--- type: "WebPage" title: "Specific analysis and quantification of NDSRI (Nitrosamine Drug Substance Related Impurities)" description: "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 The control of NDSRI impurities (Nitrosamine Drug Substance Related..." resource: "https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/ndsri-nitrosamine-impurities-analysis/" tags: ["EN", "pll_69c39d5c9fd32", "Anaïs DECAUX"] timestamp: "2026-03-25T10:36:00Z" published: "2026-03-25T08:38:18Z" language: "en" author: "Laure Durieux" --- # Specific analysis and quantification of NDSRI (Nitrosamine Drug Substance Related Impurities) ## 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 The control of **NDSRI impurities** (*Nitrosamine Drug Substance Related Impurities*, a regulatory term used by authorities such as the European Medicines Agency) has become a major challenge for the pharmaceutical industry [FILAB](https://filab.fr/en/) laboratory supports pharmaceutical companies in the identification, quantification, and risk management of [nitrosamines](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines.md). We use cutting-edge technologies ([LC-MS/MS](https://filab.fr/en/our-technical-resources/altis-lc-msms-analysis.md) and [LC-HRMS](https://filab.fr/en/our-technical-resources/high-resolution-mass-spectrometry-hrms-analysis.md)) to meet the extremely low detection thresholds imposed by regulatory authorities. NDSRI - (nitrosamine impurities derived from the active substance) ## 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 [Learn more](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/ndsri-nitrosamine-impurities-derived-from-the-active-substance-analysis-laboratory/) ### 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](https://filab.fr/en/our-services/our-expertise-services/life-cycle-of-an-analytical-method-in-the-laboratory/laboratory-analytical-method-validation/validation-of-laboratory-analysis-methods-according-to-the-ich-q2-standard/) on complex matrices. ### HPLC-HRMS Using analyzers such as [Orbitrap](https://filab.fr/en/our-technical-resources/lc-orbitrap-analysis.md) or [Q-TOF](https://filab.fr/en/our-technical-resources/laboratory-for-lc-qtof-analysis.md), 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](https://filab.fr/en/laboratory-mass-spectrometry-unknown-spike-analysis.md) 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](https://filab.fr/en/our-technical-resources/laboratory-analysis-uplc/laboratory-analysis-hplc-lcms.md) technique: - [NDMA (CAS : 62-75-9)](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/laboratory-analysis-ndma.md) - [NDEA (CAS : 55-18-5)](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/laboratory-analysis-ndea.md) - [NEIPA (CAS : 16339-04-1)](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/laboratory-analysis-neipa.md) - [NDIPA (CAS : 601-77-4)](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/laboratory-analysis-ndipa.md) - [NMBA (CAS : 61445-55-4)](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/laboratory-analysis-nmba.md) - [NDBA (CAS : 924-16-3)](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/laboratory-analysis-ndba.md) - [NMPA (CAS : 614-00-6)](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/laboratory-analysis-nmpa.md) - [NDPA (CAS: 621-64-7)](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/laboratory-analysis-of-ndpa-2.md) - NMEA (10595-95-6) - NMOR (59-89-2) - NPYR (930-55-2) - NPIP (621-64-7) - NMPEA (13256-11-6) - [NDELA (1116-54-7)](https://filab.fr/en/our-services/our-analysis-services/laboratory-analysis-nitrosamines/analysis-of-ndela-according-to-iso-10130.md) - 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. Discover our case study ## Nitrosamines in IV bags: what does the FDA say and how can we protect ourselves? [Learn more](https://filab.fr/en/blog/2025/12/nitrosamines-in-infusion-bags-what-does-the-fda-say-and-how-can-you-protect-yourself.md) ## FAQ On what types of samples can NDSRIs be measured? Analysis can be performed on: - active ingredients (APIs) - synthetic intermediates - finished products Each matrix requires specific preparation and an appropriate analytical strategy. Can the methods be validated by regulations? Yes. The developed methods can be: - used for exploratory purposes - validated according to ICH Q2(R2) - transferred to your internal laboratories or industrial partners At what point in the drug lifecycle should the question of NDSRIs be addressed? 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 What are the potential sources of NDSRI formation? 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.