A report on this research – funded by the Society of Analytical Chemists of Pittsburgh and the Wellcome Trust of Great Britain -- will be published this summer in the journal ChemMedChem.
Georgia Tech Assistant Professor of Chemistry and Biochemistry Facundo Fernandez began studying counterfeit anti-malarials two years ago using conventional analytical chemistry techniques based on liquid chromatography and mass spectrometry. But these methods required more than two hours to analyze just one sample. So he and his graduate students developed new, high-throughput ionization techniques that now allow them to complete the same analytical analyses in just five seconds per sample.
"This is a new generation of techniques in mass spectrometry," Fernandez said. "We don't probe our samples under vacuum like you normally do with mass spectrometry. We can hold a solid sample under atmospheric pressure and use one of our new tools to ionize its surface components. The ionized particles are subsequently analyzed by mass spectrometry. This method eliminates the time and costs associated with sample preparation."
Specifically, Fernandez and his students have worked to improve two recently developed analytical chemistry techniques – desorption electrospray ionization (DESI) developed by Purdue University and direct analysis in real time (DART) developed by the Japanese company JEOL.
The researchers use DESI to screen anti-malarials to quantify the amount of the active ingredient artesunate in counterfeits. In DESI, researchers use a high-speed, charged spray containing alcohol and water. Typically, this solvent mixture reacts with a solid sample, such as a tablet, picking up molecules from its surface and transferring them to a detector.
But artesunate is a relatively unstable molecule that fragments easily and causes DESI to lose its sensitivity. So Fernandez and his students have now added an alkylamine compound to the alcohol-water mixture to form a stable molecular species, preventing artesunate fragmentation and thereby increasing sensitivity. They call this process "reactive DESI."
DART, on the other hand, involves an ionizing beam of marginally stable helium atoms generated by an electric discharge. The DART ionization mechanism is still not completely understood. In ongoing research, Fernandez and his students are working to interface DART with other instruments to help understand the chemistry behind the methodology.
To date, they have interfaced DART with a mass spectrometer, but the latter is typically too bulky and expensive to use in a field setting. So researchers plan to interface DART with a similar instrument called an ion mobility spectrometer (IMS), which is used in airports to detect explosives. They hope the pair of techniques could be used in the field to screen solid samples of anti-malarial drugs.
"Our findings not only demonstrate the usefulness of DART for rapid screening of counterfeit drugs, but also have unprecedented implications for malaria control," Fernandez and his co-authors report in ChemMedChem. "We foresee that both DART and DESI will have a tremendous impact in a variety of scientific fields, ranging from drug quality control, screening and discovery to biological applications, such as metabonomics and/or proteomics."
Technical Contact: Facundo Fernandez, Georgia Tech (404-385-4432); E-mail: (firstname.lastname@example.org)
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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