Stability of Diluted Neuromuscular Blocking Agents Utilized in Perioperative Hypersensitivity Evaluation

Purpose: Neuromuscular blocking agents are a common cause of hypersensitivity reactions during surgery. An allergy evaluation, including skin testing of these drugs prior to future surgeries, may help prevent life threatening reactions. Drug concentrations utilized for skin testing vary by country and institution. The purpose of this study was to investigate the stored stability of clinically relevant dilutions of neuromuscular blocking agents (NMBAs), namely succinylcholine, atracurium, cisatracurium, rocuronium, pancuronium, and vecuronium, for skin prick/intradermal testing.

Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x, as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed for analysis, and compared to a freshly prepared set of reference dilutions.

Results: Acceptable potency of the stored preparations is defined as 90-110% of the initial drug concentration (versus a reference). All drugs were stable for at least 48 hours in the 1:10 dilution and for 24 hours in the 1:100 dilution. At higher dilution factors, the detectable amount of drug in the stored dilutions deteriorated rapidly, indicating that such preparations should be used immediately.

Conclusion: With increasing dilution factors, the stability of these drugs in saline decreases, increasing deviation between samples and references. The most stable dilutions for each of the drugs tested were 10x and 100x.