The Autumn 1998 meeting of the UK NMR Discussion Group was held on 22 September 1998 in the magnificent surroundings of the Sir James Black Conference Centre at Zeneca Pharmaceuticals, Alderley Park, Cheshire, UK. The meeting was designed as a workshop/symposium under the auspices of the EU Biomed 2 Concerted Action “Development of Hyphenated Analytical Chemical Techniques (BMH4-CT97-2533)”. The subject matter was the development and application of hyphenated NMR methodologies in pharmaceutical chemistry and biochemistry. The meeting, which brought together many of the main figures in the field, had an excellent attendance and attracted over 90 participants from industry and academia.
The chairman of the NMR Discussion Group, Professor Jeremy Nicholson, (Imperial College, London, UK) introduced the morning speakers. The meeting began with an overview by Professor John Lindon (Imperial College, London, UK) of the history of direct coupling of HPLC with NMR spectroscopy with reference to other separations techniques which have also been hyphenated such as supercritical fluid chromatography, capillary electrophoresis and capillary electrochromatography. The solutions to problems of sensitivity and dynamic range that made HPLC-NMR a successful approach were outlined and prospects for the future with particularly the importance of HPLC-NMR-MS were summarised. This was followed by Dr Steven Bobzin (Searle-Monsanto, St. Louis USA) who described how he was using directly-coupled HPLC-NMR to derive structures of marine natural products which might be leads to develop new areas of medicinal chemistry. A major aspect of the work was to devise an efficient scheme to allow rapid recognition of previously characterised compounds. Next came Professor Ian Wilson (Zeneca Pharmaceuticals, Alderley Park, UK) who described some recent studies on directly-coupled HPLC-NMR-MS of the structure of both animal and plant metabolites. He also summarised his recent studies on using superheated water as an eluent in directly-coupled HPLC-NMR and finally tried to claim the prize for the greatest degree of hyphenation of the day with a description of HPLC-UV-NMR-MS-IR. The morning session ended with Mrs Nisha Mistry (GlaxoWellcome, Stevenage, UK) who described an elegant study of the identification of the 10 isomers present in the neuromuscular blocking drug atracurium using chiral HPLC-NMR and chiral HPLC-CD.
After an excellent lunch provided by Zeneca Pharmaceuticals the afternoon session continued under the chairmanship of John Lindon. He introduced the first speaker, Dr Alastair Swanson (Pfizer Pharmaceuticals, Sandwich, Kent, UK) who gave an exposition of the problems associated with HPLC-NMR-MS and the solutions which his group have evolved. This talk provided much practical and useful expertise that should be of widespread use to other practitioners of HPLC-NMR. The next speaker was John Shockcor (Dupont Pharmaceuticals, Newark, Delaware, USA) who showed applications of HPLC-NMR-MS in drug metabolism both for determining the metabolic profile of development drugs but also for investigating drug metabolite reactivity, in particular the reaction of drug metabolites with glutathione. The afternoon continued with Dr Klaus Pusecker (Novartis Pharma, Basel, Switzerland) who described his studies carried out at the University of Tubingen, Germany on developing miniaturisation of separations coupled to NMR spectroscopy. He showed the system developed for CE-NMR, CEC-NMR and capillary HPLC-NMR, illustrating the methods with results from the separation of natural products and drug metabolites. The final speaker of the formal session was Dr Manfred Spraul (Bruker Analytik, Rheinstetten, Germany) who outlined recent developments in technology relevant to HPLC-NMR and HPLC-NMR-MS. He gave some thoughts on future developments to improve overall sensitivity such as those based on NMR detectors cooled to liquid helium temperature to decrease the noise figure.
After a short tea break the meeting continued with a general discussion on hyphenated techniques chaired by Professor Steen Honoré Hansen (Royal Danish School of Pharmacy, Copenhagen, Denmark), the co-ordinator of the EU Concerted Action. This allowed the meeting participants a good opportunity to raise scientific and practical points and to obtain answers to questions from some of the leading proponents of the methods. Overall it was judged that the meeting was very successful in terms of scientific interchange and in the opportunity it gave for social interaction.
John Lindon
Imperial College of Science, Technology and Medicine, London