Participants were given 2 mg of orally administered deuterium-labeled cotinine (cotinine-d4) solution (30). Eight hours post cotinine administration, a saliva sample was obtained from the participants for measurement of the cotinine-d4 and deuterium-labeled 3’-hydroxycotinine (3HC-d4). Cotinine-d4 and 3HC-d4 were measured using liquid chromatography-tandem mass spectrometry (32). The NMR was then calculated from the 8-hour salivary sample using the deuterium-labeled 3HC (3HC-d4) to cotinine-d4 ratio (27).