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; Durişehvar Özer Ünal

Makale detayları

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

Yazarlar:

İbrahim Daniş | Soykan Agar | Mine Yurtsever | Durişehvar Özer Ünal

Yayıncı:

Istanbul University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences (Other)

Dergi:

İstanbul Journal of Pharmacy Vol.54 Issue 3, pp.386-394

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001340670

pISSN:

2587-2087

Anahtar kelimeler:

Özet:

 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 ngmL. The mean r2 value was 0.997 for NDMA and 0.999 for NDEA. For NDMA and NDEA, LOD: 2 ngmL, LOQ: 5 ngmL. 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.

 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 ngmL. The mean r2 value was 0.997 for NDMA and 0.999 for NDEA. For NDMA and NDEA, LOD: 2 ngmL, LOQ: 5 ngmL. 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.

 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 ngmL. The mean r2 value was 0.997 for NDMA and 0.999 for NDEA. For NDMA and NDEA, LOD: 2 ngmL, LOQ: 5 ngmL. 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.

 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 ngmL. The mean r2 value was 0.997 for NDMA and 0.999 for NDEA. For NDMA and NDEA, LOD: 2 ngmL, LOQ: 5 ngmL. 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.

Makale detayları

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

Yazarlar:

İbrahim Daniş | Soykan Agar | Mine Yurtsever | Durişehvar Özer Ünal

Yayıncı:

Istanbul University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences (Other)

Dergi:

İstanbul Journal of Pharmacy Vol.54 Issue 3, pp.386-394

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001340670

pISSN:

2587-2087

DNA binding

molecular docking

MD

mass spectrometry

nitrosamine

NDMA

NDEA

Sayı

Makale detayları

Yazarlar: İbrahim Daniş | Soykan Agar | Mine Yurtsever | Durişehvar Özer Ünal

Yayıncı: Istanbul University

Ana Başlıklar: Pharmacology and Pharmaceutical Sciences (Other)

Dergi: İstanbul Journal of Pharmacy Vol.54 Issue 3, pp.386-394

Belge Tipi: Makale

Yayın Tarihi: 12/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001340670

pISSN: 2587-2087

Sayı

Yazarlar:

İbrahim Daniş | Soykan Agar | Mine Yurtsever | Durişehvar Özer Ünal

Yayıncı:

Istanbul University

Ana Başlıklar:

Pharmacology and Pharmaceutical Sciences (Other)

Dergi:

İstanbul Journal of Pharmacy Vol.54 Issue 3, pp.386-394

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001340670

pISSN:

2587-2087