A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance

Joint Authors

Bostick, Tracy
Silva Elipe, Maria Victoria
Ronk, Michael
Tan, Zhixin Jessica

Source

International Journal of Analytical Chemistry

Issue

Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-12, 12 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2008-12-17

Country of Publication

Egypt

No. of Pages

12

Main Subjects

Chemistry
Science

Abstract EN

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

American Psychological Association (APA)

Silva Elipe, Maria Victoria& Tan, Zhixin Jessica& Ronk, Michael& Bostick, Tracy. 2008. A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance. International Journal of Analytical Chemistry،Vol. 2009, no. 2009, pp.1-12.
https://search.emarefa.net/detail/BIM-497279

Modern Language Association (MLA)

Silva Elipe, Maria Victoria…[et al.]. A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance. International Journal of Analytical Chemistry No. 2009 (2009), pp.1-12.
https://search.emarefa.net/detail/BIM-497279

American Medical Association (AMA)

Silva Elipe, Maria Victoria& Tan, Zhixin Jessica& Ronk, Michael& Bostick, Tracy. A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance. International Journal of Analytical Chemistry. 2008. Vol. 2009, no. 2009, pp.1-12.
https://search.emarefa.net/detail/BIM-497279

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-497279