Hospital Pharmacy - April 2018 - 74

Hospital Pharmacy 53(2)

Table 1. Stability of Adenosine 2 mg/mL in 0.9% Sodium Chloride Injection Stored in Polyvinyl Chloride (PVC) and Polyolefin Infusion
Bags at Room Temperature (20°C-25°C) and Under Refrigeration (2°C-8°C) (n = 3).
Packaging type and storage
temperature
PVC bag at room temperature
PVC bag under refrigeration
Polyolefin bag at room
temperature
Polyolefin bag under refrigeration

% initial concentration remaining

Actual initial
concentration
(mg/mL)

1 day

3 days

7 days

14 days

1.959 ± 0.0011
1.964 ± 0.0019
2.008 ± 0.0004

99.0 ± 0.5
99.2 ± 0.6
98.5 ± 0.5

98.2 ± 0.1
97.1 ± 1.4
97.5 ± 0.4

102.3 ± 1.5
100.5 ± 2.1
101.3 ± 3.0

104.8 ± 0.4
102.4 ± 1.7
101.6 ± 0.9

1.981 ± 0.0031

99.7 ± 1.3

97.7 ± 0.7

102.8 ± 1.7

102.8 ± 0.4

Note. Data reported as mean of 3 samples under the same conditions ± standard deviation.

used as the drug source, and 0.9% Sodium Chloride Injection,
USP from Baxter (NDC# 0338-0049-38, Lot# P332106) was
used as the diluent. Sterile empty polyolefin bags (50-mL
capacity) were obtained from Baxter (Product# 2B8019,
Lot# UR15E27088). Sterile empty PVC bags were not available commercially; therefore, 50-mL PVC bags of 0.9%
Sodium Chloride Injection, USP (Baxter, NDC# 0338-004931, Lot# P329979) were drained completely through the
medication port before the filling of stability samples. To
ensure a uniform starting concentration of all stability samples, a batch of 2 mg/mL adenosine solution was prepared by
diluting 390 mL source adenosine solution with 195 mL diluent in a 1-L glass beaker. About 8% volume overage was
included for the batch size to account for any potential loss of
transfers. The 2 mg/mL adenosine solution was then packaged and sealed into the empty PVC and polyolefin bags, 45
mL each. These stability samples were prepared in triplicate
for each bag type and storage temperature (a total of 12 samples). Five standard solutions were prepared from adenosine
powder (Acros Organics, lot# A0263503) in deionized water.
The standards were used to build a calibration curve and replicate samples were frozen on the first day. A set of standards
was thawed prior to high-performance liquid chromatography (HPLC) analysis each day of the study.
The infusion bag samples were assessed for stability immediately after preparation and after 1 day, 3 days, 7 days, and 14
days. At each time point, the infusion bags were first visually
inspected against a light background for color change, clarity,
and particulates. A 1-mL aliquot was withdrawn from each bag
using aseptic compounding technique. The bags were then
resealed and returned to their respective storage conditions. For
each aliquot sample, 0.1 mL was accurately transferred and
diluted with 0.9 mL purified water for HPLC analysis.2,3 The
pH of the remaining aliquot sample was measured and recorded.

Results and Discussion
At time zero, the 2 mg/mL adenosine solution in both bag
types appeared clear, colorless, and free of particulates. The
pH values of the samples ranged from 6.1 to 6.7. Over 14
days of storage at room temperature or refrigeration, no

considerable change in visual appearance or pH was observed
in any bags. Based on the HPLC analysis results shown in Table
1, all samples retained 90% to 110% of the initial drug concentration. No significant degradation peaks were observed
in the HPLC chromatograms.

Conclusion
Adenosine solutions of 2 mg/mL in 0.9% Sodium Chloride
Injection, USP stored in 50-mL PVC and polyolefin infusion
bags were physically and chemically stable for up to 14 days
at room temperature or under refrigeration. Two important
reminders must be made for the sterile compounding of adenosine IV bags for use in patients. First, 50-mL bags of 0.9%
Sodium Chloride Injection, USP often contain >10% overfill. To obtain an accurate final drug concentration, it is recommended to withdraw the overfill volume prior to the
addition of drug source solution. Second, pertinent USP
⟨797⟩ requirements must be followed to minimize microbial
contamination during compounding.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

References
1.

Henzlova MJ, Duvall WL, Einstein AJ, Travin MI, Verberne
HJ. ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers. J Nucl Cardiol.
2016;23(3):60639.
2. Kaltenbach M, Hutchinson DJ, Bollinger JE, Zhao F. Stability
of diluted adenosine solutions in polyvinyl chloride infusion
bags. Am J Health Syst Pharm. 2011;68:1533-1536.
3. Almagambetova E, Hutchinson D, Blais DM, Hutchinson
D, Zhao F. Stability of diluted adenosine solutions in polyolefin infusion bags. Hosp Pharm. 2013;48(6):484-488.

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