Linked Life Data

20140079

Source:http://linkedlifedata.com/resource/pubmed/id/20140079

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-2-8
pubmed:abstractText
In the initial scale-up batches of the experimental drug substance AMG 517, a pair of unexpected impurities was observed by HPLC. Analysis of data from initial LC-MS experiments indicated the presence of two dimer-like molecules. One impurity had an additional sulfur atom incorporated into its structure relative to the other impurity. Isolation of the impurities was performed, and further structural elucidation experiments were conducted with high-resolution LC-MS and 2D NMR. The dimeric structures were confirmed, with one of the impurities having an unexpected C-S-C linkage. Based on the synthetic route of AMG 517, it was unlikely that these impurities were generated during the last two steps of the process. Stress studies on the enriched impurities were carried out to further confirm the existence of the C-S-C linkage in the benzothiazole portion of AMG 517. Further investigation revealed that these two dimeric impurities originated from existing impurities in the AMG 517 starting material, N-acetyl benzothiazole. The characterization of these two dimeric impurities allowed for better quality control of new batches of the N-acetyl benzothiazole starting material. As a result, subsequent batches of AMG 517 contained no reportable levels of these two impurities.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:status
PubMed-not-MEDLINE
pubmed:issn
1687-8779
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
2009
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
768743
pubmed:year
2009
pubmed:articleTitle
A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance.
pubmed:affiliation
Department of Analytical Research and Development, Amgen Inc., Thousand Oaks, CA 91320, USA.
pubmed:publicationType
Journal Article