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Department of Chemistry
Queen Mary, University of London Mile End Road, London E1 4NS, UK Tel. +44 (0) 20 7882 6355 Fax. +44 (0) 20 8983 0470 E-mail : R.Whelpton@qmul.ac.uk |
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Department of Chemistry
Queen Mary, University of London Mile End Road, London E1 4NS, UK Tel. +44 (0) 20 7882 6355 Fax. +44 (0) 20 8983 0470 E-mail : R.Whelpton@qmul.ac.uk |
Robin Whelpton, PhD CChem MRSC: is a senior lecturer in Pharmaceutical Chemistry/Pharmacology at Queen Mary, University of London.
My research interests centre on the development and application of analytical methods for the determination of bioactive agents, drugs and other xenobiotic compounds and pharmacokinetics. The techniques employed include gas-chromatography with electron capture, nitrogen-phosphorus, flame ionization and mass spectrometric detection, high performance liquid chromatography with UV-VIS, fluorescence and coulometric detection, capillary electrophoresis and use of isotopically labelled drugs. Because the methods are applied to biomedical investigations the majority of work is collaborative, and includes investigations into the effects, metabolism and kinetics of endogenous peptides, the disposition and kinetics of a new photodynamic agent, temoporfin, the development and application of a rapid and highly sensitive method for the determination of plasma paracetamol (acetaminophen). Present studies are examining the role of excitatory amino acids in ischaemia and depression.
Peptides and catecholamines
This collaborative work with Dr. Adina Michael-Titus in the Neuroscience Section of the School of Medicine & Dentistry, includes refinement of HPLC-ED to determine very low concentrations of catecholamines and gradient HPLC to separate substance P and its metabolites and related tachykinin peptides. An innovative approach was to confirm the identity of the peptides by subjecting HPLC fractions to capillary electrophoresis. This work has been supported by a number of grants from the Wellcome Trust.
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Separation of substance P and 12 of its fragments by capillary electrophoresis. UV detection at 200 nm. |
Paracetamol
Paracetamol was used as a marker of gastric emptying in studies with Dr. David Goldhill, Academic Department of Anaesthetics, Royal London Hospital. This necessitated the development of a rapid but highly sensitive HPLC-ED method for the determination of paracetamol in blood or plasma. The synthesis of the propionyl homologue for use as an internal standard greatly improved the precision and accuracy of the technique. The work was funded in part by Janssen Pharmaceuticals.
Temoporfin
Temoporfin, the approved name for 5,10,15,20-tetra[m-hydroxyphenyl]chlorin (mTHPC) was first synthesized in the Department by Professor Bonnett and is currently being developed by Scotia Pharmaceuticals as a new photodynamic agent for the treatment of cancer under the trade name Foscan. Initial studies used reversed-phase HPLC with detection at 423 nm to investigate the disposition and kinetics of the drug in mammals. Later investigations used [14C]-labelled drug. These were collaborative studies with Dr. Adina Michael-Titus and Scotia Pharmaceuticals.
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Temoporfin |
Excitatory amino acids
Increasing interest in the role of glutamate in ischaemia and more recently depression led to collaborative studies with Dr Jon Stamford (Anaesthetics) and Dr Adina Michael-Titus. Glutamic and aspartic acids were quantified by isocratic HPLC with fluorescence detection, after derivatization with 2-mercaptoethanol/o-phthaldialdehyde.
Peptides and dopamine
Endogenous dopamine outflow from rat striatal slices in static and dynamic conditions, S. Khan, R. Whelpton and A.T. Michael-Titus, Neurosci. Res. Comm., 1995, 15, 145-153.
Substance P-(1-7) and substance P-(5-11) locally modulate dopamine release in rat striatum, S. Khan, N. Brooks, R. Whelpton and A.T. Michael-Titus, Eur. J. Pharmacol., 1995, 282, 229-233.
Evidence for modulatory effects of substance P fragments (1-4) and (8-11) on endogenous dopamine outflow in rat striatal slices, S. Khan, R. Whelpton and A.T. Michael-Titus. Neurosci. Lett., 1996, 205, 33-36.
N- and C-terminal substance P fragments modulate striatal dopamine outflow through a cholinergic link mediated by muscarinic receptors, S. Khan, E. Grogan, R.Whelpton and A.T. Michael-Titus, Neuroscience, 1996, 73, 919-927.
Substance P fragments and striatal endogenous dopamine outflow: Interaction with substance P, S. Khan, J. Sandhu, R. Whelpton and A.T. Michael-Titus, Neuropeptides, 1997, 32, 519-526.
Identification of substance P metabolites using a combination of reversed-phase high performance liquid chromatography and capillary electrophoresis, R. Whelpton, A.T. Michael-Titus, S.M. Stephens, K.W. Yau and D. Fengas, J. Chromatogr., 1998, 716, 95-106.
N- and C-terminal substance P fragments: different effects on striatal [3H]substance P binding and NK1 receptor internalisation, A.T. Michael-Titus, D. Blackburn, Y. Connolly, J.V. Priestley and R. Whelpton, Neuroreport, 1999, 10, 2209-2213.
Substance P modulation of striatal dopamine outflow is determined by M1 and M2 muscarinic receptors in male Wistar rats, S. Khan, R. Whelpton and A.T. Michael-Titus, Neuroscience Letters, 2000, 293, 179-182.
Gastric emptying (paracetamol)
Determination of paracetamol (acetaminophen) in blood and plasma using high performance liquid chromatography with dual electrode coulometric electrode quantification in the redox mode, R. Whelpton, K. Fernandes, K.A. Wilkinson and D.R. Goldhill, Biomed. Chromatogr., 1993, 7, 90-93
Gastric emptying in patients the day after cardiac surgery. D.R. Goldhill, R. Whelpton, J.A. Winyard, K.A. Wilkinson, Anaesthesia, 1995, 50, 122-125.
Double-blind, randomized study of the effect of cisapride on gastric emptying in critically ill patients. D.R. Goldhill, C.C. Toner, M.M. Tarling, K. Baxter, P.S. Withington and R. Whelpton, Critical Care Medicine, 1997, 25, 447-451.
A model of gastric emptying using paracetamol absorption in intensive care patients, M.M. Tarling, C.C. Toner, P.S. Withington, M.K. Baxter, R. Whelpton and D.R. Goldhill, Intensive Care Med., 1997, 23, 256-260.
Photodynamic therapy (temoporfin)
Distribution of temoporfin, a new photosensitizer for the photodynamic therapy of cancer, in a murine tumor model, R. Whelpton, A.T. Michael-Titus, S.S. Basra and M. Grahn, Photochem. Photobiol., 1995, 61, 397-401.
Binding of temoporfin to the lipoprotein fractions human serum, A.T. Michael-Titus, R. Whelpton, and Z. Yaqub, Br. J. Clin. Pharmacol., 1995, 40, 594-597.
Distribution and excretion of radiolabeled temoporfin in a murine tumor model, R. Whelpton, A.T. Michael-Titus, R.P. Jamdar, K. Abdillahi and M.F. Grahn, Photochem. Photobiol., 1996, 63, 885-891.
Excitatory amino acids
Imipramine and phenelzine decrease glutamate overflow in the prefrontal cortex - a possible mechanism of neuroprotection in major depression, A.T. Michael-Titus, S. Bains, J. Jeetle and R. Whelpton, Neuroscience, 2000, 100, 681-684.
Effects of sevoflurane on dopamine, glutamate and aspartate release in an in vitro model of cerebral ischaemia, C.C. Toner, K. Connelly, R. Whelpton, S. Bains, A. T. Michael-Titus, D.P. McLaughlin and J. A. Stamford, Br. J. Anaesthesia, 2001, 86, 550-4.
Last update : 12 May 2001
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Queen Mary, University of London
London E1 4NS
Tel. +44 (0) 20 7882 3252
Fax. +44 (0) 20 7882 7794
Email: chemistry@qmul.ac.uk
Maintained by: Dr. R.M. Nix