A combined loop-SPE method for the automated preparation of [11C]doxepin

A simple and versatile loop-solid phase extraction (SPE) method was developed for the automated preparation of [C-11]doxepin, a histamine Hi receptor antagonist, from [C-11]methyl triflate ([C-11]MeOTf). This labeling agent was passed through a Teflon or Tefzel loop coated internally with a film of the precursor solution. The reaction products were then flushed from the loop to a short SPE column, where they were concentrated and then injected onto a semi-preparative HPLC column simply by switching an injection valve. By applying this combined loop-SPE technique the whole procedure turned out to be easily automated. The formation of [C-11]methylated doxepin ([C-11]methyldoxepin) was observed and the ratio of doxepin to methyldoxepin was found to be clearly correlated with the mass ratio of nordoxepin to MeOTf. This observation highlights the importance of [C-11]MeOTf specific activity in the [C-11]methylation of secondary amines. Using this method, [C-11]Doxepin was prepared in over 40% radiochemical yield from high specific activity [C-11]MeOTf. Copyright (C) 2002 John Wiley Sons, Ltd.