David J. Wilkinson

Iridium-catalysed labelling of anilines, benzylamines and nitrogen heterocycles using deuterium gas and cycloocta-1,5-dienyliridium(I) 1,1,1,5,5,5-hexafluoropentane-2,4-dionate

A wide range of variously substituted anilines, benzylamines, and nitrogen heterocycles may be conveniently deuterated by exchange with deuterium gas and cycloocta-1,5-dienyliridium(I) 1,1,1,5,5,5-hexafluoropentane-2,4-dionate. The isotopic exchange can be carried out efficiently in dimethylformamide or dimethylacetamide, hence it is directly applicable to the deuteration of polar compounds such as pharmaceuticals. Isotope incorporation is rapid and yields ortho-regiospecificity.

Parallel chemistry investigations of ortho-directed hydrogen isotope exchange between substituted aromatics and isotopic water: novel catalysis by cyclooctadienyliridium(I)pentan-1,3-dionates

Abstract Novel iridium-based catalysts which promote ortho -directed hydrogen isotope exchange between substituted aromatics and isotopic water have been identified via a combination of screening and subsequent ligand optimisation. The catalysts are more active, operate at lower temperature and are applicable to a wider variety of substrates than previously known systems.

Preparation of remacemide hydrochloride labelled with carbon‐14, carbon‐13, deuterium and tritium

The anti-epileptic agent remacemide hydrochloride has been prepared labelled with 14C, from [carbonyl-14C]acetophenone, and with 13C from [13C6]benzene, [1,2-13C]acetyl chloride and [1-13C]glycine. [2-3H]Glycine was utilised to prepare remacemide labelled with tritium at low specific activity. In addition other 2H- and high specific activity 3H-isotopomers of the drug, and of an active metabolite of the drug, were prepared by hydrogen isotope exchange methodology. The R-12C/S-14C and S-12C/R-14C pseudoracemic drugs were also prepared by a synthesis involving resolution of a 14C-labelled amine intermediate via fractional crystallisation of the dibenzoyltartrate salts. Copyright

A RIA combined with spe for the determination of a dual D2-receptor and β2-adrenoceptor agonist, AR-C68397XX, in human plasma

A radioimmunoassay has been developed for the determination of AR-C68397XX, a dual D2-receptor and beta2-adrenoceptor agonist, in human plasma. The method incorporates solid phase sample extraction and is suitable for the determination of the analyte at pg ml(-1) concentrations. The antiserum was raised in Suffolk cross sheep following primary and booster immunisations with an immunogen prepared by conjugating a carboxyphenylmethyl derivative of AR-C68397XX, to bovine serum albumin. The radioligand was prepared by the 125I-labelled iodination of a derivative of AR-C68397XX. The solid phase extraction procedure, using octadecyl sorbent, was introduced to remove matrix interferences in the plasma and to enhance method sensitivity. The calibration range is 20-500 pg ml(-1), using 0.5 ml of undiluted human plasma sample.

A radioimmunoassay combined with solid-phase extraction for the determination of a novel anti-obesity agent, ARL 15849XX, in dog plasma.

A radioimmunoassay has been developed for the determination of ARL 15849XX, a cholecystokinin-8 (CCK-8) analogue, in dog plasma. The method incorporates solid-phase sample extraction and is suitable for the determination of the analyte at picogram per millilitre concentrations. The antiserum was raised in Suffolk-cross sheep following primary and booster immunisations with an immunogen prepared by conjugating ARL 16935XX, an analogue of ARL 15849KF, to bovine serum albumin. The radioligand was prepared by the no-carrier-added 125I iodination of a non-sulphated derivative, ARL 15745XX. The solid-phase extraction procedure, carried out using ion-exchange aminopropyl and octadecyl sorbents sequentially, was introduced to remove matrix interferences in the plasma and to enhance the method sensitivity. The calibration range is 20-1000 pg ml-1, using a 1 ml sample of undiluted dog plasma.

A radioimmunoassay combined with solid-phase extraction for the determination (pg ml-1) of AR-C15849XX) in human plasma.

A radioimmunoassay has been developed for the determination of AR-C15849KF, a CCK-8 analogue, in human plasma. The method incorporates solid-phase sample extraction, is suitable for the determination of the analyte at pg ml-1 concentrations and is based on a method developed and validated for dog plasma. The solid-phase extraction, using ion-exchange aminopropyl and octadecyl sorbents sequentially, was retained for this procedure to remove matrix interferences in the plasma and to enhance method sensitivity. The calibration range is 10-500 pg ml-1, using a 1 ml sample of undiluted human plasma. The method has been successfully used to generate early human pharmacokinetic data during a programme of exploratory development.