Analysis of an Impurity, N-Nitrosodimethylamine, in Valsartan Drug Substances and Associated Products Using GC-MS
Autor: | Ryoko Arai, Takashi Hakamatsuka, Ken-ichi Izutsu, Genichiro Tsuji, Nahoko Uchiyama, Haruhiro Okuda, Yukihiro Goda, Yosuke Demizu, Yasuhiro Abe, Hiroshi Akiyama, Sayaka Masada, Tomoaki Tsutsumi |
---|---|
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Pharmacology Detection limit Drug Chromatography Chemistry media_common.quotation_subject Relative standard deviation Pharmaceutical Science General Medicine Contamination 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Valsartan Impurity N-Nitrosodimethylamine 030220 oncology & carcinogenesis medicine Gas chromatography–mass spectrometry medicine.drug media_common |
Zdroj: | Biological and Pharmaceutical Bulletin. 42:547-551 |
ISSN: | 1347-5215 0918-6158 |
Popis: | Valsartan products, commonly used to treat high blood pressure and heart failure, have been recalled in many countries due to the presence of an impurity, N-nitrosodimethylamine (NDMA), in the recalled products. We present and evaluate a GC-MS-based analytical method for the determination of NDMA levels and attempt an investigation of NDMA concentrations in valsartan drug substances and associated products. The limit of detection and limit of quantification for the method were estimated to be 0.1 and 0.5 µg/g, respectively, when testing a 0.5-g sample. A good trueness (99%) with a small relative standard deviation (1.9%) was obtained for a valsartan product spiked with NDMA at a concentration of 1.0 µg/g. Additionally, a valsartan drug substance and the associated product, which were previously determined to have NDMA contamination, were analyzed by the method. The NDMA content by our method was very close to previously determined values. Finally, six samples, including valsartan drug substances and associated, commercially available products in Japan, all of which were derived from the company implicated in the NDMA contamination, were analyzed by our method, revealing that none of these samples contained detectable concentrations of NDMA. Overall, the data indicate that the present method is reliable and useful for determination of NDMA in valsartan drug substances and associated products. |
Databáze: | OpenAIRE |
Externí odkaz: |