Drug discovery chromatography

Direct property prediction is a standard technique in drug discovery. "Reverse property prediction can be exemplified with chromatography application databases that contain separations, including method details and assigned chemical structures for each chromatogram. Retrieving compounds present in the database that are similar to the query allows the retrieval of suitable separation conditions for use with the query (method selection). 

Drug discovery applications also provide insights for the eventual determination of the compounds in a forensic or toxicological setting this is another area in which multidimensional chromatography allows the direct injection of bodily fluids. For... 

The drug discovery route to rizatriptan (1) began with the preparation of 1-(4 -nitrobenzyl)-l,2,4-triazole 5 using 4-nitrobenzyl bromide (4) and 1,2,4-triazole. (Scheme 4.1). Benzylation of the sodium salt of 1,2,4-triazole prepared with NaH was not regioselective and afforded a 1.5 1 mixture of l-(4 -nitrobenzyl)-1,2,4-triazole (5) and its regioisomer, 4-(4 -nitrobenzyl)-l,2,4-triazole. The desired isomer 5 was isolated in 52% yield after silica gel chromatography. Hydrogenation... 

Beaudry F. et al., 1998. In vivo pharmacokinetic screening in cassette dosing experiments Use of online Pros-pekt liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry technology in drug discovery. Rapid Commun Mass Spectrom 12 1216. 

Hsieh Y. et al., 2000. Direct analysis of plasma samples for drug discovery compounds using mixed-function column liquid chromatography tandem mass spectrometry. Rapid Commun Mass Spectrom 14 1384. 

Thin-layer chromatography (TLC) is one of the most popular and widely used separation techniques because it is easy to use and offers adequate sensitivity and speed of separations. Furthermore, multiple samples can be run simultaneously. It can be used for separation, isolation, identification, and quantification of components in a sample. The equipment used for performance of TLC, including applications of TLC in drug discovery process, is covered in Chapter 13. This technique has been successfully used in biochemical, environmental, food, pharmacological, and toxicological analyses. 

Zhao, Y., Woo, G, Thomas, S., Semin, D., Sandra, P. Rapid method development for chiral separation in drug discovery using sample pooling and supercritical fluid chromatography-mass spectrometry. J. Chromatogr. A 2003, 1003, 157-166. 

Maftouh, M., Granier-Loyaux, C., Chavana, E., Marini, J., Pradines, A., Vander Heyden, Y., Picard, C. Screening approach for chiral separation of pharmaceuticals Part in. Supercritical fluid chromatography for analysis and purification in drug discovery. J. Chromatogr. A 2005, 1088, 67-81. 

Mei H, Hseih Y, Nardo C, Xu X, Wang S, et al. 2003. Investigation of matrix effects in bioanalytical high performance liquid chromatography/tandem, mass spectrometrometic assay application to drug discovery. Rapid Commun Mass Spectrom 17 97-103. 

---