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Exploration and detection of nitrosamine impurity nitroso-STG-19 in sitagliptin tablets and API as well as nitrites in excipients by LC-MS/MS methods.
Hao, Yajie; Fu, Juan; Wei, Ruixia; Teng, Hao; Yin, Guang; Cao, Qihui; Feng, Zhong; Zhang, Guimin.
Afiliação
  • Hao Y; National Engineering Research Center of Chiral Drugs, Lunan Pharmaceutical Group, Fei County, Linyi, Shandong, China. fengzhong22@163.com.
  • Fu J; National Engineering Research Center of Chiral Drugs, Lunan Pharmaceutical Group, Fei County, Linyi, Shandong, China. fengzhong22@163.com.
  • Wei R; National Engineering Research Center of Chiral Drugs, Lunan Pharmaceutical Group, Fei County, Linyi, Shandong, China. fengzhong22@163.com.
  • Teng H; National Engineering Research Center of Chiral Drugs, Lunan Pharmaceutical Group, Fei County, Linyi, Shandong, China. fengzhong22@163.com.
  • Yin G; National Engineering Research Center of Chiral Drugs, Lunan Pharmaceutical Group, Fei County, Linyi, Shandong, China. fengzhong22@163.com.
  • Cao Q; National Engineering Research Center of Chiral Drugs, Lunan Pharmaceutical Group, Fei County, Linyi, Shandong, China. fengzhong22@163.com.
  • Feng Z; National Engineering Research Center of Chiral Drugs, Lunan Pharmaceutical Group, Fei County, Linyi, Shandong, China. fengzhong22@163.com.
  • Zhang G; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.
Anal Methods ; 16(30): 5288-5295, 2024 Aug 01.
Article em En | MEDLINE | ID: mdl-39018013
ABSTRACT
The Food and Drug Administration (FDA) recently reported a new nitrosamine impurity in sitagliptin that was named nitroso-STG-19 (NTTP), whose acceptable intake limit was extremely low at 37 ng per day. In addition, NTTP was found to be a degradation impurity in sitagliptin tablets, which was formed by the reaction of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride and nitrite salts introduced via excipients. Consequently, the NTTP content in tablets was larger than that in active pharmaceutical ingredients (APIs). To control the impurity, an ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) procedure for the detection of NTTP in sitagliptin phosphate tablets and APIs was developed and validated. Furthermore, a derivatization method for the detection of nitrite salts at lower concentration was developed to select applicable excipients to decelerate the generation of NTTP. During validation of the analytical procedure for NTTP, the quantitation limit (LOQ) of NTTP was 56 ppb (0.056 ng mL-1), the linear correlation coefficient was 0.9998, and recoveries of NTTP in spiked samples ranged from 95.5% to 105.2%, indicating that the method is rapid, sensitive and accurate for an NTTP test. In the nitrite salt detection method, the LOQ was 0.21 ng mL-1, and recoveries of NTTP in spiked samples ranged from 87.6% to 107.8%, indicating a sensitive and accurate method, suitable for screening appropriate pharmaceutical excipients.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Comprimidos / Contaminação de Medicamentos / Excipientes / Espectrometria de Massas em Tandem / Fosfato de Sitagliptina / Nitritos / Nitrosaminas Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Comprimidos / Contaminação de Medicamentos / Excipientes / Espectrometria de Massas em Tandem / Fosfato de Sitagliptina / Nitritos / Nitrosaminas Idioma: En Ano de publicação: 2024 Tipo de documento: Article