Detection of deferoxamine using liquid chromatography/mass spectrometry with electrospray ionization [poster]
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Intranasally administered deferoxamine (DFO) is being developed by our laboratory for the treatment of several neurodegenerative diseases. A big weakness as we try to obtain FDA-approval for clinical trials is the lack of pharmacokinetic data due to the absence of a method to quantify DFO. In this study, we will first develop a method to quantify DFO using liquid chromatography/mass spectrometry (LC/MS), which can detect compounds with very high sensitivity and specificity, and then use it to answer questions about drug distribution in a rat model. Thus far, manual injections of DFO into the LCQ1 ion trap MS with electrospray ionization (Thermo Scientific, West Palm Beach, FL), have shown that even without optimization, the instrument can detect DFO at incredibly low concentrations (0.5 pg). Further, DFO yields a specific ionization pattern that can allow it to be properly identified in complex matrices like homogenized animal tissue. Similar analysis combining LC/MS using a QTRAP 5500 (AB Sciex, Framingham, MA), a more advanced model that uses multiple reaction monitoring, has also shown a retention time of 3.3 min, a molecular ion at 561.3 m/z, and specific fragments at 201, 242, 319, and 361 m/z. Given the success thus far with the initial experiments, it seems likely that LC/MS will be a great method to quantify DFO and allow us to answer basic pharmacokinetic questions in rat tissue, furthering our cause to get this drug to market for treating patients with neurodegenerative disease.