How do you catch the next designer drug? With a library, of course.

As I have mentioned in my previous posts, more and more drug overdose cases involve novel psychoactive substances (NPS) which are several-fold more potent than their traditional illicit counterparts and are difficult to detect with routine drug testing. Cryptic and sometimes unpronounceable names such as U-47700, PB-22, AMB-FUBINACA, Krokodil, and Black Mamba are some of the most dangerous drugs you’ve never heard of. They are responsible for psychosis, seizures, coma and death. NPS or “designer drugs”, almost by definition, are made of chemical combinations we haven’t seen before. They almost never match traditional databases. When forensic toxicologists come upon a case with clear signs involving drug overdose but tests come back negative for the usual suspects of opiates, cocaine, amphetamines, who do they call for a second opinion? How do they identify the substances causing the issues?

What separates many NPS from traditional drugs of abuse are the rapid introduction of newer versions or analogues which can evade detection and have increased “highs.” Clandestine chemists tweak the structures of these molecules using techniques similar to those employed in the pharmaceutical industry. These alterations may include new chemical structures or subtle changes such as a single substituted hydrogen atom. Tiny structural differences can cause big detection challenges, especially with established immunoassays which rely on detecting particular structures. While tandem mass spectrometry (MS/MS) or gas chromatography (GC-MS) work well enough for detecting substances on a pre-determined list of compounds, their coverage is only as good as the latest spectral library or compound database.

Samples with negative results from conventional drug screening but are suspected to have NPS require further investigation to identify these “unknowns.” Many NPS are relatively new on the street, over five hundred have been identified as new designer drugs in the previous five years. In a collective effort, law enforcement agencies and forensic labs are using innovative MS technologies for faster identification of new designer drugs and predicting the next NPS.

Forensic toxicologists such as Dr. Giampietro Frison are successfully applying high-resolution accurate mass MS (HRAM MS) for general screening of unknowns and identifying new designer drugs in blood, urine and hair. The Frison lab at LIATF in Venice, Italy utilizes the Thermo Scientific™ Q Exactive™ Focus Hybrid Quadrupole-Orbitrap MS which has exceptional mass accuracy, better than 1-2 parts per million (ppm). They are able to build spectral libraries that accurately distinguish between closely related NPS that could not otherwise be resolved by MS/MS. Orbitrap-based MS also allows them to retrospectively analyze data without re-running samples for faster identification of new NPS.

Roy Gerona from the University of California, San Francisco (UCSF) specializes in identifying and classifying synthetic cannabinoids, one of the largest and fastest growing categories of designer drugs. His work involves synthesizing potentially new NPS reference standards, from “prophetic structures.” Essentially, Dr. Gerona is using a similar approach as the underground chemists, making small changes to existing NPS molecules in order to predict future synthetic cannabinoids. So far, his group has made over 150 potential synthetic cannabinoids and metabolites for reference libraries. Software tools such as Thermo Scientific™ Compound Discoverer™ can also help with identifying new molecules that match with common substructures.

Innovations in MS hardware and software along with dedicated scientists such as Dr. Frison and Dr. Gerona are all helping to build better libraries and databases to overcome the challenges of catching the next designer drugs.


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Source: by Dominic Andrada

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