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Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn

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Abstract

Unknown degradation products of mycophenolate mofetil formed under oxidative stress conditions have been characterized via LC-MSn, using an RP-LC column (50 mm length, 2.1 mm i.d., 1.9 µm). The mobile phase consisted of 26 % acetonitrile and 74 % 9 mM ammonium acetate pH 5.87, the column temperature was set at 40 °C, and the flow rate of the mobile phase was 400 µL min−1. Four degradation products formed under the influence of 15 % hydrogen peroxide after an hour. Two of the degradation products had previously been identified as mycophenolic acid (m/z 321) and the N-oxide of mycophenolate mofetil (m/z 450). The other two unknown degradation products, denoted DP I (m/z 319) and DP II (m/z 466), were investigated in depth in order to identify their structures. The fragmentation patterns of DP I and DP II were established, analyzed, and compared to the fragmentation patterns of mycophenolate mofetil and the N-oxide of mycophenolate mofetil, which aided the elucidation of the structures of the unknown degradation products. The unknown degradation product DP I (m/z 319.2) was proposed to be an oxidized unsaturated mycophenolate aldehyde which also appeared as an ammonium adduct ion at m/z 336.3. The second unknown degradation product, DP II (m/z 466.3), was characterized as a doubly oxidized derivative of mycophenolate mofetil. A possible degradation pathway of mycophenolate mofetil under the influence of an oxidizing agent was also proposed.

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Acknowledgments

These results are part of project no. 172033 financed by the Ministry of Education, Science and Technological Development of the Republic of Serbia.

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Authors and Affiliations

  1. Department of Drug Analysis, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, Serbia

    Ana Protić, Jelena Golubović, Biljana Otašević & Mira Zečević

  2. Department of Analytical Chemistry, Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, Belgrade, Serbia

    Marina Radišić & Mila Laušević

Authors
  1. Ana Protić
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  2. Marina Radišić
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  3. Jelena Golubović
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  4. Biljana Otašević
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  5. Mira Zečević
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  6. Mila Laušević
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Correspondence to Ana Protić.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Protić, A., Radišić, M., Golubović, J. et al. Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn . Chromatographia 79, 919–926 (2016). https://doi.org/10.1007/s10337-016-3092-2

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  • DOI: https://doi.org/10.1007/s10337-016-3092-2

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