İstanbul Journal of Pharmacy

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DOI :10.26650/IstanbulJPharm.2024.1500047   IUP :10.26650/IstanbulJPharm.2024.1500047    Tam Metin (PDF)

High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application

İbrahim Daniş, Soykan Agar, Mine Yurtsever, Duri Şehvar Ünal

Background and Aims: Nitrosamines are amine compounds attached to a nitroso group. The reaction of amines and nitrosating agents forms nitrosamines. Nitrosamine impurities are classified as Class 1 based on the carcinogenicity and mutagenicity data by ICH M7 (R1). The recent discovery of nitrosamines in some pharmaceutical products has caused concern. Nitrosamines are carcinogenic, so it is necessary to determine the possible nitrosamines in pharmaceutical products.

Methods: An Inertsil ODS-3, (4.6x250 mm, 5 μm) column was used for separation. A triple quadrupole mass detector with electrospray Ionisation (ESI) was used for detection. Multiple reaction monitoring (MRM) was used for quantification. The transition ions are 75.1 > 43.3 for NDMA and 103.0 > 75.1 for NDEA. The calibration curves consist of 5 concentration levels, including NDMA and NDEA (5, 10, 50, 100, 150 ng/mL). The mean r2 value was 0.997 for NDMA and 0.999 for NDEA. For NDMA and NDEA, LOD: 2 ng/mL, LOQ: 5 ng/mL.

Results: Comprehensive in silico and in vitro results indicate that the method has good accuracy and precision

Conclusion: DNA binding interactions of the molecules NDMA and NDEA, were investigated through the molecular docking and molecular dynamics methods. Molecular Docking simulations showed that these small organic molecules have high-affinity scores and strongly bind to the minor groove of the hDNA via strong hydrogen bonds. 

Anahtar Kelimeler: DNA binding, molecular docking, MD, mass spectrometry, nitrosamine, NDMA, NDEA

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APA

Daniş, İ., Agar, S., Yurtsever, M., & Ünal, D. (2024). High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application. İstanbul Journal of Pharmacy, 54(3), 386-394. https://doi.org/10.26650/IstanbulJPharm.2024.1500047


AMA

Daniş İ, Agar S, Yurtsever M, Ünal D. High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application. İstanbul Journal of Pharmacy. 2024;54(3):386-394. https://doi.org/10.26650/IstanbulJPharm.2024.1500047


ABNT

Daniş, İ.; Agar, S.; Yurtsever, M.; Ünal, D. High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application. İstanbul Journal of Pharmacy, [Publisher Location], v. 54, n. 3, p. 386-394, 2024.


Chicago: Author-Date Style

Daniş, İbrahim, and Soykan Agar and Mine Yurtsever and Duri Şehvar Ünal. 2024. “High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application.” İstanbul Journal of Pharmacy 54, no. 3: 386-394. https://doi.org/10.26650/IstanbulJPharm.2024.1500047


Chicago: Humanities Style

Daniş, İbrahim, and Soykan Agar and Mine Yurtsever and Duri Şehvar Ünal. “High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application.” İstanbul Journal of Pharmacy 54, no. 3 (Mar. 2025): 386-394. https://doi.org/10.26650/IstanbulJPharm.2024.1500047


Harvard: Australian Style

Daniş, İ & Agar, S & Yurtsever, M & Ünal, D 2024, 'High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application', İstanbul Journal of Pharmacy, vol. 54, no. 3, pp. 386-394, viewed 14 Mar. 2025, https://doi.org/10.26650/IstanbulJPharm.2024.1500047


Harvard: Author-Date Style

Daniş, İ. and Agar, S. and Yurtsever, M. and Ünal, D. (2024) ‘High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application’, İstanbul Journal of Pharmacy, 54(3), pp. 386-394. https://doi.org/10.26650/IstanbulJPharm.2024.1500047 (14 Mar. 2025).


MLA

Daniş, İbrahim, and Soykan Agar and Mine Yurtsever and Duri Şehvar Ünal. “High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application.” İstanbul Journal of Pharmacy, vol. 54, no. 3, 2024, pp. 386-394. [Database Container], https://doi.org/10.26650/IstanbulJPharm.2024.1500047


Vancouver

Daniş İ, Agar S, Yurtsever M, Ünal D. High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application. İstanbul Journal of Pharmacy [Internet]. 14 Mar. 2025 [cited 14 Mar. 2025];54(3):386-394. Available from: https://doi.org/10.26650/IstanbulJPharm.2024.1500047 doi: 10.26650/IstanbulJPharm.2024.1500047


ISNAD

Daniş, İbrahim - Agar, Soykan - Yurtsever, Mine - Ünal, Duri Şehvar. “High Performance Liquid Chromatography-Tandem Mass Spectrometric determination of carcinogen nitrosamine impurities from pharmaceuticals and DNA binding confirmation aided by molecular docking application”. İstanbul Journal of Pharmacy 54/3 (Mar. 2025): 386-394. https://doi.org/10.26650/IstanbulJPharm.2024.1500047



ZAMAN ÇİZELGESİ


Gönderim13.06.2024
Kabul16.10.2024
Çevrimiçi Yayınlanma30.12.2024

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