title: Mass-directed fractionation and isolation of pharmaceutical compounds by packed-column supercritical fluid chromatography/mass spectrometry.
abstract: An automated packed-column semi-preparative supercritical fluid chromatography/mass spectrometry (SFC/MS) system incorporating mass-directed fraction collection has been designed and implemented as an alternative to preparative HPLC and preparative HPLC/MS (PrepLC/MS) for the purification of pharmaceutical compounds. The system incorporates a single quadrupole mass spectrometer and a supercritical fluid chromatograph. Separations were achieved using a binary solvent system consisting of carbon dioxide and methanol. Purification of SFC-separated compounds was achieved incorporating mass-directed 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 between fractions and recoveries of the system were investigated. Mass spectrometer ionization with basic mobile additives is discussed, and examples of preparative SFC/MS chiral separations are presented. Early experiences suggest SFC will be a powerful and complementary technique to HPLC for the purification of pharmaceutical compounds.
authors.affiliation: Dupont Pharmaceutical Research Laboratories, Executive Drive, San Diego, CA 92121, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Barber
authors.forename: I
authors.initials: I
authors.lastname: Hardt
authors.forename: D B
authors.initials: DB
authors.lastname: Kassel
mesh_terms: D002245:Carbon Dioxide; D002853:Chromatography, Liquid / Q000295:instrumentation* / Q000379:methods; D013058:Mass Spectrometry / Q000295:instrumentation* / Q000379:methods; D000432:Methanol; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000302:isolation & purification
chemical_list: D004364:Pharmaceutical Preparations; D002245:Carbon Dioxide; D000432:Methanol