JAMA Network: Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions

A study published in JAMA Network titled Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions covers N-nitrosodimethylamine (NDMA), a probable human carcinogen, was recently detected in ranitidine products, prompting widespread regulatory recalls. Ranitidine is a histamine-receptor antagonist that inhibits gastric acid secretion and bears a molecular structure that putatively supports NDMA production under suitable reactive and storage conditions.  We sought to further characterize conditions of NDMA production under simulated physiologic gastric states.

Using LC-HRMS, we detected NDMA formation from ranitidine in SGF across a range of physiologic conditions. At a constant pH of 2.5 and under increasing nitrite concentrations, 150 mg of cool mint branded ranitidine yielded increasing amounts of NDMA after 2 hours: a minimum of 947 ng of NDMA was detected at 1 mmol/L of sodium nitrite and a maximum of 320 000 ng at 50 mmol/L of sodium nitrite (Figure, A). Conversely, holding sodium nitrite constant at 50 mmol/L and varying pH from 1.2 to 5.5 in the presence of 150- or 300-mg ranitidine tablets demonstrated elevated NDMA production under acid conditions (198 000 ng of NDMA at pH 1.2) with diminishing NDMA yields at higher pH (3310 ng at pH 5.5) (Figure, B). Under optimally reactive physiologic conditions (pH 2.5 and 50 mmol/L of sodium nitrite), NDMA yield from a 300-mg ranitidine tablet increased to 0.612 mg (612 000 ng).

Read the full study here.

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JAMA Network: Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions

April 18, 2022

A study published in JAMA Network titled Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions covers N-nitrosodimethylamine (NDMA), a probable human carcinogen, was recently detected in ranitidine products, prompting widespread regulatory recalls. Ranitidine is a histamine-receptor antagonist that inhibits gastric acid secretion and bears a molecular structure that putatively supports NDMA production under suitable reactive and storage conditions.  We sought to further characterize conditions of NDMA production under simulated physiologic gastric states.

Using LC-HRMS, we detected NDMA formation from ranitidine in SGF across a range of physiologic conditions. At a constant pH of 2.5 and under increasing nitrite concentrations, 150 mg of cool mint branded ranitidine yielded increasing amounts of NDMA after 2 hours: a minimum of 947 ng of NDMA was detected at 1 mmol/L of sodium nitrite and a maximum of 320 000 ng at 50 mmol/L of sodium nitrite (Figure, A). Conversely, holding sodium nitrite constant at 50 mmol/L and varying pH from 1.2 to 5.5 in the presence of 150- or 300-mg ranitidine tablets demonstrated elevated NDMA production under acid conditions (198 000 ng of NDMA at pH 1.2) with diminishing NDMA yields at higher pH (3310 ng at pH 5.5) (Figure, B). Under optimally reactive physiologic conditions (pH 2.5 and 50 mmol/L of sodium nitrite), NDMA yield from a 300-mg ranitidine tablet increased to 0.612 mg (612 000 ng).

Read the full study here.

View Other Newsroom Posts

JAMA Network: Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions

A study published in JAMA Network titled Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions covers N-nitrosodimethylamine (NDMA), a probable human carcinogen, was recently detected in ranitidine products, prompting widespread regulatory recalls. Ranitidine is a histamine-receptor antagonist that inhibits gastric acid secretion and bears a molecular structure that putatively supports NDMA production under suitable reactive and storage conditions.  We sought to further characterize conditions of NDMA production under simulated physiologic gastric states.

Using LC-HRMS, we detected NDMA formation from ranitidine in SGF across a range of physiologic conditions. At a constant pH of 2.5 and under increasing nitrite concentrations, 150 mg of cool mint branded ranitidine yielded increasing amounts of NDMA after 2 hours: a minimum of 947 ng of NDMA was detected at 1 mmol/L of sodium nitrite and a maximum of 320 000 ng at 50 mmol/L of sodium nitrite (Figure, A). Conversely, holding sodium nitrite constant at 50 mmol/L and varying pH from 1.2 to 5.5 in the presence of 150- or 300-mg ranitidine tablets demonstrated elevated NDMA production under acid conditions (198 000 ng of NDMA at pH 1.2) with diminishing NDMA yields at higher pH (3310 ng at pH 5.5) (Figure, B). Under optimally reactive physiologic conditions (pH 2.5 and 50 mmol/L of sodium nitrite), NDMA yield from a 300-mg ranitidine tablet increased to 0.612 mg (612 000 ng).

Read the full study here.

A study published in JAMA Network titled Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions covers N-nitrosodimethylamine (NDMA), a probable human carcinogen, was recently detected in ranitidine products, prompting widespread regulatory recalls. Ranitidine is a histamine-receptor antagonist that inhibits gastric acid secretion and bears a molecular structure that putatively supports NDMA production under suitable reactive and storage conditions.  We sought to further characterize conditions of NDMA production under simulated physiologic gastric states.

Using LC-HRMS, we detected NDMA formation from ranitidine in SGF across a range of physiologic conditions. At a constant pH of 2.5 and under increasing nitrite concentrations, 150 mg of cool mint branded ranitidine yielded increasing amounts of NDMA after 2 hours: a minimum of 947 ng of NDMA was detected at 1 mmol/L of sodium nitrite and a maximum of 320 000 ng at 50 mmol/L of sodium nitrite (Figure, A). Conversely, holding sodium nitrite constant at 50 mmol/L and varying pH from 1.2 to 5.5 in the presence of 150- or 300-mg ranitidine tablets demonstrated elevated NDMA production under acid conditions (198 000 ng of NDMA at pH 1.2) with diminishing NDMA yields at higher pH (3310 ng at pH 5.5) (Figure, B). Under optimally reactive physiologic conditions (pH 2.5 and 50 mmol/L of sodium nitrite), NDMA yield from a 300-mg ranitidine tablet increased to 0.612 mg (612 000 ng).

Read the full study here.

View Other Newsroom Posts

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