Mass-directed fractionation and isolation of pharmaceutical compounds by packed-column supercritical fluid chromatography/mass spectrometry.
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.
Wang
T
T
Dupont Pharmaceutical Research Laboratories, Executive Drive, San Diego, CA 92121, USA.
Barber
M
M
Hardt
I
I
Kassel
D B
DB
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
D004364:Pharmaceutical Preparations; D002245:Carbon Dioxide; D000432:Methanol