Published:Journal of Chromatographic Science,
ISSN 0021-9665 Volume
47, Number 4, April 2009, pp. 315-319
Low Level Determination of 4-Amino-2-Ethoxy-Cinnamic
Acid and its Ethyl Ester in a Drug Substance and its Formulation
Prototypes by HPLC–UV-DAD
A. Soman, S. Jacob, and F. Swanek
Analytical Sciences Department, Research and Development Center,
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT
06877
A reversed-phase high-performance liquid chromatographic
method (HPLC) with diode-array detection (DAD) has been evaluated
for monitoring trace levels of impurities, such as 4-amino-2-ethoxy-cinnamic
acid (impurity A), hydrochloride salt of 4-amino-2-ethoxy-ethyl
cinnamate (impurity B), and 4-bromo-3-ethoxy-nitrobenzene (impurity
C), in drug substance and 3 different formulation prototypes.
These compounds have been highlighted as potential genotoxins
and 2-ethoxy-4-amino-cinnamic acid (impurity A) as possible degradant
isolated during the synthesis of BI drug substance. HPLC–UV-DAD
was found to be more promising, and limits of quantification
were between 0.09 and 0.6 µg/mL, which enabled detection
limits in drug substance at 2–15 ppm for a 15 mg/mL solution.
All three genotoxic impurities are completely resolved from each
other as well as from diluent peaks, drug substance, and other
related impurities within 40 min. The retention times of impurities
A, B, and C were 3.4, 13.1, and 21.3 min. The results demonstrating
the specificity, assay precision, recovery, linearity, and range
achieved during the method validation experiments are presented
in this paper.
Reproduction
of editorial content of this journal is prohibited without publisher’s
permission.
This
article is available in its entirety by fax for $40.00.
Visa, MasterCard & Amex accepted.
To
order electronicallyclick here or call: 847-647-2900 ext. 1323 or fax request to: 847-647-1155.
Please
indicate JCS volume and issue along with
page numbers.
For permission to reuse material from Journal of Chromatographic Science, please access www.copyright.com or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of uses.
