DETERMINATION OF N-NITROSODIMETHYL AMINE (NDMA) AND N-NITROSODIETHYL AMINE (NDEA) IN MEDICINES CONTAINING SARTAN AND ITS DERIVATIVES

Year 2024, Volume: 48 Issue: 3, 1118 - 1127, 10.09.2024

Şana Sungur , Muhammed Aljoubasi , Zeki Aydın

https://doi.org/10.33483/jfpau.1436182

Abstract

Objective: In this study, it was aimed to determine the amounts of N-nitrosodimethyl amine (NDMA) and N-nitrosodiethyl amine (NDEA) in drugs containing sartan and its derivatives.
Material and Method: Medicines containing sartan and its derivatives as active ingredients such as valsartan, losartan, telmisartan, olmesartan, candesartan, irbesartan were purchased from pharmacies. NDMA and NDEA amounts of drugs were determined by headspace GC-MS.
Result and Discussion: The highest NDMA concentrations were found in drugs with losartan active ingredient (67.05±0.15mg kg-1), and the highest NDEA concentrations were found in drugs with candesartan (22.48±0.06 mg kg-1) and olmesartan (20.13 ± 0.06 mg kg-1) active ingredient. The NDMA contents in each tablet were between 3.6x10-4- 1.7x10-2 mg and the NDEA contents were between 3.3x10-4 – 8.8x10-3 mg. The acceptable daily intake limits specified by the European Medicines Agency and the Food and Drug Administration are 96 ng/day for NDMA and 26.5 ng/day for NDEA. It was observed that the values obtained were above the acceptable intake limits even if one tablet was taken per day.

Keywords

Drug, headspace GC-MS, N-nitrosodiethyl amine (NDEA), N-nitrosodimethyl amine (NDMA), sartan

Ethical Statement

Etik belgesi gerekmemektedir.

Supporting Institution

Hatay Mustafa Kemal University

Project Number

22.YL.014

Thanks

This research (22.YL.014) was supported by the Scientific Research Projects Coordination Unit of Hatay Mustafa Kemal University. The authors would like to thank the Scientific Research Projects Coordination Unit of Hatay Mustafa Kemal University for financial support.

SARTAN VE TÜREVLERİNİ İÇEREN İLAÇLARDA N-NİTROSODİMETİL AMİN (NDMA) VE N-NİTROSODİETİL AMİN (NDEA) TAYİNİ

Abstract

Amaç: Bu çalışmada, sartan ve türevlerini içeren ilaçların N-nitrosodimetil amin (NDMA) ve N-nitroso dietil amin (NDEA) miktarlarının belirlenmesi amaçlanmıştır.
Gereç ve Yöntem: Etken madde olarak valsartan, losartan, telmisartan, olmesartan, kandesartan, irbesartan gibi sartan ve türevlerini içeren ilaçlar eczanelerden satın alınmıştır. İlaçların NDMA ve NDEA miktarları headspace GC-MS ile belirlenmiştir.
Sonuç ve Tartışma: En yüksek NDMA konsantrasyonu losartan etken maddeli ilaçlarda (67.05 ± 0.15 mg kg-1), en yüksek NDEA konsantrasyonu ise kandesartan (22.48±0.06 mg kg-1) ve olmesartan (20.13 ± 0.06 mg kg-1) etken maddeli ilaçlarda bulunmuştur. Her tabletteki NDMA içerikleri 3.6x10-4-1.7x10-2 mg arasında, NDEA içerikleri ise 3.3x10-4- 8.8x10-3 mg arasında saptanmıştır. Avrupa İlaç Ajansı ve Gıda ve İlaç İdaresi tarafından belirlenen kabul edilebilir. Günlük alım limitleri NDMA için 96 ng/gün ve NDEA için 26.5 ng/gündür. Elde edilen değerlerin günde bir tablet alınsa bile kabul edilebilir alım limitlerinin üzerinde olduğu görülmüştür.

Keywords

Headspace GC-MS, ilaç, N-nitrosodietil amin (NDEA), N-nitrosodimetil amin (NDMA), sartan

Project Number

22.YL.014

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