Small Molecule Discovery
MS is also for small molecule discovery and quantitation. Chris Petucci, Ph.D., senior research scientist, analytical chemistry at Wyeth (www.wyeth.com), says his group uses MS to support medicinal chemistry and biological programs in drug discovery. MS is used to determine molecular weight, confirm the identity of compounds, and perform accurate mass analyses to determine molecular formulas of unknowns.
The Wyeth group uses tandem-MS to elucidate the structures of compounds and to quantitate trace levels of endogenous compounds in biological matrices such as steroids and fatty acids in serum and brain tissue. “This is an exciting area because the aim is to minimize compound attrition in the early stages of drug discovery,” states Dr. Petucci.
“Tandem-MS is the gold standard in the field of analytical chemistry for quantitating trace amounts of compounds down to the femtogram (10-15) level,” he explains. “It offers a degree of selectivity and specificity for quantitative studies because parent ions generated from a drug are fragmented into daughter ions. These are specific to the parent ion only and not to other molecules that could be present in the sample matrix.”
Important MS characteristics, says Dr. Petucci, include sensitivity, precision, and accuracy. “These are all important in quantitative studies, especially at the clinical stage, because there are FDA requirements for rugged and reproducible assays.” In addition, MS is versatile and rapid, providing the molecular weight for a compound in seconds, and when coupled with HPLC, it provides high levels of accuracy.