Synthesis of [formula omitted] by using multivariate strategies for optimization of radiochemical yields

Abstract

The synthesis of N-[ methyl- 11C] hydromorphone has been performed by using [ 11C]methyl iodide and desmethyl hydromorphone in a mixture of dimethylsulphoxide and dimethylformamide as solvent. Optimization of the radiochemical yield by varying the reaction conditions was performed by using multivariate strategies [Box et al. Statistics for Experiments (Wiley, New York, 1978); (1) Dean and Heald Science 189, 805 (1975); (2) Carlsson et al. Acta Chem. Scand. B7, 9 (1983); (3) Spendley et al. Technometrics 4, 441 (1962) (4)], such as simplex (4) and the response surface method RSREG in SAS (Statistical Analytical System) [SAS-version 5; available from SAS Institute Inc., Box 8000, Cary, NC 27511-8000, U.S.A. (5). The labelled hydromorphone was obtained in 72% radiochemical yield in the alkylation reaction with [ 11C]methyl iodide, counted from the end of the [ 11C]methyl iodide synthesis. N-[ Methyl- 11C] hydromorphone was obtained as a ready injectable pharmaceutical solution with a total synthesis time of 40 min and in a 10% total radiochemical yield, with a radiochemical purity >99.5%, according to HPLC analysis.