The synthesis of labelled forms of saquinavir

The development of the HIV-protease inhibitor, saquinavir (Ro 31-8959), req uired a range of analytical methods for the measurement of the parent drug and drug-related material in biological fluids. This paper describes the sy nthesis of 14-carbon and tritium labelled compounds used for in vivo and in vitro investigations of the absorption and disposition of saquinavir in an imals and man. It also discusses the preparation of saquinavir labelled wit h deuterium and stable isotopes of carbon and nitrogen. These forms of the drug were needed for bioequivalence studies in which HPLC/MS/MS was employe d for the measurement of plasma concentrations. Finally, the synthesis of a 125-iodine labelled tracer used in a radioimmunoassay for saquinavir is de scribed.