title: Multidimensional isotope analysis of carbon, hydrogen and oxygen as tool for identification of the origin of ibuprofen.
abstract: Multidimensional isotope profiling is a useful tool for the characterization of the provenance of active pharmaceutical ingredients (API). To evaluate this approach, samples of the nonsteroidal anti-inflammatory drug (NSAIDs) ibuprofen were collected from 32 manufactures and 13 countries, and carbon, hydrogen and oxygen isotope ratios were analyzed by elemental analyzer, chromium-filled elemental analyzer and high temperature conversion elemental analyzer (EA, Cr-EA and TC/EA) coupled to an isotope ratio mass spectrometry (IRMS). The range of isotope values of ibuprofen (δ(13)C: -33.2±0.1‰ to -27.4±0.1‰; δ(2)H: -121.4±1.5‰ to -41.2±0.8‰; and δ(18)O: -12.6±0.3‰ to 19.0±0.6‰) allowed characterization and distinction of 5 groups, which reflect synthetic pathways and/or use of different raw materials, as well as possible isotope fractionation during the synthesis reactions. This study highlights that multi isotope fingerprinting has potential for identification of sources, and provides a database of isotope composition of ibuprofen (δ(2)H, δ(13)C, δ(18)O) that might improve the tracing of origin, transport pathways and environmental fate of ibuprofen.
authors.affiliation: Helmholtz-Centre for Environmental Research - UFZ, Department for Isotope Biogeochemistry, Permoserstrasse 15, 04318 Leipzig, Germany.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Gilevska
authors.affiliation: Helmholtz-Centre for Environmental Research - UFZ, Department for Isotope Biogeochemistry, Permoserstrasse 15, 04318 Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gehre
authors.affiliation: Helmholtz-Centre for Environmental Research - UFZ, Department for Isotope Biogeochemistry, Permoserstrasse 15, 04318 Leipzig, Germany. Electronic address: hans.richnow@ufz.de.
authors.forename: Hans Hermann
authors.initials: HH
authors.lastname: Richnow
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis* / Q000138:chemical synthesis; D002247:Carbon Isotopes / Q000032:analysis*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D058110:Counterfeit Drugs / Q000032:analysis* / Q000138:chemical synthesis; D006859:Hydrogen / Q000032:analysis*; D007052:Ibuprofen / Q000032:analysis* / Q000138:chemical synthesis; D013058:Mass Spectrometry / Q000379:methods*; D010103:Oxygen Isotopes / Q000032:analysis*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002247:Carbon Isotopes; D058110:Counterfeit Drugs; D010103:Oxygen Isotopes; D006859:Hydrogen; D007052:Ibuprofen
keywords: Drug counterfeiting; IRMS; Ibuprofen; Isotope ratios; Synthetic pathway; δ(13)C; δ(18)O; δ(2)H