Compound classification, automated

Vogt, L., Groger, T. and Zimmermann, R. (2007) Automated compound classification for ambient aerosol sample separations using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry. Journal of Chromatography A, 1150, 2 12. 

Automated compound classification is a further approach for rapid library design. 

MS has recently been used to measure compounds with significant levels of impurities and solubilities below the quantitation limits of other methods. Guo et al.46 described the use of LC/MS for solubility measurements in buffer solutions in a 96-well plate. Fligge et al.47 discussed an automated high-throughput method for classification of compound solubility. They integrated a Tecan robotic system for sample preparation in 384-well plates and fast LC/MS for concentration measurement. This approach is limited by LC/MS throughput. 

HPLC provides reliable quantitative precision and accuracy, along with a linear dynamic range (LDR) sufficient to allow for the determination of the API and related substances in the same run using a variety of detectors, and can be performed on fully automated instrumentation. HPLC provides excellent reproducibility and is applicable to a wide array of compound types by judicious choice of HPLC column chemistry. Major modes of HPLC include reversed phase and normal phase for the analysis of small (<2000 Da) organic molecules, ion chromatography for the analysis of ions, size exclusion chromatography for the separation of polymers, and chiral HPLC for the determination of enantiomeric purity. Numerous chemically different columns are available within each broad classification, to further aid method development. 

Topological descriptors can be computed very quickly for a huge number of compounds. These descriptors are able to reproduce the intuitive classification of structural formulas. For this reason, topological descriptors are a good choice to describe the diversity of huge virtual libraries in an automated way. 

Classification methods based on substructural descriptors and such index techniques have also been applied in the field of chemical hazards such as toxic effects [167, 168], carcinogenicity [116, 144, 149, 150, 156, 167, 168] and mutagenicity [164, 165, 168, 232] not without success. Attempts are made to provide automated predictions of such hazards for chemical compounds of interest, which is certainly helpful in setting priorities for biological testing. It is important, however, to realize that such predicted data can never be taken for granted and must not be allowed to replace experimental measurements [169]. 

The results of the automated 2D NMR, MS, and HPLC analysis were combined to a final assignment. Classification true of the HPLC analysis was not taken into consideration. Contradictory results lead to the final category unclear. Seven samples remained unclassified and in these cases the classification was done by the manual interpretation of the H NMR spectra. This analysis showed that 78 compounds were obtained by the synthetic procedure. 

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