Evaluating Degradation with Fragment Formation of Prehospital Succinylcholine by Mass Spectrometry

Abstract

Objectives: Pharmaceutical manufacturers recommend refrigerating succinylcholine at a temperature range of 2-8°C. With widespread use of prehospital succinylcholine on ambulances without refrigeration, it is important to understand the stability of this drug. Using mass spectrometry, this study investigated the degradation of the succinylcholine compound before and after its exposure to ambulance cabin temperatures, while removing light exposure. A 10% degradation threshold was set as not appropriate for human use, in accordance with U.S. Food and Drug Administration guidelines. Methods:The study used 17 vials of succinylcholine sealed with duct tape in light-resistant bags. The bags were placed in climate controlled compartments in two ambulances: one stationed in a garage and the other stationed outdoors. Mass spectrometry analysis was used to examine drug degradation at Time 0, the 14th day of the first month, and monthly from Time 0 to 7 months.Results: The degradation products of succinyl monocholine (SMC) and choline are already present at Day 0. Ten percent degradation was achieved at approximately 90 days into the experiment. Temperature in the ambulance climate controlled compartment was 70°F, with a range from 56 to 89°F during the 6-month time period.Conclusions: Identifiable breakdown fragments of succinylcholine have been identified using mass spectrometry with fresh drug upon receipt from the manufacturer. Ten percent degradation was not observed until approximately 90 days after being placed on ambulances. Temperature variations did not significantly contribute to degradation of succinylcholine, and it is safe for injection until approximately 90 days in similar climates. ACADEMIC EMERGENCY MEDICINE 2010; 17:631-637 ª 2010 by the Society for Academic Emergency MedicineKeywords: succinylcholine, mass spectrometry, degradation, temperature S uccinylcholine is a depolarizing neuromuscular blocking agent used to assist endotracheal intubation. Previous degradation studies apply to the hospital setting, where succinylcholine is stored at the recommended temperature. However, in the prehospital setting, no current literature exists involving succinylcholine degradation and fragment formation as measured by mass spectrometry.It is essential to understand the factors that can lead to degradation of the drug. It is estimated that 85% of succinylcholine is destroyed within the 30 seconds of injection into the blood, and only 5% remains present 2 minutes after injection.1 Studies have shown that the drug is susceptible to a loss of potency with increases in temperature and light and decreases in pH.2-5 While light affects the stability of succinylcholine injections ª

Application of hydrophilic interaction liquid chromatography for the quantification of succinylcholine in Active Pharmaceutical Ingredient and medicinal product. Identification of new impurities of succinylcholine chloride

“…Identified impurities have never before been revealed in API or in the medicinal product referred to as SCh, even with the application of mass spectrometry for identifying an active substance [1, 8, 16, 17]. It needs to be pointed out that a fragmentary spectrum of SCh is completely compatible with data in the literature, which means that the observed mass is a double-charged ion, and the results of its fragmentation are the formation of both single- and double-charged fragments [16, 17]. Upon the basis of, among others, the mechanism of ionization of the fragmentation of SCh, the identification of unknown compounds visible in Fig.…”

“…For that reason, a number of analytical methods were developed, for impurities and active substance assay in API or in pharmaceutical formulations. For the separation and quantification impurities and SCh, the following have been applied: ion pair chromatography applying a different a counter couple and electrochemical or conductometric detection [9, 10, 11, 12], liquid chromatography in the system of reversed phases with fluorescence detection [13], UV [14], capillary electrophoresis [15], liquid chromatography combined with mass spectrometry [1, 16, 17] and gas chromatography [8]. The majority of the methods described in the available literature are based on reversed phase liquid chromatography with or without the application of ion pair.…”