored at 23ºC and ETL with the color appearing more intense
for the solution in vials probably due to the higher concentration. There was no color change for solutions stored at 5ºC
and PFL. For containers stored at 5ºC and PFL, there was a
slight pH change (≈0.7 units). The change in pH of solutions
stored at 23ºC with ETL was less (≈0.4 units).
Several new peaks appeared in acidic, alkaline, oxidized, and UV samples; however, none would interfere
with the parent or internal standard peaks (Figure 1). The
retention time of the internal standard was 11.1 minutes.
Heating the sample had the least effect on chemical stability only decreasing the concentration to 96.9% after 382
hours. Under acidic, alkaline, and oxidative conditions,
the initial concentration decreased to 85.4%, 75.6%, and
83.9%, respectively. Exposure of procainamide to UV light
caused a darkening in yellow color with time, and the concentration slowly decreased to 73.0% after 382 hours of
exposure. UV multiwavelength and spectral overlay analysis confirmed that the procainamide peak in all degradation
samples remained pure (≥99%).
The procainamide standard curve remained linear (R2 >
0.99) over the concentrations studied. Reproducibility of the
method over a 31-hour period was 0.6% while the interday
coefficients of variances were 1.5% (slope), 0.01% (linearity), and 1.8% (area ratio). The accuracy of the method was
99.0% ± 2.0%. The LOQ was determined to be 2 ng. All tailing factors were less than 2.
The mean results of the percent of initial concentration
remaining for all storage conditions and concentrations have
been summarized in Tables 1 and 2. The concentration of all

solutions remained above 94.6% when stored at either temperature for 193 days.

Discussion
All degradation samples produced faster eluting peaks with
some peaks being common between all the degradation solutions. The UV conditions caused the greatest degradation of
the procainamide. Acidic and oxidative conditions caused
much less degradation while exposure to alkaline conditions
caused the second most decrease in the initial concentration.
Heating the solution had the least effect of all the degradation
conditions.
The only stability data for procainamide diluted with NS2
reported that 100% of the drug was still present after 32
hours storage at room temperature. Because there was no
change in the concentration after 32 days, the first sample
selection time of 7 days was chosen as a responsible first
time period.
During the stability study, solutions stored at 23ºC and
ETL showed an increase in the darkening of the color; however, there was only a slight change in concentrations. The
increase in the concentration of the solution packaged in the
PVC bags after 28 days storage at 23ºC and ETL may have
been the result of loss of water from the bags under these
conditions as this is a known phenomenon.10 The effect was
not as apparent in the bags stored at 5ºC.
The manufacturer packages the commercial solution in
amber glass vials and several references11,12 recommend
protecting procainamide from light, so some changes in the
color could be expected over a short time period. According
to the manufacturer (Sandoz Canada Inc, oral communication, September 2012) and the American Hospital Formulary
System Drug Information,1 the solution is packaged under

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