Foundation, 8-2340 Beerse, BelgiumKetanserin. 3-~2-~4-~4-fluorobenzoyl~-l-piperidinyllethyll-2,4(1H,3H)-quinazolinedione is a new serotonin S2-receptor blocking agent used in hypertension and related diseases. Pharmacokinetic studies required the synthesis of monolabelled 3H-and 14C-ketanserin tartrate. The tritium compound had the label placed at the fluorobenzoyl moiety, whereas for 14C-ketanserin the heterocyclic part of the quinazolinedione system was chosen. Receptor binding studies and application in radioimunoassay necessitated the synthesis of a molecule at higher specific activity, hence a dilabelled molecule was constructed with tritium atoms placed at opposite positions in the molecule. The title compounds were obtained at specific activities of 169.5, 4.66 and 34900 mCi/mmol, respectively and with HPLC purities of > 98%.

Lorcainide, a new antiarrhythmic agent currently undergoing clinical trial, has been pentadeuterated and the usefulness of this labelled compound in pharmacokinetic and metabolism studies has been investigated in dogs. Specific analytical methods based on capillary gas chromatography/mass spectrometry (GC/MS) were developed for quantitative and qualitative analysis of plasma and urine samples. Following oral administration of an equimolar mixture of 5 : 5 mg of (2H0/2H5)lorcainide, eight major metabolites were rapidly identified in urine by the ion cluster technique. Quantitative analysis of (2H0/2H5)lorcainide in plasma and urine indicated an enhanced systematic availability of the deuterated compound, probably due to a secondary isotope effect. According to these findings in the dog, the use of deuterated lorcainide in human bioavailability and metabolism studies is probably of limited value.

Ritanserin, a new selective serotonin-S2 antagonist, was labelled in one 4-fluorophenyl moiety to obtain a (2H4)-labelled analogue having the following isotopic distribution: 2H0: 0.0%, 2H1: 0.1%, 2H2: 1.9%, 2H3: 5.8%, 2H4: 92.2%. (2H0/2H4) Ritanserin and the internal standard were isolated from the plasma by liquid/liquid extraction and analysed by selected-ion monitoring gas chromatography/mass spectrometry in the 70 eV electron impact mode. A detection limit of 0.1 ng ml-1 could be obtained for both (2H0) and (2H4)ritanserin. The precision (per cent coefficient of variation) and accuracy (per cent relative error) of the method were 4.1% and 4.1%, respectively. The method was used to determine the plasma levels of ritanserin and tetradeuterated ritanserin in three healthy male subjects receiving an equimolar mixture of 5:5 mg (2H0/2H4)ritanserin. The pharmacokinetics of both isotopomers proved to be identical, indicating the absence of an isotope effect, so that this technique might be very promising for use in bioequivalence studies.

S Pounds [PerkinElmer Life and Analytical Sciences, Inc., USA]—Preparation of carrier – free [Methyl‐3H] Methyl Nosylate and its Use as a Radiochemically Stable Methylating reagent. DJ Wilkinson, AN Mather, MJ Hickey, LP Kingston [Astra Zeneca, UK]—Tritio‐Dehalogenation: New Variants on an Old Theme. VG Sidorov, YB Zverkov, NF Myasoedov, IMG, Russia; IL Karpenko, EA Shirokova, DM Yanvarev, MV Yasko, YS Skoblov [EIMB, Russia], AB Susan, [IICH, USA]—The Syntheses of Labeled 3 ‘‐Azido‐3’‐Deoxythymidine Derivatives Displaying Anti‐HIV Activity. NF Myasoedov, IY Nagaev, VP Shevchenko [IMG, Russia], AB Susan [IICH, USA], G Rotert [Abbott, USA]—Synthesis of Radiolabeled [3H]ABT‐578 for ADME Studies. J Krueger, E Linnemann, G Fels [University of Paderborn, Germany]—(‐)‐[3H]Galanthamine – Labelling, Derivatization, and Application as Photoaffinity Probe. F Wuest [Research Centre Rossendorf, Germany]—Carbon‐11 Labeled Compounds in the Development of Pharmaceuticals. P Maeding, J Zessin, F Wüst [Research Centre Rossendorf, Germany], U Pleiss [Bayer HealthCare AG, Germany]—11C‐Labeling of a Taxane Derivative by [1‐11C] Acetylation. J Bloom [Amersham Biosciences, UK]—The Preparation of 2‐Methyl [ring‐2‐14C] benzyl chloride. V Derdau, R Oekonomopulos, G Schubert, H Heitsch [Aventis Pharma Deuschland GmbH, Germany]—Synthesis of 14C Labeled Angiotensin‐(1‐7)‐Receptor Agonist AVE 0991. H Andres, P Burtscher, Y Metz, T Moenius [Novartis Pharma AG, Switzerland]—C‐14 Labeling of the β‐Amino Carboxyl Moiety–Alternatives to the Acrylate Approach. F Kaegi, Y Metz, I Rodriguez, R Ruetsch [Novartis Pharma AG, Switzerland]—Effective Carbon‐14 Labelling under Microwave Irradiation. CGM Janssen, B Verreet, HAC Lenoir, JBA Thijssen [Johnson & Johnson, Belgium]—Stable Isotope Labeled Compounds as Internal Standards for LC‐MS/MS, Requirements and Some Synthetic Approaches. RP Stuerm [SafPro AG, Switzerland]—Models for Calculating the Radiation Dose after Incorporation of 3H and 14C. A. Krins [VKTA Nuclear Engineering and Analytics e.V., Germany]—Dosimetry of C‐14 Labeled Organic Compounds. E Rausch [Raytest GmbH, Germany], M Breyer, K Hucke, D Gaefke, K Schmeer [Bayer HealthCare AG, Germany]—A New Option of 14C‐Detection in Combination with Micro HPLC.