Rapid identification of new or emerging psychoactive substances remains a critical challenge in f... more Rapid identification of new or emerging psychoactive substances remains a critical challenge in forensic drug chemistry laboratories. Current analytical protocols are well-designed for confirmation of known substances yet struggle when new compounds are encountered. Many laboratories initially attempt to classify new compounds using gas chromatography mass spectrometry (GC-MS) data. Though there is a large body of research focused on analysis of illicit substances with GC-MS, there is little high-level discussion of mass spectral trends for different classes of drugs. This manuscript compiles literature information and performs simple exploratory analyses on evaluated GC-MS data to investigate trends of electron ionization (EI) mass spectra on the most reported illicit substance classes. Additionally, this work offers other important aspects: brief discussions of how each class of drugs is used; descriptions of proposed fragmentation pathways of commonly observed ions in EI-MS data; and summaries of mass spectral trends that can help an analyst classify new illicit compounds.
<p>(a) Schematic overview of biochemical and physical sub-processes considered in the compu... more <p>(a) Schematic overview of biochemical and physical sub-processes considered in the compuGUT. (b) 5-step model of anaerobic digestion, adapted from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145309#pone.0145309.ref018" target="_blank">18</a>]. Biomass functional group active in each step indicated in parentheses. (c) Summary of component exchange processes. Material in the lumen environment is transported along the length of the colon where as mucus material is stationary along the length of the colon and only experiences axial transport.</p
Identifying mixture components is a well-known challenge in analytical chemistry. The Inverted Li... more Identifying mixture components is a well-known challenge in analytical chemistry. The Inverted Library Search Algorithm (ILSA) is a recently proposed method for identifying mixture components using in-source collision induced dissociation (is-CID) mass spectra of a query mixture and a reference library of pure compound is-CID mass spectra (J. Am. Soc. Mass Spectrom. 2021, 32, 7, 1725–1734). This article presents several subtle but important advances to the algorithm, including updated compound matching strategies that improve result explainability, and spectral filtering to better handle noisy mass spectra as is often observed with real-world samples such as seized drug evidence.
Using an ADM-Based Model to Explore Human Intestinal Flora Behaviour Arun S. Moorthy University o... more Using an ADM-Based Model to Explore Human Intestinal Flora Behaviour Arun S. Moorthy University of Guelph,2011 Advisor Professor Hermann J. Eberl The human colon is an anaerobic environment densely populated with bacterial species, creating what is known as the human intestinal microbiome; an ecosystem imperative to physiological function with regards to metabolism of non-digestible residues, growth of cells and immune protection from invading organisms. As such, quantifying, and subsequently developing an understanding of the behaviour of this microbial population can be of great value. Unfortunately, because of the physical inaccessibility of many parts of the gastro-intestinal (GI) tract, routine experimentation with this environment is not practical. However, theoretical modelling techniques including in vitro and in silico simulation/experimental platforms provide a means by which further studying of intestinal microflora can be approached. Perfecting these theoretical models i...
Synthesis, distribution and abuse of fentanyl, a synthetic opioid, has led to a critical worldwid... more Synthesis, distribution and abuse of fentanyl, a synthetic opioid, has led to a critical worldwide epidemic. Mass spectral library searching for opioids remains unresolved despite being central to law-enforcement involving identification, monitoring and prosecution of opioid related crimes. In this article, two model problems are presented to illustrate difficulties associated with fentanyl identification. A collection of both currently-employed similarity measures and intuitive measures of dissimilarity are employed to simulate identifying fentanyl analogs with mass spectral library searching.
A method for the targeted confirmation of synthetic opioids and related compounds observed in for... more A method for the targeted confirmation of synthetic opioids and related compounds observed in forensic seized drug analysis was developed and evaluated. Investigated settings included column type, flow rate, temperature program, inlet temperature, source temperature, and tune type. It was evaluated against a suite of 222 synthetic opioids and related compounds, and successfully differentiated all but four compound pairs based on retention time or mass spectra. Compared to a general confirmatory method, the targeted method was up to 25 times more sensitive and provided at least a two-fold increase in retention time differences. Analysis of case extracts successfully demonstrated utility of the method and showed no instance of carryover, although the high polarity column required wider retention time windows than other columns.
Journal of the American Society for Mass Spectrometry
This manuscript introduces a new library-search algorithm for identifying components of a mixture... more This manuscript introduces a new library-search algorithm for identifying components of a mixture using in-source collision-induced dissociation (is-CID) mass spectra. The two-stage search, titled the Inverted Library-Search Algorithm (ILSA), identifies potential components in a mixture by first searching its low fragmentation mass spectrum for target peaks, assuming these peaks are protonated molecules, and then scoring each target peak with possible library matches using one of two schemes. Utility of the ILSA is demonstrated through several example searches of model mixtures of acetyl fentanyl, benzyl fentanyl, amphetamine and methamphetamine searched against a small library of select compounds and the NIST DART-MS Forensics library. Discussion of the search results and several open areas of research to further extend the method are provided. A prototype implementation of the ILSA is available at https://github.com/asm3-nist/DART-MS-DST.
This manuscript outlines a straightforward procedure for generating a map of similarity between s... more This manuscript outlines a straightforward procedure for generating a map of similarity between spectra of a set. When applied to a reference set of spectra for Type I fentanyl analogs (molecules differing from fentanyl by a single modification), the map illuminates clustering that is applicable to automated structure assignment of unidentified molecules. An open-source software implementation that generates mass spectral similarity mappings of unknowns against a library of Type I fentanyl analog spectra is available at http://github.com/asm3nist/FentanylClassifier.
A mass spectral library search algorithm that identifies compounds that differ from library compo... more A mass spectral library search algorithm that identifies compounds that differ from library compounds by a single "inert" structural component is described. This algorithm, the Hybrid Similarity Search, generates a similarity score based on matching both fragment ions and neutral losses. It employs the parameter DeltaMass, defined as the mass difference between query and library compounds, to shift neutral loss peaks in the library spectrum to match corresponding neutral loss peaks in the query spectrum. When the spectra being compared differ by a single structural feature, these matching neutral loss peaks should contain that structural feature. This method extends the scope of the library to include spectra of "nearest-neighbor" compounds that differ from library compounds by a single chemical moiety. Additionally, determination of the structural origin of the shifted peaks can aid in the determination of the chemical structure and fragmentation mechanism of th...
Rapid identification of new or emerging psychoactive substances remains a critical challenge in f... more Rapid identification of new or emerging psychoactive substances remains a critical challenge in forensic drug chemistry laboratories. Current analytical protocols are well-designed for confirmation of known substances yet struggle when new compounds are encountered. Many laboratories initially attempt to classify new compounds using gas chromatography mass spectrometry (GC-MS) data. Though there is a large body of research focused on analysis of illicit substances with GC-MS, there is little high-level discussion of mass spectral trends for different classes of drugs. This manuscript compiles literature information and performs simple exploratory analyses on evaluated GC-MS data to investigate trends of electron ionization (EI) mass spectra on the most reported illicit substance classes. Additionally, this work offers other important aspects: brief discussions of how each class of drugs is used; descriptions of proposed fragmentation pathways of commonly observed ions in EI-MS data; and summaries of mass spectral trends that can help an analyst classify new illicit compounds.
<p>(a) Schematic overview of biochemical and physical sub-processes considered in the compu... more <p>(a) Schematic overview of biochemical and physical sub-processes considered in the compuGUT. (b) 5-step model of anaerobic digestion, adapted from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145309#pone.0145309.ref018" target="_blank">18</a>]. Biomass functional group active in each step indicated in parentheses. (c) Summary of component exchange processes. Material in the lumen environment is transported along the length of the colon where as mucus material is stationary along the length of the colon and only experiences axial transport.</p
Identifying mixture components is a well-known challenge in analytical chemistry. The Inverted Li... more Identifying mixture components is a well-known challenge in analytical chemistry. The Inverted Library Search Algorithm (ILSA) is a recently proposed method for identifying mixture components using in-source collision induced dissociation (is-CID) mass spectra of a query mixture and a reference library of pure compound is-CID mass spectra (J. Am. Soc. Mass Spectrom. 2021, 32, 7, 1725–1734). This article presents several subtle but important advances to the algorithm, including updated compound matching strategies that improve result explainability, and spectral filtering to better handle noisy mass spectra as is often observed with real-world samples such as seized drug evidence.
Using an ADM-Based Model to Explore Human Intestinal Flora Behaviour Arun S. Moorthy University o... more Using an ADM-Based Model to Explore Human Intestinal Flora Behaviour Arun S. Moorthy University of Guelph,2011 Advisor Professor Hermann J. Eberl The human colon is an anaerobic environment densely populated with bacterial species, creating what is known as the human intestinal microbiome; an ecosystem imperative to physiological function with regards to metabolism of non-digestible residues, growth of cells and immune protection from invading organisms. As such, quantifying, and subsequently developing an understanding of the behaviour of this microbial population can be of great value. Unfortunately, because of the physical inaccessibility of many parts of the gastro-intestinal (GI) tract, routine experimentation with this environment is not practical. However, theoretical modelling techniques including in vitro and in silico simulation/experimental platforms provide a means by which further studying of intestinal microflora can be approached. Perfecting these theoretical models i...
Synthesis, distribution and abuse of fentanyl, a synthetic opioid, has led to a critical worldwid... more Synthesis, distribution and abuse of fentanyl, a synthetic opioid, has led to a critical worldwide epidemic. Mass spectral library searching for opioids remains unresolved despite being central to law-enforcement involving identification, monitoring and prosecution of opioid related crimes. In this article, two model problems are presented to illustrate difficulties associated with fentanyl identification. A collection of both currently-employed similarity measures and intuitive measures of dissimilarity are employed to simulate identifying fentanyl analogs with mass spectral library searching.
A method for the targeted confirmation of synthetic opioids and related compounds observed in for... more A method for the targeted confirmation of synthetic opioids and related compounds observed in forensic seized drug analysis was developed and evaluated. Investigated settings included column type, flow rate, temperature program, inlet temperature, source temperature, and tune type. It was evaluated against a suite of 222 synthetic opioids and related compounds, and successfully differentiated all but four compound pairs based on retention time or mass spectra. Compared to a general confirmatory method, the targeted method was up to 25 times more sensitive and provided at least a two-fold increase in retention time differences. Analysis of case extracts successfully demonstrated utility of the method and showed no instance of carryover, although the high polarity column required wider retention time windows than other columns.
Journal of the American Society for Mass Spectrometry
This manuscript introduces a new library-search algorithm for identifying components of a mixture... more This manuscript introduces a new library-search algorithm for identifying components of a mixture using in-source collision-induced dissociation (is-CID) mass spectra. The two-stage search, titled the Inverted Library-Search Algorithm (ILSA), identifies potential components in a mixture by first searching its low fragmentation mass spectrum for target peaks, assuming these peaks are protonated molecules, and then scoring each target peak with possible library matches using one of two schemes. Utility of the ILSA is demonstrated through several example searches of model mixtures of acetyl fentanyl, benzyl fentanyl, amphetamine and methamphetamine searched against a small library of select compounds and the NIST DART-MS Forensics library. Discussion of the search results and several open areas of research to further extend the method are provided. A prototype implementation of the ILSA is available at https://github.com/asm3-nist/DART-MS-DST.
This manuscript outlines a straightforward procedure for generating a map of similarity between s... more This manuscript outlines a straightforward procedure for generating a map of similarity between spectra of a set. When applied to a reference set of spectra for Type I fentanyl analogs (molecules differing from fentanyl by a single modification), the map illuminates clustering that is applicable to automated structure assignment of unidentified molecules. An open-source software implementation that generates mass spectral similarity mappings of unknowns against a library of Type I fentanyl analog spectra is available at http://github.com/asm3nist/FentanylClassifier.
A mass spectral library search algorithm that identifies compounds that differ from library compo... more A mass spectral library search algorithm that identifies compounds that differ from library compounds by a single "inert" structural component is described. This algorithm, the Hybrid Similarity Search, generates a similarity score based on matching both fragment ions and neutral losses. It employs the parameter DeltaMass, defined as the mass difference between query and library compounds, to shift neutral loss peaks in the library spectrum to match corresponding neutral loss peaks in the query spectrum. When the spectra being compared differ by a single structural feature, these matching neutral loss peaks should contain that structural feature. This method extends the scope of the library to include spectra of "nearest-neighbor" compounds that differ from library compounds by a single chemical moiety. Additionally, determination of the structural origin of the shifted peaks can aid in the determination of the chemical structure and fragmentation mechanism of th...
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