Formation of nitrosamines is possible in the presence of secondary, tertiary, or quaternary amines22 and nitrite salts23 under acidic reaction conditions. Under these conditions, nitrite salts may form nitrous acid, which can react with an amine to form a nitrosamine (see Figure 1).
What is the limit of nitrosamine impurities?
Acceptable intake limits
If more than one nitrosamine impurity is detected and the total quantity of nitrosamine impurities exceeds 26.5 ng/day (the acceptable intake for the most potent nitrosamines) based on the maximum daily dose (MDD), the FDA requests that the manufacturer contact the agency for evaluation.
What foods are high in nitrosamines?
Foods which have been shown to contain volatile nitrosamines include cured meats, primarily cooked bacon; beer; some cheeses; nonfat dry milk; and sometimes fish. It should be emphasized that not all samples analyzed contain detectable amounts of nitrosamines.
How do you reduce nitrosamine?
If you drink well water, your local health department can help you find out if this is a problem in your area. You can also have your water tested by a laboratory. Eat a diet high in antioxidants. Vitamin C and certain other vitamins can reduce the conversion of nitrates and nitrites to nitrosamines.
What drugs contain nitrosamine?
Some of these drugs from certain manufacturers – including angiotensin II receptor blockers (ARBs), ranitidine, nizatidine, and metformin – have been recalled because of nitrosamine impurities. The FDA has requested manufacturers withdraw all ranitidine (brand name Zantac) products on the U.S. market.
Are nitrosamines harmful?
Nitrates and nitrites are essential compounds, but they can become hazardous if they form nitrosamines. Nitrosamines can form if you cook nitrates or nitrites at high heat. (25). There are different types of nitrosamines, and many can increase the risk for cancer.
Is nitrosamine a carcinogen?
Nitrosamines form a large group of genotoxic chemical carcinogens which occur in the human diet and other environmental media, and can be formed endogenously in the human body. N-Nitroso compounds can induce cancer in experimental animals.
What is nitrosamine contamination?
Nitrosamine impurities formed during the processing of active pharmaceuticals ingredients (APIs) under certain processing conditions and with certain raw materials, starting materials, and intermediates present.
Why is NDMA in metformin?
Metformin is a common medication used to treat high blood sugar in those with type 2 diabetes. NDMA is a nitrosamine impurity that is also referred to as N-nitrosodimethylamine. This impurity is thought to cause cancer.
What is nitrosamine risk assessment?
Based on ICH M7 (R1), Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, N-Nitrosamines are compounds of concern due to their mutagenic carcinogenic effect. Hence, they are to be controlled at or below the acceptable cancer risk levels.
What is meant by genotoxic impurities?
Per the International Council for Harmonization (ICH) S2 (R1) Guideline, genotoxic impurities can be broadly defined as impurities that have been demonstrated to cause deleterious changes in the genetic material regardless of the mechanism.
How are nitrosamines carcinogenic?
Nitrosamines are not directly carcinogenic. Metabolic activation is required to convert them to the alkylating agents that modify bases in DNA, inducing mutations. The specific alkylating agents vary with the nitrosamine, but all are proposed to feature alkyldiazonium centers.
How does N nitrosamines cause DNA damage?
Nitrosamines exert their toxic and mutagenic effects by alkylating N-7 of guanine, leading to destabilization and increased breakage of DNA .
Do cigarettes contain nitrosamines?
Tobacco-specific nitrosamines (TSNAs) are thought to be some of the most potent carcinogens in tobacco products. They are unique to tobacco and present in smokeless tobacco, snuff, cigarettes, and electronic cigarette liquid.
Does vitamin C prevent nitrosamine formation?
Nitrosamines are formed in acidic conditions, such as those afforded by stomach acid, but vitamin C inhibits their formation, by converting nitrite to nitric oxide.
Which vitamin prevents the formation of nitrosamine?
Vitamin E and selenium have been found to minimize or prevent the reaction of nitrites/nitrates with amines and hence prevent or reduce the formation of carcinogenic nitrosamines. Vitamin C (ascorbic acid) is known to inhibit nitrosamine formation.
How do you test for nitrosamines?
To help test these products for the presence of nitrosamines, CDER scientists have developed and publicly shared multiple methods,2 including gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-MS (LC-MS) technologies, specific for detecting and quantifying up to eight different nitrosamines in these …
Are nitrosamines polar?
Since the nitrosamines are relatively polar organic compounds, a liquid-liquid extraction was employed for fat-rich food samples. Acetone-water (3 : 1) or acetone-acetonitrile mixture satisfied the terms.
What do nitrites in urine mean?
Normal urine contains chemicals called nitrates. If bacteria enter the urinary tract, nitrates can turn into different, similarly named chemicals called nitrites. Nitrites in urine may be a sign of a urinary tract infection (UTI). UTIs are one of the most common types of infections, especially in women.
Do Trojan condoms have nitrosamines?
And certain varieties of the major condom brands, including Trojan, Durex and Lifestyles, also are nitrosamine free.
Why is NDMA in food?
NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables. The FDA has been investigating NDMA and other nitrosamine impurities in blood pressure and heart failure medicines called Angiotensin II Receptor Blockers (ARBs) since last year.
How did NDMA get into Zantac?
Apparently, the way NDMA got into Zantac was not through a manufacturing process, but rather was due to Zantac’s unstable nature. Based on the results of laboratory tests, NDMA has been classified as a potential human carcinogen, or a substance that can cause cancer.
Has Zantac always had NDMA in it?
NDMA was present in both the finished drug product samples and the active pharmaceutical ingredients (APIs) that the FDA tested. … However, the FDA’s recent laboratory testing results demonstrate that levels of NDMA in some ranitidine finished drug products increase over time at room temperature.