Synthesis and Analysis of isotopically stable labelled Nitrosamines as MS standards for Drug Impurity Quality control.

We describe a simple and easy pathway to synthesize nitrosamine MS standards in good to moderate yields. N-alkylation of Boc-protected primary or secondary amines using stable isotope labelled alkyl halides yielded the key intermediates which were deprotected, and then, the nitrosamine was formed with sodium nitrite and sodium hydrogensulfate. Special attention to safety, disposal of waste, and surface cleaning was carried throughout.