As a player in the pharmaceutical industry, you would like to carry out NDSRI (nitrosamine impurities derived from the active substance) analysis
NDSRI analysis: ensure the compliance of your healthcare products
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
Our HPLC analytical solutions: precision and sensitivity
HPLC-MS/MS
Coupling HPLC with tandem mass spectrometry (Triple Quadrupole) is the method of choice recommended by the EDQM for most NDSRIs (such as N-nitroso-sertraline or N-nitrosoduloxetine).
- Advantages: extremely high selectivity and ultra-low limits of quantification (LOQ).
- Application: routine assays and method validation on complex matrices.
HPLC-HRMS
Using analyzers such as Orbitrap or Q-TOF, this technique is essential for identifying new, unknown impurities.
- Advantages: determination of the exact mass to confirm the molecular structure of the contaminant.
- Application: investigation upon the appearance of an atypical spike or during the R&D phase.
FILAB laboratory assists pharmaceutical manufacturers in the research and quantification of NDSRIs
Increased vigilance in monitoring NDSRI (nitrosamine impurities derived from the active substance)
In an increasingly stringent regulatory environment, Filab laboratory relies on the latest advances from the European General Network of OMCLs (GEON). Impurity monitoring has reached a new stage, moving from classic nitrosamines to the complex detection of NDSRIs.
Since 2018, driven by the European Directorate for the Quality of Medicines (EDQM), detection protocols have become increasingly rigorous. We are integrating the six new reference procedures developed within this framework into our processes.
Why choose FILAB for your nitrosamine analysis?
The FILAB laboratory has developed precise and optimised analysis methods to detect and measure the following nitrosamines, among others, using the LC-MSMS technique:
- 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)
- NMPH (55557-03-4)
- NEPhA (612-64-6)
- NDINA (1207995-62-7)
The limits of detection for determining nitrosamine contents vary from 1 to 10 µk/kg depending on the nitrosamine and matrix being used.
Nitrosamines in IV bags: what does the FDA say and how can we protect ourselves?
Learn moreFAQ
Analysis can be performed on:
- active ingredients (APIs)
- synthetic intermediates
- finished products
Each matrix requires specific preparation and an appropriate analytical strategy.
Yes. The developed methods can be:
- used for exploratory purposes
- validated according to ICH Q2(R2)
- transferred to your internal laboratories or industrial partners
The NDSRI issue can arise:
- during preclinical or clinical development
- during a marketing authorization application
- for a marketed drug
- during a change in process, site, or supplier
The presence of NDSRI can originate from multiple, often combined, sources:
- the chemical structure of the API, which is conducive to nitrosation;
- synthesis or purification steps, particularly in the presence of nitrites or nitrosating agents;
- solvents, reagents, or catalysts used during the process;
- interactions between the API and excipients in the finished product;
- storage conditions (temperature, humidity, duration).
Identifying these potential sources is a key step in NDSRI risk assessment, allowing for targeted analyses and guiding corrective actions if necessary.
