Figure shows that the NEIMS algorithm, across all three accuracy metrics and both libraries comprising molecules outside of the algorithm's training set (MoNA f and IOCB), fails to consistently predict reliable EIMS spectra of amino acids by our measures. Specifically, amino acids within the NEIMS training set (NIST17) display the highest accuracy with mean RMSE, SCA, and WCS values of 9.64, 37.3°, and 0.84 respectively. The accuracy of predicted amino acid spectra within the IOCB library followed those within NIST17 with mean RMSE, SCA, and WCS values of 12.7, 82.1°, and 0.20 respectively. The lowest accuracy recorded was therefore the predicted amino acid spectra within MoNA f , with mean RMSE, SCA, and WCS values of 13.0, 64.7°, and 0.63 respectively. A deeper understanding of these results comes from measuring the impact on accuracy of differences in physicochemical properties and derivatization (Table .1). Figure shows no clear effect of molecular weight or hydrophobicity on prediction accuracy for any metric or library. Low correlations between hydrophobicity and all accuracy metrics, calculated as coefficients of determination (R 2 ), range from 0.01-0.13 across all libraries (Table .2). Similarly low correlations between molecular weight and accuracy typically range from 0.01-0.13 across each library and accuracy metric. The one exception of IOCB/RMSE (R 2 =0.38) seems likely to reflect the small sample size of the IOCB library in that it shows a counterintuitive negative correlation: larger, more complex molecules are easier to predict. Accuracy metrics are compared across MTBSTFA derivatized (Deriv) and underivatized (Free) amino acids for the NIST17 and IOCB libraries. (A) Amino acid spectra within the NIST17 library, when accuracy is measured via RMSE, display a significant difference in accuracy (p-value < 0.001) between MTBSTFA derivatized (Deriv) and underivatized (Free) amino acid spectra. All other comparisons (B-F) are found to be not significantly different (p-value > 0.05). The MoNA database was omitted from this analysis as there were no unique MTBSTFA monosubstituted α-amino acid spectra within MoNA.