Mass-directed fractionation and isolation of pharmaceutical compounds by packed-column supercritical fluid chromatography/mass spectrometry

An automated packed-column semi-preparative supercritical fluid chromatogra phy/mass spectrometry (SFC/MS) system incorporating mass-directed fraction collection has been designed and implemented as an alternative to preparati ve HPLC and preparative HPLC/MS (PrepLC/MS) for the purification of pharmac eutical compounds. The system incorporates a single quadrupole mass spectro meter and a supercritical fluid chromatograph. Separations were achieved us ing a binary solvent system consisting of carbon dioxide and methanol. Puri fication of SFC-separated compounds was achieved incorporating mass-directe d fraction collection, enabling selective isolation of the target molecular weight compound and eliminating the collection of undesired compounds (e.g ., by-products, excess starting materials, etc.). Cross contamination betwe en fractions and recoveries of the system were investigated. Mass spectrome ter ionization with basic mobile additives is discussed, and examples of pr eparative SFC/MS chiral separations are presented. Early experiences sugges t SFC will be a powerful and complementary technique to HPLC for the purifi cation of pharmaceutical compounds. Copyright (C) 2001 John Wiley & Sons, L td.