Prediction of UV and ESI-MS signal intensities.
All major pharmaceutical companies maintain large collections of compounds that are used either for screening against biological targets or as synthetic precursors. The quality assessment of these compounds is typically done by liquid chromatography combined with mass spectroscopy (LC/MS) and UV purity control. To facilitate the analysis of the analytical data, we have built computational models to predict UV and MS signal intensities under experimental LC/MS conditions. The discriminant partial-least-squares technique was used for classifying compounds into those most likely to yield a MS signal and others where the signal is below the detection limit (94% and 88% correct predictions, respectively). In the case of UV prediction, we compared this statistical linear-regression technique to a knowledge-based approach. A combination of both techniques proved to be the most reliable (96/98% correct predictions of UV-active/ UV-inactive compounds). Both models have been incorporated into the automated compound integrity profiling at F. Hoffmann-La Roche.
Mauser
Harald
H
F. Hoffmann-La Roche Ltd., Pharmaceuticals Division, CH-4070 Basel, Switzerland. harald.mauser@roche.com
Roche
Olivier
O
Stahl
Martin
M
Müller
Stephan
S
D002863:Chromogenic Compounds / Q000032:analysis / Q000737:chemistry; D003198:Computer Simulation; D005544:Forecasting; D015394:Molecular Structure; D012815:Signal Processing, Computer-Assisted; D021241:Spectrometry, Mass, Electrospray Ionization; D014466:Ultraviolet Rays
D002863:Chromogenic Compounds