Life cycles of inventions vary widely. Some inventions, like the hammer, prove to be useful for a variety of needs and stick around for millennia. Others, like the 8-track tape, wind up being useful for only a decade or so.
Fortunately for modern researchers, the mass spectrometer appears to be much more akin to the hammer than the 8-track tape. While the technology used to produce the modern mass spectrometer has advanced significantly in the past hundred years, the concept behind the tool itself has not changed, and we continue to discover new ways to apply it to our research.
The Importance of the Mass Spectrometer in DDD
As outlined in a Drug Discovery World article, use of the mass spectrometer in the drug discovery and development (DDD) process has been rich and varied. Many of the early efforts were associated with drug metabolism, pharmacokinetic, and pharmacodynamic studies. Twenty years ago, the focus was on using the mass spectrometer to characterize compounds from libraries, determine purity, and perform high-throughput screenings.
As a result of the success of efforts with proteomic and metabolomic profiling, all the major pharmaceutical companies purchased the latest mass spectrometers and developed a cadre of in-house technical experts.
More recently, the use of the extremely sensitive Accelerator-MS has meant that the in vivo metabolic distribution of a drug can be readily determined with minimal exposure levels of the radioactive compound.
The Importance of Truly Understanding the Mass Spectrometer
Researchers have predicted that even greater breakthroughs are just around the corner—and sometimes they’ve been right. It is critical, however, that researchers understand their tools, and this is as true of the mass spec as it is of other complex modern technologies. The tool is only useful in the hands of a trained operator. In DDD, for example, this means understanding that there is an inherent limitation in the mass spectrometer’s dynamic range, which can affect a differential sample analysis.
Fortunately, the pharmaceutical sector has learned valuable lessons and re-evaluated and refocused the role that the mass spectrometer plays in the DDD process. Just as a hammer is not useful to cut wood, it’s important to understand the limitations and capabilities of mass spec instrumentation, software, and firmware. For example, when using proteomic and metabolomic approaches, researchers must ask a specific biological question that requires a defined answer.
DDD professionals have realized that the mass spectrometer can continue to play a major role in certain areas of discovery and preclinical processes. They also now understand, however, that there is not much of a role for the MS to play in clinical development.
This is true in part because most of the research community applies different standards to the interpretation of data. Pharmaceutical companies, meanwhile, must ultimately satisfy stringent FDA regulatory requirements, and even MS/MS data analysis programs will not provide information that is completely accurate. There are ways to alleviate the shortcomings of the mass spectrometer, but this requires that researchers must be realistic in their expectations and practical in their decision-making processes.
Of course, the mass spectrometer is also only as good as the lab bench on which it sits. If the lab bench isn’t strong and stable enough, and doesn’t vent the hot air generated by its vacuum pumps, the mass spec could malfunction and one’s research would be made meaningless.
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