title: A generic approach to the impurity profiling of drugs using standardised and independent capillary zone electrophoresis methods coupled to electrospray ionisation mass spectrometry.
abstract: 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 background electrolyte conditions were found to be: 60/40 v/v 10 mM ammonium formate pH 3.5/organic, 60/40 v/v 10 mM ammonium acetate pH 7.0/organic and 10 mM 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 mM 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.
authors.affiliation: Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Vassort
authors.forename: David A
authors.initials: DA
authors.lastname: Barrett
authors.forename: P Nicholas
authors.initials: PN
authors.lastname: Shaw
authors.forename: Paul D
authors.initials: PD
authors.lastname: Ferguson
authors.forename: Roman
authors.initials: R
authors.lastname: Szucs
mesh_terms: D004340:Drug Contamination; D019075:Electrophoresis, Capillary / Q000379:methods* / Q000592:standards; D004364:Pharmaceutical Preparations / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards
chemical_list: D004364:Pharmaceutical Preparations