Analysis and risk assessment of nitrosamines in sartans using GC-MS and Monte Carlo simulation
Abstract The precise detection of nitrosamines at very low levels in various substances is crucial because of their known toxicity and potential to cause genetic mutations. As a result, regulations have been established to evaluate the risk of nitrosamines and manage their presence in pharmaceutical...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-06-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-97844-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849724843987042304 |
|---|---|
| author | Fatemeh Shomali Zahra Talebpour Ghazaleh Abedi Nilufar Mousavi Shiva Mokhtarifar Marjan Kohandani Vahideh Mahdavi Noushin Adib |
| author_facet | Fatemeh Shomali Zahra Talebpour Ghazaleh Abedi Nilufar Mousavi Shiva Mokhtarifar Marjan Kohandani Vahideh Mahdavi Noushin Adib |
| author_sort | Fatemeh Shomali |
| collection | DOAJ |
| description | Abstract The precise detection of nitrosamines at very low levels in various substances is crucial because of their known toxicity and potential to cause genetic mutations. As a result, regulations have been established to evaluate the risk of nitrosamines and manage their presence in pharmaceuticals. In this study, we developed an analytical method involving solvent extraction and gas chromatography-mass spectrometry for the determination of N-nitrosodimethylamine and N-nitrosodiethylamine based on the internal standard method. According to validated results based on ICH guidelines, calibration curves spanned from 2.5 to 40 ng mL−1 with a limit of quantitation of 0.015 µg g−1 for N-nitrosodimethylamine and 0.003 µg g−1 for N-nitrosodiethylamine, meeting the US FDA requirements. The method’s relative recovery was 80–120%, with a relative standard deviation of ≤ 12%. Then, the levels of both nitrosamines were determined using the validated method in 84 samples of active pharmaceutical ingredients or finished products, including valsartan, valsartan methyl ester, sacubitril/valsartan, losartan, and telmisartan. Additionally, we utilized Monte Carlo simulation to assess the potential health risks associated with the use of sartans. According to the obtained results, the Hazard index values were found to be less than 1 indicating that children and adult users may not be at risk of health problems. |
| format | Article |
| id | doaj-art-4f2cac7fc95941a3b4af8a5d011e0d7d |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4f2cac7fc95941a3b4af8a5d011e0d7d2025-08-20T03:10:38ZengNature PortfolioScientific Reports2045-23222025-06-0115111110.1038/s41598-025-97844-0Analysis and risk assessment of nitrosamines in sartans using GC-MS and Monte Carlo simulationFatemeh Shomali0Zahra Talebpour1Ghazaleh Abedi2Nilufar Mousavi3Shiva Mokhtarifar4Marjan Kohandani5Vahideh Mahdavi6Noushin Adib7Department of Analytical Chemistry, Faculty of Chemistry, Alzahra UniversityDepartment of Analytical Chemistry, Faculty of Chemistry, Alzahra UniversityAnalytical and Bioanalytical Research Centre, Alzahra UniversityAnalytical and Bioanalytical Research Centre, Alzahra UniversityDepartment of Analytical Chemistry, Faculty of Chemistry, Alzahra UniversityDepartment of Analytical Chemistry, Faculty of Chemistry, Alzahra UniversityIranian Research Institute of Plant Protection (IRIPP), Agricultural Research, Education and Extension Organization (AREEO)Food and Drug Laboratory Research Center, Food and Drug Administration, Ministry of HealthAbstract The precise detection of nitrosamines at very low levels in various substances is crucial because of their known toxicity and potential to cause genetic mutations. As a result, regulations have been established to evaluate the risk of nitrosamines and manage their presence in pharmaceuticals. In this study, we developed an analytical method involving solvent extraction and gas chromatography-mass spectrometry for the determination of N-nitrosodimethylamine and N-nitrosodiethylamine based on the internal standard method. According to validated results based on ICH guidelines, calibration curves spanned from 2.5 to 40 ng mL−1 with a limit of quantitation of 0.015 µg g−1 for N-nitrosodimethylamine and 0.003 µg g−1 for N-nitrosodiethylamine, meeting the US FDA requirements. The method’s relative recovery was 80–120%, with a relative standard deviation of ≤ 12%. Then, the levels of both nitrosamines were determined using the validated method in 84 samples of active pharmaceutical ingredients or finished products, including valsartan, valsartan methyl ester, sacubitril/valsartan, losartan, and telmisartan. Additionally, we utilized Monte Carlo simulation to assess the potential health risks associated with the use of sartans. According to the obtained results, the Hazard index values were found to be less than 1 indicating that children and adult users may not be at risk of health problems.https://doi.org/10.1038/s41598-025-97844-0NitrosaminesRisk assessmentQuality controlPharmaceuticalGC-MS |
| spellingShingle | Fatemeh Shomali Zahra Talebpour Ghazaleh Abedi Nilufar Mousavi Shiva Mokhtarifar Marjan Kohandani Vahideh Mahdavi Noushin Adib Analysis and risk assessment of nitrosamines in sartans using GC-MS and Monte Carlo simulation Scientific Reports Nitrosamines Risk assessment Quality control Pharmaceutical GC-MS |
| title | Analysis and risk assessment of nitrosamines in sartans using GC-MS and Monte Carlo simulation |
| title_full | Analysis and risk assessment of nitrosamines in sartans using GC-MS and Monte Carlo simulation |
| title_fullStr | Analysis and risk assessment of nitrosamines in sartans using GC-MS and Monte Carlo simulation |
| title_full_unstemmed | Analysis and risk assessment of nitrosamines in sartans using GC-MS and Monte Carlo simulation |
| title_short | Analysis and risk assessment of nitrosamines in sartans using GC-MS and Monte Carlo simulation |
| title_sort | analysis and risk assessment of nitrosamines in sartans using gc ms and monte carlo simulation |
| topic | Nitrosamines Risk assessment Quality control Pharmaceutical GC-MS |
| url | https://doi.org/10.1038/s41598-025-97844-0 |
| work_keys_str_mv | AT fatemehshomali analysisandriskassessmentofnitrosaminesinsartansusinggcmsandmontecarlosimulation AT zahratalebpour analysisandriskassessmentofnitrosaminesinsartansusinggcmsandmontecarlosimulation AT ghazalehabedi analysisandriskassessmentofnitrosaminesinsartansusinggcmsandmontecarlosimulation AT nilufarmousavi analysisandriskassessmentofnitrosaminesinsartansusinggcmsandmontecarlosimulation AT shivamokhtarifar analysisandriskassessmentofnitrosaminesinsartansusinggcmsandmontecarlosimulation AT marjankohandani analysisandriskassessmentofnitrosaminesinsartansusinggcmsandmontecarlosimulation AT vahidehmahdavi analysisandriskassessmentofnitrosaminesinsartansusinggcmsandmontecarlosimulation AT noushinadib analysisandriskassessmentofnitrosaminesinsartansusinggcmsandmontecarlosimulation |