N-Nitrosodimethylamine (NDMA) Formation from Ranitidine Impurities : Possible Root Causes of the Presence of NDMA in Ranitidine Hydrochloride
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- Yokoo Hidetomo
- National Institute of Health Sciences Medical Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
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- Yamamoto Eiichi
- National Institute of Health Sciences
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- Masada Sayaka
- National Institute of Health Sciences
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- Uchiyama Nahoko
- National Institute of Health Sciences
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- Tsuji Genichiro
- National Institute of Health Sciences
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- Hakamatsuka Takashi
- National Institute of Health Sciences
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- Demizu Yosuke
- National Institute of Health Sciences
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- Izutsu Ken-ichi
- National Institute of Health Sciences
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- Goda Yukihiro
- National Institute of Health Sciences
書誌事項
- タイトル別名
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- <i>N</i>-Nitrosodimethylamine (NDMA) Formation from Ranitidine Impurities: Possible Root Causes of the Presence of NDMA in Ranitidine Hydrochloride
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<p>N-Nitrosodimethylamine (NDMA) is a probable human carcinogen. This study investigated the root cause of the presence of NDMA in ranitidine hydrochloride. Forced thermal degradation studies of ranitidine hydrochloride and its inherent impurities (Imps. A, B, C, D, E, F, G, H, I, J, and K) listed in the European and United States Pharmacopeias revealed that in addition to ranitidine, Imps. A, C, D, E, H, and I produce NDMA at different rates in a solid or an oily liquid state. The rate of NDMA formation from amorphous Imps. A, C, and E was 100 times higher than that from crystalline ranitidine hydrochloride under forced degradation at 110 °C for 1 h. Surprisingly, crystalline Imp. H, bearing neither the N,N-dialkyl-2-nitroethene-1,1-diamine moiety nor a dimethylamino group, also generated NDMA in the solid state, while Imp. I, as an oily liquid, favorably produced NDMA at moderate temperatures (e.g., 50 °C). Therefore, strict control of the aforementioned specific impurities in ranitidine hydrochloride during manufacturing and storage allows appropriate control of NDMA in ranitidine and its pharmaceutical products. Understanding the pathways of the stability related NDMA formation enables improved control of the pharmaceuticals to mitigate this risk.</p>
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 69 (9), 872-876, 2021-09-01
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390852182141538944
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- NII論文ID
- 130008081978
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- NII書誌ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL書誌ID
- 031643151
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- PubMed
- 34470951
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可