The proprietary Agilent data format was initially converted to the open-source mzML format using the MSConvert tool of the ProteoWizard software suite. The mzML format is a standardised open data format designed to store raw unprocessed data generated by MS instruments to be read by opensource MS software for further processing. The first step of the HRMS workflow involved extracting mass spectra from the total ion count chromatogram. To achieve this, the open-source mzMine package was used to automate the extraction of m/z values into a computer-processable format. The package mzMine is designed for performing analysis on large datasets of raw mass spectra data. The process involves detecting the masses above a certain threshold, extracting the ion chromatograms for each mass ion peak, and using an in-built pipeline method to calculate the intensity of each m/z peak over time which is written to a text file. The extracted mass ion peaks were then compared with those expected for each of the four topologies for a given pair of building blocks, with the number of water molecules lost for each imine condensation subtracted and possible mass ions with common ESI adducts incorporated, using pyOpenMS within the Python workflow. Of the 366 precursor combinations, 5 false positives (where POC species were incorrectly identified) and 14 false negatives (where POC species were not identified but had formed) were observed using the automated HRMS analysis, giving an overall 95% accuracy. From the 19 reaction combinations where researcher manual analysis and automated analysis did not agree (Figure and Table ), 12 (63%) were due to the misidentification of mixtures of topologies -the automated analysis correctly identified one topology, but on manual inspection a mixture of two species was observed. These false positives and negatives were likely observed due to the presence of other relatively low intensity mass ions that had similar m/z values to the cage topology peaks. Despite this, an overall 95% accuracy remained sufficient for this methodology to be carried forward with confidence in the automated analysis workflow, especially given the time savings that this approach affords for further HT screens.