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Easier-to-use devices, like the Waters ACQUITY QDa detector, expand the use of mass spec- trometry in the pharmaceutical sciences. (Image courtesy of Waters.)
Other factors come into play. “These instru- ments may then be further characterized by whether they are capable of measuring only mass or if they can isolate an ion of particular mass-to-charge ratio, and then fragment it prior to mass determination,” Josephs explains. The latter is tandem mass spectrometry, and this form of accurate MS is required to eluci- date structures.
The Thermo Scientifi c Orbitrap mass analyzer observes “the image current created by the oscillation of ions accelerated into and trapped by an electrostatic fi eld,” says Josephs, adding that the Orbitrap Fusion Lumos tribrid mass spectrometer produces very high-resolution accurate mass (HRAM) spectra and off ers multi- ple modes of tandem mass spectrometry. Such confi gurations, he points out, “are very power- ful for structural elucidation of unknowns and for peptide sequencing, and have become the gold standard in the industry for these appli- cations…. The advent of HRAM has simplifi ed the automated assignments of structures and metabolic soft spots, greatly increasing the throughput of these assays.”
Expanding utility MS shows increasing applications in disease-
related research. Scientists from Merck (Rahway, N.J.), Kings College (London, England) and Waters tested the ACQUITY QDa MS platform
in drug discovery and development and re- ported: “Overall, the compact mass detector has proven to be a valuable and reliable mass detection and compound confi rmation tool for the open access environment in the phar- maceutical discovery and development space where speed and uptime are crucial, unit mass resolution is a necessity and sample availability is rarely a concern.” They added, “The benefi ts of the compact mass detector for use in a wide variety of applications including standard small molecule analysis [high-throughput screening] and QC type analyses, as well as biological samples and quantitation studies have been demonstrated” (Gao, J. et al. Journal of Pharmaceutical and Biomedical Analysis; Jan. 2016, doi:10.1016/
j.jpba.2016.01.017).
An October 2015 article in Antimicrobial Agents and Chemotherapy (Page-Sharp, M. et al., doi:10.1128/AAC.01740-15) reports on the use of dried blood spots in antibiotic assays analyzed with liquid chromatography followed by tandem MS. The researchers concluded that this technique could be used to determine a drug’s pharmacokinetics (how the drug aff ects the body) and pharmacodynamics (how the body aff ects the drug).
Metabolomics-based MS and gas and liquid chromatography were used to analyze the phenotypes of four cancer cell lines—two from colon cancer and two from ovarian cancer. Halama et al., writing in a July 2015 article in the Journal of Translational Medicine (doi: 10.1186/ s12967-015-0576-z), said, “Our study provides a panel of distinct metabolic fi ngerprints be- tween colon and ovarian cancer cell lines. These may serve as potential drug targets, and now can be evaluated further in primary cells, biofl u- ids and tissue samples for biomarker purposes.”
As the pharmaceutical industry continues its search for critical targets and develops ever- more sophisticated compounds, MS will make it possible for researchers to look at increasingly fi ner levels of molecular detail.
Mike May is a freelance writer and editor living in Ohio. He can be reached at mikemay1959@
gmail.com.
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