Stability of frozen methacholine solutions in unit-dose syringes for bronchoprovocation.
OBJECTIVE
Methacholine solutions < 0.25 mg/mL must be prepared fresh daily, while concentrations > or = 0.25 mg/mL must be prepared at 2-week intervals according to US Food and Drug Administration-required labeling. The purpose of this report was to determine whether freezing methacholine solutions in unit-dose syringes would allow less frequent preparation.


METHODS
Diluent containing 0.5% sodium chloride, 0.275% sodium bicarbonate, and 0.4% phenol was used to prepare 11 concentrations of methacholine ranging from 0.031 to 32.0 mg/mL. Three milliliters of each dilution was placed into 5-mL polypropylene syringes and immediately frozen. Methacholine concentrations were determined using a validated high-performance liquid chromatography assay after preparation (time zero) and at 0.5, 1, 1.5, 2, 3, 4, 5, and 6 months. On the day of analysis, the samples were allowed to thaw to room temperature. An additional set of each dilution was stored at room temperature for 24 h after thawing and then analyzed for methacholine.


RESULTS
Samples > or = 0.062 mg/mL analyzed immediately after thawing retained > or = 90% of labeled potency for at least 6 months, while the 0.031-mg/mL sample retained 90% potency for 4 months. Most samples analyzed 24 h after thawing lost potency.


CONCLUSIONS
If prepared and stored in unit-dose syringes frozen, methacholine solutions containing 0.062 to 32.0 mg/mL can be prepared at 6-month intervals, and solutions containing 0.031 mg/mL can be prepared at 4-month intervals. Once thawed, unused methacholine solutions should be discarded.
Asmus
Michael J
MJ
Department of Pharmacy Practice, College of Medicine, University of Florida, Gainesville, FL 32610-0486, USA. asmus@cop.ufl.edu
Vaughan
Leigh M
LM
Hill
Malcolm R
MR
Chesrown
Sarah E
SE
Hendeles
Leslie
L
D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D005615:Freezing; D006801:Humans; D016210:Methacholine Chloride / Q000737:chemistry*; D013594:Syringes
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride