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A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry
Author(s) -
Vassort Aurélie,
Barrett David A.,
Shaw P. Nicholas,
Ferguson Paul D.,
Szucs Roman
Publication year - 2005
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200410261
Subject(s) - capillary electrophoresis , capillary electrophoresis–mass spectrometry , mass spectrometry , chromatography , electrospray , electrospray ionization , chemistry , impurity , electrospray mass spectrometry , profiling (computer programming) , analytical chemistry (journal) , computer science , organic chemistry , operating system
Three standardised, capillary zone electrophoresis‐electrospray ionisation mass spectrometry (CZE‐ESI‐MS) methods were developed for the analysis of six drug candidates and their respective process‐related impurities comprising a total of 22 analytes with a range of functional groups and lipophilicities. The selected backround electrolyte conditions were found to be: 60/40 v/v 10 m M ammonium formate pH 3.5/organic, 60/40 v/v 10 m M ammonium acetate pH 7.0/organic and 10 m M piperidine, pH 10.5, where the organic solvent is 50/50 v/v methanol/acetonitrile. The coaxial sheath flow consisted of either 0.1% v/v formic acid in 50/50 v/v methanol/water, or 10 m M ammonium acetate in 50/50 v/v methanol/water, depending on the mixture being analysed. Factor analysis and informational theory were used to quantify the orthogonality of the methods and predict their complementarities. The three selected CZE‐ESI‐MS methods allowed the identification of 21 out of 22 of all the drug candidates and their process‐related impurities and provided orthogonality with four established high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS) methods. These methodologies therefore form the basis of a generic approach to impurity profiling of pharmaceutical drug candidates and can be applied with little or no analytical method development, thereby offering significant resource and time savings.