title: Applicability of total reflection X-ray fluorescence (TXRF) as a screening platform for pharmaceutical inorganic impurity analysis.
abstract: Palladium (Pd) is extensively used in pharmaceutical small molecule drug substance processes, however it must be removed prior to release of the active pharmaceutical ingredient (API). Evaluation of four TXRF instruments and configurations were compared to ICP-MS instrumentation for trace metal analysis, most importantly for Pd. Standards and six pharmaceutical drug substances, triprolidine HCl, diphenhydramine HCl, chlorpheniramine maleate, pseudoephedrine HCl, ephedrine sulfate, and scopolamine HBr, were analyzed to determine linearity, sensitivity, accuracy, and precision for Pd plus Cr, Fe, Cu, Rh, and Pt versus interferences, particularly from Cl, S, and Ar, on the various X-ray fluorescence lines. Irrespective of instrument platform, in general X-ray sources capable of accessing Pd-K lines were found to be most effective in determination of Pd in APIs.
authors.affiliation: Analytical Research and Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. bshaw@amgen.com
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Shaw
authors.forename: David J
authors.initials: DJ
authors.lastname: Semin
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rider
authors.forename: Meredith R
authors.initials: MR
authors.lastname: Beebe
mesh_terms: D002138:Calibration; D002384:Catalysis; D002626:Chemistry, Pharmaceutical; D002744:Chlorpheniramine / Q000737:chemistry; D004155:Diphenhydramine / Q000737:chemistry; D004340:Drug Contamination; D004809:Ephedrine / Q000737:chemistry; D010165:Palladium / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D054199:Pseudoephedrine / Q000737:chemistry; D012601:Scopolamine / Q000737:chemistry; D013052:Spectrometry, X-Ray Emission / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D014311:Triprolidine / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D014311:Triprolidine; D002744:Chlorpheniramine; D010165:Palladium; D054199:Pseudoephedrine; D004155:Diphenhydramine; D012601:Scopolamine; D004809:Ephedrine