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

A simple and versatile loop‐solid phase extraction (SPE) method was developed for the automated preparation of [ 11 C]doxepin, a histamine H 1 receptor antagonist, from [ 11 C]methyl triflate ([ 11 C]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 [ 11 C]methylated doxepin ([ 11 C]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 [ 11 C]MeOTf specific activity in the [ 11 C]methylation of secondary amines. Using this method, [ 11 C]Doxepin was prepared in over 40% radiochemical yield from high specific activity [ 11 C]MeOTf. Copyright © 2002 John Wiley & Sons, Ltd.