PMID- 19108843 OWN - NLM STAT- MEDLINE DCOM- 20090715 LR - 20131121 IS - 1873-3778 (Electronic) IS - 0021-9673 (Linking) VI - 1216 IP - 19 DP - 2009 May 8 TI - Purification of high-throughput organic synthesis libraries by counter-current chromatography. PG - 4154-60 LID - 10.1016/j.chroma.2008.11.092 [doi] AB - Experiments were performed to evaluate whether counter-current chromatography (CCC) could function as an alternative purification method to reversed-phase high-performance liquid chromatography (RP-HPLC) and normal-phase supercritical fluid chromatography (SFC). RP-HPLC and SFC are the routine methods currently used in our high-throughput purification (HTP) facility for the purification of high-throughput organic synthesis (HTOS) libraries and medicinal chemistry reaction mixtures. Pre-equilibration of the solvent mixture layers was not mandatory for effective chromatography when hexanes-ethyl acetate-methanol-water (HEMW) solvent mixtures were used. Key to the use of CCC for high-throughput applications is the ability to effectively select a solvent system appropriate to each library member. Pilot-scale CCC elution time was used to estimate a starting solvent ratio and RP-HPLC retention time was then used to adjust solvent ratios within a particular library. It was also found that dimethyl sulfoxide (DMSO) and DMSO-methanol were suitable as sample injection solvents when using the HEMW solvent systems. FAU - Wagenaar, Frank L AU - Wagenaar FL AD - Abbott Laboratories, Abbott Park, IL 60064, USA. frank.wagenaar@abbott.com FAU - Hochlowski, Jill E AU - Hochlowski JE FAU - Pan, Jeffrey Y AU - Pan JY FAU - Tu, Noah P AU - Tu NP FAU - Searle, Philip A AU - Searle PA LA - eng PT - Journal Article DEP - 20081206 PL - Netherlands TA - J Chromatogr A JT - Journal of chromatography. A JID - 9318488 RN - 0 (Organic Chemicals) RN - 0 (Small Molecule Libraries) RN - 0 (Solvents) RN - 90Y4QC304K (Ketoprofen) RN - WK2XYI10QM (Ibuprofen) RN - Y4S76JWI15 (Methanol) RN - YOW8V9698H (Dimethyl Sulfoxide) SB - IM MH - Acylation MH - Chromatography, High Pressure Liquid MH - Countercurrent Distribution/*methods MH - Dimethyl Sulfoxide/chemistry MH - Equipment Design MH - Ibuprofen/isolation & purification MH - Ketoprofen/isolation & purification MH - Methanol/chemistry MH - Organic Chemicals/*chemistry MH - *Small Molecule Libraries MH - Solubility MH - Solvents/chemistry EDAT- 2008/12/26 09:00 MHDA- 2009/07/16 09:00 CRDT- 2008/12/26 09:00 PHST- 2008/09/30 00:00 [received] PHST- 2008/11/20 00:00 [revised] PHST- 2008/11/25 00:00 [accepted] PHST- 2008/12/26 09:00 [entrez] PHST- 2008/12/26 09:00 [pubmed] PHST- 2009/07/16 09:00 [medline] AID - S0021-9673(08)02113-4 [pii] AID - 10.1016/j.chroma.2008.11.092 [doi] PST - ppublish SO - J Chromatogr A. 2009 May 8;1216(19):4154-60. doi: 10.1016/j.chroma.2008.11.092. Epub 2008 Dec 6.