N-nitrosamines are a class of organic compounds having a chemical structure of R2N-N=O. They are normally produced by the reaction of secondary amines and nitrous acid. They can be formed in the compounding of rubber materials and other polymers. N-nitrosamines can also be found as impurities in pharmaceuticals as well as other consumer goods.
Studies have shown that N-nitrosamines can be carcinogenic. The FDA, and other regulatory bodies, have set acceptable daily intake limits for N-nitrosamines.1 If a drug contains levels above the acceptable daily limits, the FDA is requesting that the drug manufacturer recall that drug. Certain drugs used to treat high blood pressure and heart failure known as angiotensin II receptor blockers (ARBs) are among the drugs that the FDA is regulating. Those “-sartan” drugs include, but aren’t limited to: valsartan, losartan and irbesartan.
Here is a list of some N-nitrosamines that SGS Polymer Solutions can test for:
N-Nitrosodimethylamine (NDMA) – Cas. No. 62-75-9
N-Nitrosomethyletylamine (NMEA) – Cas. No. 10595-95-6
N-Nitrosodiethylamine (NDEA) – Cas. No. 55-18-5
N-Nitrosodi-n-propylamine (NDPA) – Cas. No. 621-64-7
N-Nitrosopiperidine (NPIP) – Cas. No. 100-75-5
N-Nitrosopyrrolidine (NPYE) – Cas. No. 930-5-2
N-Nitrodi-n-butylamine (NDBA) – Cas. No. 924-16-3
N-Nitroso-N-methyl-4-aminobutyric Acid (NMBA)- Cas. No. 61445-55-4
Nitrosomorpholine – Cas. No. 59-89-2
SGS Polymer Solutions Incorporated (SGS PSI) has methods for determining several specific N-nitrosamines in pharmaceuticals. We can also provide method validation for your specific material. The testing method most widely used is liquid chromatography with mass spectrometry (LC-MS).
The approach to the testing of N-nitrosamines may need to be a two-step process. If identification of potential N-nitrosamines is needed, SGS PSI can provide screening by gas chromatography with mass spectrometry (GC/MS) or LC-MS. Once they are identified they can then be quantified by LC/MS using the appropriate reference standard. We can reach detection limits in the parts-per-billion. Lower detection limits may be attainable depending upon the polymer matrix and which N-nitrosamine is being quantified. The testing will be performed on our Waters ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometer (UHPLC/Q-TOF-MS).
Contact SGS PSI to discuss your specific N-nitrosamine analysis requirements.