Synthesis of USP Grade [2,3,7-¹³C₃]-Nicotinamide for Human Pharmacokinetic Studies

[2,3,7-¹³C₃]-nicotinamide has been prepared in five synthetic steps and purified to > 99% homogeneity, meeting United States Pharmacopeia (USP) standards for oral pharmaceutical dosing. We prepared 17.8 g with an overall synthetic yield of 42%. The labeled atoms are strategically placed to resist removal by known metabolic reactions. The NMR spectral features of the ¹³C-labeled nicotinamide are presented and discussed in detail. We also demonstrate that three heavy atoms are sufficient to achieve > 1000:1 mass spectral signal resolution in mixtures with naturally occurring, unlabeled nicotinamide. This material is intended for pharmacokinetic studies in human volunteers.