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Figure 1. Cardioplegia solution label.

results were ultimately filed with the respective compounding records and retained for 2 years per departmental policy.
The 30 bags of cardioplegia were only released if all 3 lab
samples reported a potassium concentration within ±5% of
the expected value (ie, 26 mEq/L). If any of the laboratory
results were outside this margin of tolerance, the batch would
not be released and the suspect bags would be resampled and
retested to rule out any laboratory error. If the results were
still out of range, a new batch of cardioplegia solutions would
be compounded and tested according to the exact same procedure. To date, all batches of cardioplegia using this process
have been within the desired range for weight, volume, and
potassium content, and it has not been necessary to reject a
production batch.
Once all protocolled QC tests have been completed, a
final product label (Figure 1) was placed on each bag of cardioplegia, making sure that neither the incremental volume
marking on the bag nor the Abacus bag label was obscured.
Only the original expiration date/time generated by the
Abacus bag label was covered by the new label. In addition,
"refrigerate" and "cardioplegia solution" auxiliary labels
were also affixed to each bag. A beyond use date of 9 days
was assigned to each batch of dNCS, with a labeled expiration date of 7 days to account for the usual quarantine time
prior to release per our production standard.

Stability Testing
Stability testing was performed per USP 797 guidance documents regarding stability testing.10,11 Stock dNCS bags were
obtained from the Pharmacy Department at Boston Children's
Hospital, as they were regularly compounded for clinical
use. Over a 6 month period, 4 different lots of dNCS, and 4
bags from each lot, were assayed. Given that stability data

Hospital Pharmacy 52(11)
are lacking for several of the additives in dNCS, this study
was conducted at different environmental conditions to
establish an evidence-based shelf-life. Each dNCS bag was
assessed for physical and chemical stability under 3 different
environments, ie, refrigerated at 4°C, at 35°C in an incubator, and at 70°C under 80% relative humidity in an environmental chamber. A light exposure arm was also set up at
25°C under 150 lumens, paired with a similar sample in the
dark at the same temperature.
The Plasma-Lyte A 7.4 (Baxter Healthcare Corporation,
Deerfield, Illinois) solution used in dNCS contains no antimicrobials and is adjusted with sodium hydroxide by the
manufacturer to a pH of 7.4 (reported range, 6.5-8.0). The
electrolyte content of the salt components per 100 mL is as
follows: 526 mg sodium chloride, 502 mg sodium gluconate,
368 mg sodium acetate trihydrate, 37 mg potassium chloride,
and 30 mg magnesium chloride. Total ionic concentrations
are 140 mEq/L sodium, 5 mEq/L potassium, 3 mEq/L magnesium, and 98 mEq/L chloride. For the purpose of this
chemical stability testing, lidocaine, mannitol, and gluconate
concentrations were monitored over time.
Using a 1-mL syringe, 1 mL of dNCS sample was drawn
at each sampling time from the original bag and transferred
to a 1.5-mL snap cap polypropylene Eppendorf centrifuge
tube. Immediately after, 100 µL of that dNCS sample were
taken and diluted with 900 µL of pure milliQ water; 10µL of
the diluted solution were mixed with 10µL of internal standard (IS) at 1 mg/mL and diluted with 980 µL of pure milliQ
water in a 1.5-mL screw cap amber glass injection vial to be
loaded onto the liquid chromatography (LC) sample tray for
injection. Freshly made calibrators and QC samples were run
in the same sequence with the unknown samples to construct
a calibration curve and establish the accuracy of the results.

Liquid Chromatography
An Agilent 1200 series high-performance liquid chromatography system (Agilent Technologies, Wilmington, Delaware)
was used, consisting of a degasser, a binary pump, an injector/autosampler, a column heater, and a cooled thermostat
controlled at 4°C autosampler compartment. Separation was
performed using an Agilent Zorbax SB-C18, 4.6 × 150 mm
(5 µm) column equipped with a Phenomenex SecurityGuard
analytical guard column. Both were maintained to 38°C
throughout the entire analysis, eluted with a mobile phase of
50% v/v pure milliQ water with 0.1% v/v formic acid
CovaChem (Sigma-Aldrich, St Louis, Missouri), and 50%
v/v methanol Lichrosolv (Sigma-Aldrich, St Louis,
Missouri). Bupivacaine was used as the IS (Sigma-Aldrich,
St Louis, Missouri). The flow rate was set at 1 mL/min, and
the injection volume was 10 µL after needle washing with
acetonitrile. The duration of each run was 4 minutes.
The chromatographic separation method was validated
for 3 components of the dNCS, ie, lidocaine, mannitol, and
sodium gluconate. Spiked calibrators and QC samples were

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