Kinetic performance comparison of fully and superficially porous particles with a particle size of 5 mm: Intrinsic evaluation and application to the impurity analysis of griseofulvin Getu Kahsay a , Ken Broeckhoven b , Erwin Adams a , Gert Desmet b , Deirdre Cabooter a,n a KU Leuven, Department of Pharmaceutical Sciences, Pharmaceutical Analysis, Herestraat 49, O&N 2, PB 923, 3000 Leuven, Belgium b Vrije Universiteit Brussel, Department of Chemical Engineering, Pleinlaan 2, 1050 Brussels, Belgium article info Article history: Received 30 October 2013 Received in revised form 15 January 2014 Accepted 20 January 2014 Available online 31 January 2014 Keywords: Kinetic plots Superficially porous particles Loadability Griseofulvin 5 mm particles abstract After the great commercial success of sub-3 mm superficially porous particles, vendors are now also starting to commercialize 5 mm superficially porous particles, as an alternative to their fully porous counterparts which are routinely used in pharmaceutical analysis. In this study, the performance of 5 mm superficially porous particles was compared to that of fully porous 5 mm particles in terms of efficiency, separation performance and loadability on a conventional HPLC instrument. Van Deemter and kinetic plots were first used to evaluate the efficiency and performance of both particle types using alkylphenones as a test mixture. The van Deemter and kinetic plots showed that the superficially porous particles provide a superior kinetic performance compared to the fully porous particles over the entire relevant range of separation conditions, when both support types were evaluated at the same operating pressure. The same observations were made both for isocratic and gradient analysis. The superior performance was further demonstrated for the separation of a pharmaceutical compound (griseofulvin) and its impurities, where a gain in analysis time of around 2 could be obtained using the superficially porous particles. Finally, both particle types were evaluated in terms of loadability by plotting the resolution of the active pharmaceutical ingredient and its closest impurity as a function of the signal-to-noise ratio obtained for the smallest impurity. It was demonstrated that the superficially porous particles show better separation performance for griseofulvin and its impurities without significantly compromising sensitivity due to loadability issues in comparison with their fully porous counterparts. Moreover these columns can be used on conventional equipment without modifications to obtain a significant improvement in analysis time. & 2014 Elsevier B.V. All rights reserved. 1. Introduction Despite the impressive improvements made in separation efficiency and analysis time by the introduction of small particle columns operated at ultra-high pressures, pharmaceutical ana- lyses are still largely performed on conventional, 250  4.6 mm fully porous 5 mm particle columns [1]. This certainly has to do with the fact that numerous official methods (cfr. Pharmacopoeia analyses) are described on these large particle columns and that many pharmaceutical laboratories simply are not yet equipped with the most recent, low-dispersion ultra-high performance liquid chromatographs (UHPLC). As a compromise to obtain ultra-high efficiencies at conven- tional backpressures, superficially porous particles (also called core–shell particles) were (re-)introduced on the market in 2006. These particles, with a typical nominal diameter of 2.6–2.7 mm, consist of a solid core surrounded by a porous shell. It has been demonstrated on multiple occasions that superficially porous par- ticles exhibit extra-ordinarily high efficiencies, with minimum reduced plate heights ranging between 1.3 and 1.5 [2–4]. The relatively large size of the core–shell particles (in compar- ison with sub-2 mm fully porous particles), moreover results in permeability values and hence column backpressures that are compatible with conventional HPLC instrumentation. In fact, it has been demonstrated that – due to the combination of high column efficiency and permeability – superficially porous particles are able to reach plate counts in the practical range of separation efficien- cies equally fast as fully porous sub-2 mm particles, when the latter are operated at 1000 bar and the former only at 600 bar [5,6]. It has, however, been suggested that conventional LC systems are not suitable to record the peaks eluting from these high- efficiency core–shell columns. A conventional HPLC can easily contribute up to 50% of the peak variance for e.g. a core–shell column with dimensions of 50  4.6 mm, eluting a compound with Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/talanta Talanta 0039-9140/$ - see front matter & 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.talanta.2014.01.050 n Corresponding author. Tel.: þ32 16323442; fax: þ32 16323448. E-mail address: deirdre.cabooter@pharm.kuleuven.be (D. Cabooter). Talanta 122 (2014) 122–129