title: Validation and application of an HPLC-CAD-TOF/MS method for identification and quantification of pharmaceutical counterions.
abstract: A generic approach for the analysis of counterions of pharmaceutical reference substances, which are established by the laboratory department of the European Pharmacopoeia (Ph. Eur.), was developed. A mixed-mode chromatography method using charged aerosol detection (CAD) published by Zhang et al. separating 25 commonly used pharmaceutical counterions was selected for this purpose. The method was validated in terms of specificity, repeatability, limits of quantification (LOQs), linearity and range according to ICH guideline Q2(R1) and the Technical Guide for the Elaboration of Monographs of the Ph. Eur. Moreover, the applicability of the method for the purpose of counterion identification and quantification in drug substances as well as for the control of inorganic ions as impurities was demonstrated using selected examples of Ph. Eur. reference standards and other samples of substances for pharmaceutical use (e.g. cloxacillin sodium, somatostatin). It was shown that for identification purposes of the parent substance as well as organic ions the chromatographic system can easily be coupled to a mass selective detector without any modification.
authors: Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany.
authors: D
authors: D
authors: Ilko
authors: European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe, Strasbourg, France.
authors: C J
authors: CJ
authors: Nap
authors: Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany.
authors: U
authors: U
authors: Holzgrabe
authors: European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe, Strasbourg, France, stefan.almeling@edqm.eu.
authors: S
authors: S
authors: Almeling
mesh_terms: D000336:Aerosols / Q000032:analysis / Q000592:standards*; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D004340:Drug Contamination; D007477:Ions / Q000032:analysis / Q000592:standards*; D057230:Limit of Detection; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000592:standards; D012015:Reference Standards; D012680:Sensitivity and Specificity
chemical_list: D000336:Aerosols; D007477:Ions; D004364:Pharmaceutical Preparations
keywords: charged aerosol detection (CAD); counterions; mixed-mode chromatography; pharmaceutical analysis; time-of-flight mass spectrometry (TOF/MS)