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Even through more sensitive methods for quantifying trace levels of curcumin in plasma were urgently needed, beyond tandem mass spectrometry, the Paul trap MS/MS/MS has never been tested for curcumin quantification. Because of its unique trap function to accumulate target compounds selectively by optimizing multiple stage MS experiments, it showed great potential to remove background issues reported at low concentration ranges. A novel Triple stage Ion Trap Mass Spectrometry coupled with High Performance Liquid Chromatography (HPLC-ITMS/MS/MS) method has been developed and validated as a curcumin quantification method, for the first time. The use of isotope labeled curcumin-d6 as a novel internal standard (IS) is suggested and tested according to FDA validation procedure. A simplified sample preparation is introduced and validated by coupling a novel acetonitrile precipitation with molecular weight cut-off size exclusion method. This method demonstrated excellent recovery rate of 96.69%-109.26% and minimum matrix effect of 95.40%-110.98%. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for curcumin in rat plasma were 0.1 ng/ml and 1 ng/ml respectively. The linear calibration curve for quantifying curcumin in rat plasma was 1-3000 ng/ml (r > 0.99) with intra-day and inter-day RSD and accuracy within ±5.11%. Its application in a Pharmacokinetics (PK) study demonstrated detection of curcumin at a very low plasma level (1.0 ng/ml) and it would be applied to larger sample size animal and clinical pharmacokinetic studies. The presented ITMS/MS/MS quantification method has shown its advantages, including better sensitivity, accuracy, precision, wider calibration range and simplicity in sample preparation, when comparing with other curcumin LC/MS analysis methods in the latest 4 years.

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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