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Healthcare Products, Skin Sensitizer

Cosmetics, Creams, Hair Dyes etc. 


Although para-phenylenediamine (PPD) is known to cause severe allergic contact dermatitis in consequence of autoxidation and/or skin metabolism pathways, it is commonly utilized as an ingredient in permanent hair dyes and dark colored cosmetics. The ROXY EC/LC system as a purely instrumental approach has been used successfully to simultaneously accelerate the autoxidation process and to simulate the metabolic activation of PPD.

Electrochemistry (EC) in combination with electrospray ionization mass spectrometry (ESI-MS) was used to assess the skin-sensitizing potential of PPD. Online and offline coupled EC/ESI-MS experiments were carried out and the emerging oxidation products were investigated. In a second approach, these primary species were allowed to react with the nucleophiles glutathione (GSH), cysteine (Cys), humn serum albumin (HSA) in order to evaluate their reactivity. The reactive p-phenylene quinone diimine (PPQD), which can form upon autoxidation and/or skin metabolism of PPD, was effectively generated in the electrochemical cell. Conjugation with GSH, Cys and HSA was successfully proven. It was found that EC/MS is a well-suited approach for the targeted generation of reactive haptens such as PPQD and the resulting species were further reacted with different proteins leading to diverse hapten-protein complexes.

Thereby, problems related to the complex matrix present in conventional in vitro or in vivo methods could effectively be avoided.

Mass Voltamogram Para-Phenylenediamine (PPD)


(a) PPD, (b) PPD under constant addition of GSH, and (c) PPD under constant addition of Cys. The plots were obtained using either the normal (a) or the extended (b, c) online coupled EC/ESI-MS setup after plotting the continuously recorded mass spectra in dependence on the applied potential in the EC cell. If not marked otherwise, the given m/z data relates to the [M+H]+ ions of the detected species. Molecular structures of oxidation products and adducts are depicted representatively for their corresponding protonated species. The intensity is given in counts per second (cps). Ref: Sandra Jahn et al., Rapid Commun. Mass Spectrom. 2012, 26, 1453–1464



Application Notebook

Posters

  • 221_079_01 - Insights into Nucleic Acids Oxidation by EC─LC─MS
  • 221_090_01 - Degradation of Xenobiotics by OnLine EC─MS (Sulfadiazine)
  • 221_116_01 - Enhanced Pharmaceutical Stability Testing (Naltrexone, Oxycodone)
  • 221_117_01 - Mimicking Drug Metabolism (Verapamil, Amodiaquine)
  • 221_226_02 - The Application of EC─MS to Pharmaceutical Stability Testing and Degradant Synthesis (Ezlopitant)
  • 221_232_01 - Lipid Oxidation (Phospholipids ─ POPE, PLPE, PAPE)
  • 221_240_01 - Metabolism (Overview ROXY EC applications)
  • 221_241_01 - Reduction (Insuline, Avastin Fab)
  • 221_242_01 - Drug Stability Testing (Ezlopitant)
  • 221_244_01 - New EC cell for reduction of protein disulfide bonds in HDX─MS (Insuline, NGF, VEGF)
  • 221_246_01 - Environmental degradation (Triclosan)
  • 221_247_01 - EC Simulation of Phase I Metabolism of Three Novel Cardiovascular Drugs (Rivaroxaban, Aliskiren, Prasugrel)
  • 221_248_02 - EC Reduction of Disulfide Bonds in Proteins & Biopharmaceuticals (Insulin, Avastin Fab, NGF, VEGF)


23286982 - In chemico evaluation of skin metabolism: Investigation of eugenol and isoeugenol by electrochemistry coupled to liquid chromatography and mass spectrometry.
Melles D, Vielhaber T, Baumann A, Zazzeroni R, Karst U.; J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Jan 15;913-914:106-12. doi: 10.1016/j.jchromb.2012.12.004. Epub 2012 Dec 11.

22592989 - Electrochemistry/mass spectrometry as a tool in the investigation of the potent skin sensitizer p-phenylenediamine and its reactivity toward nucleophiles.
Jahn S, Faber H, Zazzeroni R, Karst U.; Rapid Commun Mass Spectrom. 2012 Jun 30;26(12):1453-64. doi: 10.1002/rcm.6249.

22592985 - Electrochemistry/liquid chromatography/mass spectrometry to demonstrate irreversible binding of the skin allergen p-phenylenediamine to proteins.
Jahn S, Faber H, Zazzeroni R, Karst U.; Rapid Commun Mass Spectrom. 2012 Jun 30;26(12):1415-25. doi: 10.1002/rcm.6247.

22227746 - Electrochemical oxidation and protein adduct formation of aniline: a liquid chromatography/mass spectrometry study.
Melles D, Vielhaber T, Baumann A, Zazzeroni R, Karst U.; Anal Bioanal Chem. 2012 Apr;403(2):377-84. doi: 10.1007/s00216-011-5673-0. Epub 2012 Jan 8.

2012-04 - Electrochemistry/liquid chromatography/mass spectrometry to demonstrate irreversible binding of the skin allergen phenylenediamine to proteins
Rapid communications in mass spectrometry, 2012, 26(12), 1415-1425;

2012-06 - Electrochemistry/mass spectrometry as a tool in the investigation of the potent skin sensitizer phenylenediamine and its reactivity toward nucleophiles
S. Jahn, U. Karst et al., Rapid communications in mass spectrometry, 2012, 26(12), 1453-1464;

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