Why monitor the presence of nitrosamines in pharmaceutical products?
Chemical reactions between amines, ammonium salts and nitrites, cross-contamination, the use of ingredients already contaminated, packaging, cleaning protocols... the potential sources of nitrosamines are numerous.
Classified or suspected as carcinogenic to humans, European and American markets have repeatedly faced batch recalls of medicines for human use showing traces of nitrosamines.
In 2018, the EMA then launched an investigation and awareness-raising process, supported by the competent authorities, to reduce the risk of nitrosamines being present in pharmaceutical products. In September 2019, the EMA and the CMD published a document entitled "Informations on nitrosamines for marketing autorisation holders" highlighting the importance of assessing the risk of nitrosamine contamination during manufacturing processes.
New requirements were also introduced regarding the responsibilities of MA holders in controlling these impurities, both for active substances and for other components (colorants, solvents, catalysts...).
Our nitrosamine analysis
FILAB laboratory has developed precise and optimized analytical methods to detect and quantify, among others, the following nitrosamines using the technique LC-MSMS :
- NDMA (CAS: 62-75-9)
- NDEA (CAS: 55-18-5)
- NEIPA (CAS: 16339-04-1)
- NDIPA (CAS: 601-77-4)
- NMBA (CAS: 61445-55-4)
- NDBA (CAS: 924-16-3)
- NMPA (CAS: 614-00-6)
- NDPA (CAS: 621-64-7)
- NMEA (10595-95-6)
- NMOR (59-89-2)
- NPYR (930-55-2)
- NPIP (621-64-7)
- NMPEA (13256-11-6)
- NDELA (1116-54-7)
- NDPh/NDPhA (86-30-6)
- MeNP (16339-07-4)
- NMPH (55557-03-4)
- NEPhA (612-64-6)
- NDINA (1207995-62-7)
Detection limits for nitrosamine quantification range between 1 and 10 µk/kg depending on the matrix and nitrosamine.
Targeted analysis of complex nitrosamines:
Non-exhaustive list: 1-Nitroso-4-(2hydroxyethil)-piperazine, 2-Nitroso-octahydrocyclopenta[c]pyrrole, 4-Nitroso-Hydrochloroothiazide, N-Nitroso-Paroxetine, N-Nitroso-Zolmitriptan, N-Nitroso Biotin, N-Nitroso-Folic Acid, N-Nitroso-Clonidine, N-Nitroso-Diclofenac, N-Nitroso-Paroxetine, N-Nitroso-Salbutamol, Posaconazole Nitroso-Impurity 1, Posaconazole Nitroso-Impurity 2
FILAB supports pharmaceutical manufacturers in the research and quantification of nitrosamines
Nitrosamines: what steps should be followed?
In this regard, rapid measures must be taken to carry out a nitrosamine analysis, according to the following steps:
Determination of potential contamination risks by nitrosamines based on production processes
Detailed conclusions on the presence or absence of risks
In its publication, the EMA requested a report on this assessment by a deadline set for March 26, 2020. SWISSMEDIC set this deadline for May 15, 2020.
The analysis methods must be validated
The LOQ must be less than 30 ppb
The analysis must be carried out by a structure compliant with GMP
The authorities must be informed if the results reveal the presence of nitrosamines, regardless of the level.
Our services for nitrosamine analysis and quantification
Quantification of nitrosamines in pharmaceutical products
Nitrosamine Analysis by ATNC
Nitrosamine Analysis by GC-TEA
Method development for nitrosamines : validation and transfer of nitrosamine quantification methods
Contact us for nitrosamine analysis in your pharmaceutical products
If you need a pharmaceutical analysis laboratory for nitrosamine testing in your pharmaceutical products, we can help!
Ensure the compliance and safety of your products with our expert testing services.
Contact us today to discuss your analytical needs and receive a tailored testing solution.
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