Details of Grant 

EPSRC Reference:	EP/J016578/1
Title:	Investigation of the separation mechanism in hydrophilic interaction chromatography.
Principal Investigator:	McCalley, Professor D
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Faculty of Health and Applied Sciences
Organisation:	University of the West of England
Scheme:	Standard Research
Starts:	29 October 2012	Ends:	28 October 2014	Value (£):	151,902
EPSRC Research Topic Classifications:	Analytical Science
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:
Panel History:	Panel Date Panel Name Outcome 08 Feb 2012 EPSRC Physical Sciences Chemistry - February 2012 Announced
Summary on Grant Application Form
Chromatography is a method of separating and analysing important chemicals such as ethical pharmaceuticals, drugs of abuse, food additives, pesticides and compounds in biological fluids that may be indicative of disease. A popular variant is high performance liquid chromatography, where the sample is introduced into a liquid stream (the "mobile phase") and passed through a column containing particles of the separation medium (the "stationary phase"). If these particles are made smaller, then the separations improve and they can be accomplished in minutes or even seconds, rather than hours or days. Small particles however, require high pressures to force the liquid through, hence the term high performance (or high pressure) liquid chromatography (HPLC). A detector situated at the end of the column senses the separated chemicals and allows them to be quantified. The annual world market for instruments and consumables in HPLC is several billion dollars; tens of thousands of analyses are carried out daily in the UK alone. Thus, faster and more efficient variations of the technique are continually being sought. One of these is hydrophilic interaction chromatography (HILIC), a technique that has significant advantages over the commonly used separation procedure (reversed-phase, RP), particularly for the fast analysis of drugs and compounds of clinical significance. Many of these compounds have only weak interactions with the usual RP columns and thus give poor separations. However, the mechanism of HILIC is poorly understood, which makes it difficult to design the separation conditions. Some separations seem to work very well, whereas others do not, for no apparent reason. The aim of this research is to elucidate the principles of the HILIC separation mechanism and to elucidate the experimental parameters that are most influential on the separation. This knowledge will be used to develop a "tool box" approach to apply the technique to separations that have proved difficult by conventional techniques. The idea is to apply an automated series of HILIC separations using different experimental conditions that generate different selectivity, such that an optimum for the analysis can be chosen. The study is of particular importance to the pharmaceutical industry especially in connection with new methods of drug design, such as "fragment based drug discovery" which involve synthesis of more complex structures using small building blocks each containing some desirable property of the final compound. Many of these building blocks are small polar molecules that should be very well suited to the HILIC technique. All pharmaceuticals need to be carefully screened for the presence of impurities, that may give rise to undesirable physiological side effects. HILIC can be used for example to assess the presence of residues of these polar starting materials in the final product. HILIC appears less susceptible to "overload", a phenomenon where distortion of the separation takes place when larger amounts of material are analysed. Overload can cause interference between large peaks of the active pharmaceutical ingredient and small quantities of impurities. The proposed work will require the development of a mixture of compounds of different structure that can be used to probe the various contributions to retention in HILIC. While the HILIC technique is very simple in practice, it appears that there are many complex factors which contribute to the separations. For example, many important pharmaceuticals, drugs of abuse, and compounds of biomedical significance are charged species, which adds an extra dimension of complexity to the separation mechanism. Understanding the importance of these various contributions will allow separations to be designed which can fully exploit the useful differences between HILIC and conventional separation methods.
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