New surface-modified nanoparticles as matrices to enhance mass spectrometric analysis of substance of abuse by matrix assisted laser desorption ionization

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Mass spectrometry (MS) has evolved to become a key analytical tool for identifying and quantifying molecules in a range of environmental, biological, and health disciplines. The questions of "what is in the sample?" and "how much?" remain critical components of biological studies. In fact, liquid chromatography (LC)-MS, equipped with electrospray ionization (ESI), is considered by many as the gold standard approach and it is used widely in clinical, environmental and forensic laboratories. However, LC-MS is time consuming, often requires substantial sample preparation, and uses a large amount of organic solvents. Matrix assisted laser desorption ionization (MALDI)-MS is an alternative analytical strategy as it is fast (100 times faster than LC-MS), simple, uses fraction amounts of solvents, and tolerates impurities in a sample (i.e. less sample preparation time). MALDI-MS is ideal for large molecules, such as proteins, but the analysis of small molecules, such as psychoactive substances, is hampered by the use of a "matrix". The matrix is required to facilitate the ionization of target compounds, a precondition for MS analysis. It interferes, however, in the analysis at the lower mass range, where small molecules will appear. The matrix forms cluster ions and creates significant background noise. The bottleneck in expanding the use of MALDI-MS for small molecules is the design of new matrices that allows for the analysis at the low mass range. In this proposal, novel MALDI matrices will be designed. The matrices are surface modified nanoparticles (nanodiamonds and gold nanoparticles), to which either conventional matrices or amino acids are grafted on the surface. The main idea is to take advantage of the optical properties of the gold nanoparticles and nanodiamonds and to combine this with the ionization ability of conventional matrices for the analysis of small organic compounds. Our initial investigation showed the promise of such a strategy to analyze small pharmaceuticals. Therefore, new matrices will be designed then tested on psychoactive substances of concern to Canadians, namely cannabis metabolites, opioids (e.g. fentanyl), and amphetamines. Both the legalization of cannabis and the ongoing opioid crisis have created urgency for the development of fast and simple analytical strategies. Our driving hypothesis is that functionalizing gold and nanodiamond nanoparticles with conventional matrices and amino acid moieties will facilitate MALDI-MS analysis of psychoactive substances within biological samples (urine and plasma). In the long term, the aim of the research program is to develop simple MALDI-MS based assays using nanoparticles to identify and quantify psychoactive substances. I envision developing simple assays that are automated and provide fast results regarding the illegal or harmful use of psychoactive substances. The technology can also be applied to other small molecules of concern to health, safety and the environment.