Synthesis of (13C)phenacetin and its application to the breath test for the diagnosis of liver disease.

N-(4-([1-13C]Ethoxy)phenyl)acetamide (13C-phenacetin) was prepared by two methods. In the first method, p-nitrophenol was alkylated with [1-13C]iodoethane and reduced to give 4-([1-13C]ethoxy)aniline (13C-p-phenetidine), which was acetylated with acetic anhydride to give 13C-phenacetin. In the second method, N-acetyl-p-aminophenol was alkylated with [1-13C]iodoethane. By using an excess amount of the starting material, [1-13C]iodoethane was convrted to 13C-phenacetin in high yield. The 13C-phenacetin thus obtained was applied to the breath test, and could be detected by 13CO2 analyzer. Thus, the 13C-phenacetin breath test should be applicable to the diagnosis of liver disease.