Figure 3. N-Nitrosodimethylamine (NDMA) Formation From Ranitidine at pH 1.2 in Simulated Gastric Fluid and Increasing Nitrite Concentration.

The amount of NDMA formed from a 150-mg ranitidine tablet with various nitrite concentrations under simulated gastric conditions in 50 mL or 250 mL simulated gastric fluid at a pH of 1.2. The values shown are the mean and SD of the 3 independent samples with 2 injections for each sample.

^aThe mean (SD) NDMA levels at 0, 100, 1000, and 5000 μmol/L for a 150-mg tablet in 50 mL simulated gastric fluid were 22 (2) ng, 21 (3) ng, 24 (2) ng, and 24 (3) ng, respectively, representing the background amount of NDMA present in the tablets used for the study within the error of the measurement. There was no detectable amount of NDMA at these levels (limit of detection, 0.33 ng/mL) when a 150-mg tablet was dissolved in 250 mL. Nitrite concentrations less than 100 μmol/L in simulated gastric fluid represent the range of NO₂ amounts observed in clinical studies, with most concentrations being closer to 0 μmol/L than 100 μmol/L.