High-speed screening of combinatorial libraries by gradient packed-column supercritical fluid chromatography

Packed-column supercritical fluid chromatography (pSFC) with a fast composition gradient is used as a rapid screening tool for combinatorial chemistry. The advantages of fast analysis speed and fast recovery to initial conditions are demonstrated. Retention time reproducibility is similar to isocratic analyses by pSFC and ranges from 0.37 to 0.64% relative standard deviation. A mixture of beta-blockers illustrates the 'normal phase' retention mechanism. For these solutes and a range of analytes, the peak width is relatively constant. Such behavior permits the classical peak capacity equation to be reduced to a simple, straightforward form. Using this as a performance metric, pSFC is shown to be 5-10 times faster than reversed phase HPLC for library screening.