TITLE:
Quantitation of Genetox Impurities Using a Surrogate Standard Approach
AUTHORS:
Heather Wang, Regina Nardi, Yuri Bereznitski, Roy Helmy, David J. Waterhouse
KEYWORDS:
Potential Genotoxic Impurity (PGI); Active Pharmaceutical Ingredient (API); Mass Spectrometry;Surrogate Standard; Analyte; Relative Response Factor (RRF)
JOURNAL NAME:
Journal of Analytical Sciences, Methods and Instrumentation,
Vol.3 No.3,
September
25,
2013
ABSTRACT: With the ever increasing complexity of
active pharmaceutical ingredient (API) preparations, more potential genotoxic
impurities (PGI’s) are being observed. It is thus necessary to determine if
these PGI’s are present in the final API’s, and if they are present, to ensure
the levels are acceptable for any clinical uses. For PGI’s that have authentic
standards available, quantitation can be accomplished in a straightforward
manner. However, for PGI’s that are expected to form through rearrangements or
side reactions, authentic standards may not be readily available, significantly
complicating the analysis. In this study we describe a surrogate standard
approach for quantifying PGI’s that allows for relative response factor
calculations of PGI species utilizing both gas chromatography-mass spectrometry
(GC-MS) and liquid chromatography-mass spectrometry (LC-MS).