July 3, 2020

Strathmann FG, Lynch KL, Krotulski AJ, Negri P, Cichelli J, Meyer MR

Clinical Chemstry

High Resolution Mass Spectrometry (HRMS) has allowed mass spectrometrists the capability to exchange nominal mass measurements for accurate mass measurements. Integration of a collision cell extends this capability with fragmentation providing high mass accuracy detection of precursor fragments with library matching for identification. Add to that the ability to digitally store an entire sample and to retrospectively reanalyze for new compounds not originally considered during the initial analysis. And finally, incorporate the ability to detect a compound by HRMS and then trigger fragmentation as a secondary layer of identification during a single analytical run.

With all these capabilities, it is easy to see why HRMS may have been poised at one time to virtually eliminate conventional quadrupole-based mass spectrometry. Anyone who has been in laboratory medicine in the era of clinical mass spectrometry has likely watched or participated in a debate among laboratorians regarding quadrupole versus HRMS and which to pursue, made a physical or mental list of the pros and cons of each while deciding which to purchase, and been part of the successful or not so successful implementation of one or both types of technology. HRMS has been at the forefront of the opioid crisis internationally and continues its dominance in providing much needed insight for all classes of designer drugs.

The origin of designer drugs is considerably older than the technology being used to combat them, and their popularity has been based on their physiological ability to mimic existing illegal and legal drugs in addition to the inability for laboratories to detect them reliably. Currently overshadowed by the COVID-19 pandemic, the opioid crisis continues, and many laboratorians continue their collective fight, though unfortunately even further out of the spotlight. The expertise of laboratorians, public health, and law enforcement, blended with the expertise of mass spectrometrists using HRMS, has proven to be an effective, team-based approach to staying ahead of the continuous evolution of designer drugs.

In this Q&A, five experts discuss the strengths, challenges, and limitations of using HRMS for designer drug identification. These scientists also serve as an example of the diverse backgrounds being leveraged in this critical private and public partnership between mass spectrometry vendors, profit and nonprofit organizations, and academic institutions around the world.
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