Journal of chromatography. A 2014-09-26

Determination of trace level genotoxic impurities in small molecule drug substances using conventional headspace gas chromatography with contemporary ionic liquid diluents and electron capture detection.

Tien D Ho, Peter M Yehl, Nik P Chetwyn, Jin Wang, Jared L Anderson, Qiqing Zhong

文献索引:J. Chromatogr. A. 1361 , 217-28, (2014)

全文:HTML全文

摘要

Ionic liquids (ILs) were used as a new class of diluents for the analysis of two classes of genotoxic impurities (GTIs), namely, alkyl/aryl halides and nitro-aromatics, in small molecule drug substances by headspace gas chromatography (HS-GC) coupled with electron capture detection (ECD). This novel approach using ILs as contemporary diluents greatly broadens the applicability of HS-GC for the determination of high boiling (≥ 130°C) analytes including GTIs with limits of detection (LOD) ranging from 5 to 500 parts-per-billion (ppb) of analytes in a drug substance. This represents up to tens of thousands-fold improvement compared to traditional HS-GC diluents such as dimethyl sulfoxide (DMSO) and dimethylacetamide (DMAC). Various ILs were screened to determine their suitability as diluents for the HS-GC/ECD analysis. Increasing the HS oven temperatures resulted in varying responses for alkyl/aryl halides and a significant increase in response for all nitroaromatic GTIs. Linear ranges of up to five orders of magnitude were found for a number of analytes. The technique was validated on two active pharmaceutical ingredients with excellent recovery. This simple and robust methodology offers a key advantage in the ease of method transfer from development laboratories to quality control environments since conventional validated chromatographic data systems and GC instruments can be used. For many analytes, it is a cost effective alternative to more complex trace analytical methodologies like LC/MS and GC/MS, and significantly reduces the training needed for operation.Copyright © 2014 Elsevier B.V. All rights reserved.


相关化合物

  • 二甲基亚砜
  • 溴化苄
  • 邻硝基苯甲醛
  • 1-硝基萘
  • 三氯甲苯
  • 杀鼠灵
  • 对硝基苯甲醛
  • 2-氯-5-硝基苯胺
  • 邻氯硝基苯
  • 2,4-二甲基硝基苯

相关文献:

The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells.

2015-01-01

[Drug Des. Devel. Ther. 9 , 1627-52, (2015)]

Activation of Tomato Bushy Stunt Virus RNA-Dependent RNA Polymerase by Cellular Heat Shock Protein 70 Is Enhanced by Phospholipids In Vitro.

2015-05-01

[J. Virol. 89(10) , 5714-23, (2015)]

Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial-mesenchymal transition and fibrosis during peritoneal dialysis.

2015-01-01

[EMBO Mol. Med. 7(1) , 102-23, (2015)]

Inducible, tightly regulated and growth condition-independent transcription factor in Saccharomyces cerevisiae.

2014-01-01

[Nucleic Acids Res. 42(17) , e130, (2014)]

Co-ordinated brain and craniofacial development depend upon Patched1/XIAP regulation of cell survival.

2015-02-01

[Hum. Mol. Genet. 24(3) , 698-713, (2015)]

更多文献...