(Georgia Institute of Technology, 2007-12-17)
Johnson, Kristin R.
The counterfeiting of pharmaceuticals, especially antimalarials, is a well-recognized and growing public health problem. There have been an alarming number of reports of counterfeit antimalarials throughout the world and insufficient regulations and xactivity. Thus there is an urgent need for a rapid and sensitive authentication and screening tool for multiple antimalarials. While many methods have been developed using HPLC, MS, or LC-MS to screen individual antimalarials, no methods are available for the analysis of multiple antimalarial drugs within a single run. In this study, Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM) was used as a selective and rapid way to screen ten common antimalarials. The compounds were first individually analyzed using electrospray ionization mass-spectrometry (ESI-MS). Following this, a corresponding MS/MS spectrum was obtained to enable selection of the optimal unimolecular decay fragmentation ( transition ) of each antimalarial. Finally, these single reaction monitoring (SRM) transitions were combined into a method that utilizes HPLC separation followed by multiple reaction monitoring (MRM) in an ion trap mass analyzer allowing for sequential screening of a mixture of these compounds within a single LC-MS/MS run. This method has both pharmaceutical and medical applications with the capability of providing drug quality control measurements and the detection of many drugs and their metabolites in biological samples.