HPLC, UHPLC
An Extension to Core-Shell Particle Technology – New Applicability at High pH.
Mar 03 2015
Author: Mark Woodruff on behalf of Fortis Technologies Ltd
This article discusses the use of core-shell particles in terms of the current market trends, where they are and what is next in the evolution of the technology. There is no doubt that core-shell particles provide very high efficiency separations at reduced backpressures, however quite how these particles work is still the subject of much on-going work and discussion. What also isn’t in doubt is that manufacturers will continue to expand the offerings available. One important such development will be the extension of core-shells ability to operate at extremes of pH.
This can be achieved successfully through a surface grafting technology, Fortis SpeedCore pH Plus, to give a material, which possess an increased lifetime at high pH for basic drug analysis.
Introduction
Core-shell particles for use in HPLC have become the current trend in the last few years, commercially introduced in their current small particle form by Advanced Materials Technology in 2006, they provide the capability for high speed, highly sensitive, rapid separations. DuPont first described the technology for use in separations of peptides and proteins back in the 1970’s, but this was utilising relatively large particles sizes and featured lower control over the outer shell thickness than current technology.
Now since various small particles, 1.7μm, 2.6μm, 5μm are commercially available from several manufacturers [1], the technology has seen an increase in uptake, being one of the most discussed subjects at conferences, the introduction of new core-shell particles and phases outstripping traditional porous particles by 10:1 according to Majors [2].
Due to the mass transfer, reduced band broadening and particle morphology of these core-shells, analysts are utilising these particles effectively to operate at high speed, whilst achieving high resolution, high efficiency separations. However there is still a steep learning curve for practitioners seeking to know more about the attributes of these particles and the way that the mechanisms operate [3]. Initially thoughts were based around the particle size distribution being tighter and the reduced mass transfer. However now it would appear that the A and B terms in the Van-Deemter equation are playing a bigger role than first thought since these core-shell particles can be packed more effectively with smaller ‘dwell-volume’ [4].
Limitations
Core-shell particles have a very attractive attribute in efficiency gains, however can they totally replace traditional fully porous particles? Well there are several limitations [5], scaling from small 2.6μm to larger 5μm and 10μm particles to provide preparative capabilities, selectivity choices, lifetime, and pH range to name a few. If all of these can be overcome then potentially yes, it remains to be seen if it is achievable, but there is certainly a lot of hard work to be done to get to that point.
There are a few products now available (Figure 1) where you can scale from one particle size to another, although it will need to be shown that the separation is not altered by any subtle changes in physical characteristics, shell thickness, shell uniformity, pore structure or carbon loading.
Stationary phase selectivity is certainly a variable that many manufacturers are focussed on; as most have vast experience having produced many phase chemistries on traditional fully porous particles. There is no reason why any of these chemistries (Figure 2) cannot be applied to core-shell particles. Therefore expect a continuous flow of product additions in this space. If you do not increase selectivity options many difficult applications, positional isomers, metabolites and homologous series, will continue to prove a challenge with the use of high efficiency alone.
Another limitation with core-shell particles is the useable pH range; a look through the current literature suggests that pH 2-8 is the most recommended range with some manufacturers claiming 2-9 or possibly 2-10. Since this is generally marketing literature with fine print such as ‘the gradient pH range is different to the isocratic range’, or ‘only certain organic buffers may be used’, then it is clearly debatable how robust these phases currently are.
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