Tritium labelling of bromhexine via amide reduction with LiB³H₄

The mucolytic agent bromhexine is useful in the evaluation of the performance of inductively coupled plasma mass spectrometry (ICP-MS) as compared to radiolabelling. A prerequisite for this comparison is access to radiolabelled bromhexine. [³H₂]-bromhexine was synthesized in three steps introducing tritium in the final step by reduction of 2-amino-3,5-dibromo-N-methyl-N-cyclohexylbenzamide. Good chemical yields, high specific activity (54Ci/mmol) and high radiochemical purity (98.5%) were achieved. Reduction with LiB³H₄ in dichloromethane proved to be very efficient and easy to handle.