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1	Quantification of Pharmaceuticals at the sub-cellular level using the NanoSIMS Dost, Maryam January 2024 (has links) Mass spectroscopy imaging (MSI) has become a vital tool in modern research due to its ability to visualize the spatial distribution of molecules within tissue samples. The collaboration between researchers at AZ, the University of Gothenburg, and Chalmers University of Technology using the NanoSIMS instrument and MSI-SIMS technology has opened up new avenues of exploration in pharmaceutical development, particularly in examining drugs and metabolites at sub-cellular levels. This groundbreaking research has the potential to significantly improve the efficacy and safety of future pharmaceutical products. NanoSIMS possesses a unique imaging and processing technique that enables high-resolution imaging of cellular structures and subcellular compartments. This powerful tool allows for the visualization and measurement of elements and isotopes at the subcellular level. The technique involves bombarding a sample with a focused primary ion beam, which causes the emission of secondary ions. These secondary ions are then analyzed to determine the elemental and isotopic composition of the sample. NanoSIMS is particularly useful for analyzing biomolecules since traditional Mass spectrometry methods cannot provide information about how molecules behave at the cellular level. Given that many of the drugs used today have intra-cellular targets, hence understanding the drug's cellular pathways is extremely important, especially in cases where the risk for organ toxicity is high due to the high dosage of the drugs. Our data from the image analysis indicated the presence of amiodarone inside the lysosomes; however, the lack of enrichment from the 13C portion of the dual-labeled molecule made it difficult to reach a variation below the LOD. Since our LOD is relatively high when working with 13C12C, we focused on the fact that accuracy, precision, and sensitivity would be the most crucial factors in our study. After adjusting these parameters, we obtained an image that made the measurement possible. This project aims to utilize a dual-labeled drug (13C and 127I) to bridge the absolute quantification ability of the 13C labeling scheme to the more sensitive labeling scheme. The focus of this study lies therefore on optimization and the relationship between Spatial resolution, Sensitivity, Mass Resolution, Accuracy, and Precision. This technique is extremely promising, but the limit of detection is relatively high mainly due to the high percentage of carbon in the sample. Despite this fact, we were able to present some valuable data. Our analysis showed that the sensitivity of the 127I is much better than 13C, however, we produced an image where the ratio between the labels was above the detection limit. Using this data, a Relative sensitivity factor (RSF) value was measured, and the concentration of the drug could be estimated by applying the quantification equation. Mass spectroscopy imaging AstraZeneca Nanosims Therapeutics pharmacokinetics pharmacodynamics Quantitative Visualization calibration curve RSF pharmacology Data Analysis Chemistry Quantification isotopes Pharmaceuticals subcellular drug drug target nucleotide biodistribution Bioanalytical electrochemistry spectroscopy mass spectrometry analytical separations Analytical Chemistry ROI Bioanalytical Chemistry Masspektroskopi avbildning AstraZeneca Nanosims Terapeutik farmakokinetik farmakodynamik Kvantitativ visualisering kalibreringskurva RSF farmakologi Dataanalys Kemi Kvantifiering isotoper Läkemedel subcellulär läkemedel läkemedelsmål bioskopisk elektrofördelning nukleotid bioskopisk bioskopisk distribution masspektrometri analytiska separationer analytisk kemi bioanalytisk kemi Analytical Chemistry Analytisk kemi

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Quantification of Pharmaceuticals at the sub-cellular level using the NanoSIMS