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 [¹¹C]doxepin, a histamine H₁ receptor antagonist, from [¹¹C]methyl triflate ([¹¹C]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 [¹¹C]methylated doxepin ([¹¹C]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 [¹¹C]MeOTf specific activity in the [¹¹C]methylation of secondary amines. Using this method, [¹¹C]Doxepin was prepared in over 40% radiochemical yield from high specific activity [¹¹C]MeOTf.