In HPLC the emphasis is on limiting the diffusion distance, assuming the diffusion coefficients are fixed. The shorter the diffusion distance, the higher the optimum linear velocity. Totally porous sub-2 μm particles limit the diffusion distance by making the particles smaller. Porous shell particles limit the diffusion distance by decreasing the total diffusion distance to the thickness of the porous shell.

In HPLC the emphasis is on limiting the diffusion distance, assuming the diffusion coefficients are fixed. The shorter the diffusion distance, the higher the optimum linear velocity. Totally porous sub-2 μm particles limit the diffusion distance by making the particles smaller. Porous shell particles limit the diffusion distance by decreasing the total diffusion distance to the thickness of the porous shell.

The Aurora SFC Fusion™ A5 system lowers detector noise for a 10-fold increase in sensitivity. UV detector noise has generally been an order of magnitude worse with SFC than with HPLC using the same detector. Detector noise is the result of several components in the SFC system. This paper will examine three components that can be managed using the Aurora SFC Fusion A5 system to minimize noise in the detector and open the door to a wide range of applications.

Very high sample throughput is often required in applications with larger numbers of samples, such as library screening. It is often true that chromatograms can be generated in less than a minute, but the system cycle time is extended by 1-2 additional minutes to prepare to inject, perform detector balance, store the method with the previous runs raw data, external needle wash, needle and loop wash steps, etc.      

There is a surprising scarcity of chromatograms collected using small particles in SFC. What few samples exist concentrate on the application, such as high-speed screening, and do not emphasize the quality of the separations.

Here, Zorbax RX-Sil (bare silica) 1.8 um particles in a 4.6 x 50 mm column (Agilent Technologies) are used to demonstrate high speed, intermediate efficiency with symmetrical peaks, using a test mix of small drug-like molecules. The last 3 peaks exhibit over 9000 plates each, and 650-1000 plates/sec.

This brief paper highlights 4 chiral separations to illustrate the speed, resolution and sensitivity of the new generation of analytical SFC instruments. The Aurora SFC Fusion A5TM used in this paper extends the separation range of an Agilent HPLC (1100/1200) making it an ideal instrument for Chiral analysis. Additionally, we show how the use of a temperature controlled column compartment offers a wider range of operating conditions and can contribute to reduced detector noise.

It is well established that SFC is a valuable technique for Chiral analysis in the early stages of drug research and development. Recent technology offerings have extended this utility to enantiomeric excess (EE) calculations.
This is made possible by enhancements in dynamic range and reduction of spurious noise delivered by the SFC Fusion A5 module from Aurora SFC. This study demonstrates that technical advances in the Fusion A5 permit quantitation, even when the lesser component is less than .1% of the main component. The ICH guidelines require quantitation of any impurity representing >0.1% of the total area. In this study we are using SFC-UV DAD to look for trace components representing <0.05% of the total area.

It is often desirable to transfer a method from a long column, packed with larger particles, to a shorter column with smaller particles, to reduce analysis time. In order for method transfer to be feasible, the stationary phase must remain consistent independent of particle size or pressure drops.

The chromatograms shown demonstrate consistent selectivity, even though the particle diameter was decreased from 5μm to 3.5μm and then to 1.8μm.

The primary mechanism for delivering drugs is orally in the form of tablets or capsules. The ease and convenience of taking a tablet has helped to insure patient compliance with treatment.

An aged, stressed antibiotic tablet was crushed, dissolved in methanol, sonicated and fil-tered. Using pure methanol as the modifier, a single large peak representing sulfamethox-azole emerged, along with a number of small contaminant-breakdown peaks.