İlaçlardaki nitrozamin safsızlıklarının belirlenmesi
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Dosyalar
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
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Yayıncı
Hatay Mustafa Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Nitrozaminler son zamanlarda ilaçlarda tespit edilen son derece zararlı kanserojen, mutajenik ve teratojenik safsızlıklardır. Bu safsızlıklar, üretim sürecinde kullanılan reaktif, katalizör, çözücü veya ham maddeler yoluyla oluşarak ilaç maddelerine dahil olabildikleri gibi, ilaçlar üretildikten sonra da saklama koşullarına, ambalaj malzemelerine ve aktif maddelerin bozunma süreçlerine bağlı olarak da oluşabilmektedirler. Bu çalışmada, sartan etken maddesine sahip olan ilaçların N-nitrosodimetil amin (NDMA) ve N-nitrosodietil amin (NDEA) içerikleri, headspace GC-MS aracılığıyla belirlenmiştir. En yüksek NDMA konsantrasyonları losartan (67.05 mg kg-1) etken maddesine sahip olan ilaçlarda, en yüksek NDEA konsantrasyonları ise kandesartan (22.48 mg kg-1) ve olmesartan (20.13 mg kg-1) etken maddelerine sahip olan ilaçlarda saptanmıştır. Her bir tabletteki NDMA miktarları 3.6.10-4 – 1.7.10-2 mg arasında ve NDEA miktarları da 3.3.10-4 – 8.8.10-3 mg arasında tespit edilmiştir. Elde edilen değerler kabul edilebilir alım limitlerinin (NDMA için 96 ng/gün ve NDEA için 26.5 ng/gün) üzerinde bulunmuştur.
Nitrosamines are extremely harmful carcinogenic, mutagenic and teratogenic impurities that have been detected in drugs recently. These impurities can be included in the drug substances by being formed by the reagents, catalysts, solvents or raw materials used in the production process, or they can also occur after the drugs are produced, depending on the storage conditions, packaging materials and the decomposition processes of the active substances. In this study, N-nitrosodimethyl amine (NDMA) and N-nitrosodiethyl amine (NDEA) contents of drugs with sartan active ingredient were determined by headspace GC-MS. The highest NDMA concentrations were found in drugs with losartan (67.05 mg kg-1) active ingredient, and the highest NDEA concentrations in drugs with active ingredients candesartan (22.48 mg kg-1) and olmesartan (20.13 mg kg-1). The amounts of NDMA in each tablet were found to be between 3.6.10-4 – 1.7.10-2 mg and the amounts of NDEA between 3.3.10-4 – 8.8.10-3 mg. The values obtained were above the acceptable intake limits (96 ng/day for NDMA and 26.5 ng/day for NDEA).
Nitrosamines are extremely harmful carcinogenic, mutagenic and teratogenic impurities that have been detected in drugs recently. These impurities can be included in the drug substances by being formed by the reagents, catalysts, solvents or raw materials used in the production process, or they can also occur after the drugs are produced, depending on the storage conditions, packaging materials and the decomposition processes of the active substances. In this study, N-nitrosodimethyl amine (NDMA) and N-nitrosodiethyl amine (NDEA) contents of drugs with sartan active ingredient were determined by headspace GC-MS. The highest NDMA concentrations were found in drugs with losartan (67.05 mg kg-1) active ingredient, and the highest NDEA concentrations in drugs with active ingredients candesartan (22.48 mg kg-1) and olmesartan (20.13 mg kg-1). The amounts of NDMA in each tablet were found to be between 3.6.10-4 – 1.7.10-2 mg and the amounts of NDEA between 3.3.10-4 – 8.8.10-3 mg. The values obtained were above the acceptable intake limits (96 ng/day for NDMA and 26.5 ng/day for NDEA).
Açıklama
Anahtar Kelimeler
Kimya, Chemistry
