Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn
Authorized Users Only
2016
Authors
Protić, Ana
Radisić, Marina
Golubović, Jelena

Otašević, Biljana

Zečević, Mira

Lausević, Mila
Article (Published version)

Metadata
Show full item recordAbstract
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 A mu m). The mobile phase consisted of 26 % acetonitrile and 74 % 9 mM ammonium acetate pH 5.87, the column temperature was set at 40 A degrees C, and the flow rate of the mobile phase was 400 A mu L 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 o...f 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.
Source:
Chromatographia, 2016, 79, 13-14, 919-926Publisher:
- Springer Heidelberg, Heidelberg
Funding / projects:
DOI: 10.1007/s10337-016-3092-2
ISSN: 0009-5893
WoS: 000379157500012
Scopus: 2-s2.0-84969793669
Collections
Institution/Community
PharmacyTY - JOUR AU - Protić, Ana AU - Radisić, Marina AU - Golubović, Jelena AU - Otašević, Biljana AU - Zečević, Mira AU - Lausević, Mila PY - 2016 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2746 AB - 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 A mu m). The mobile phase consisted of 26 % acetonitrile and 74 % 9 mM ammonium acetate pH 5.87, the column temperature was set at 40 A degrees C, and the flow rate of the mobile phase was 400 A mu L 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. PB - Springer Heidelberg, Heidelberg T2 - Chromatographia T1 - Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn VL - 79 IS - 13-14 SP - 919 EP - 926 DO - 10.1007/s10337-016-3092-2 ER -
@article{ author = "Protić, Ana and Radisić, Marina and Golubović, Jelena and Otašević, Biljana and Zečević, Mira and Lausević, Mila", year = "2016", 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 A mu m). The mobile phase consisted of 26 % acetonitrile and 74 % 9 mM ammonium acetate pH 5.87, the column temperature was set at 40 A degrees C, and the flow rate of the mobile phase was 400 A mu L 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.", publisher = "Springer Heidelberg, Heidelberg", journal = "Chromatographia", title = "Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn", volume = "79", number = "13-14", pages = "919-926", doi = "10.1007/s10337-016-3092-2" }
Protić, A., Radisić, M., Golubović, J., Otašević, B., Zečević, M.,& Lausević, M.. (2016). Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn. in Chromatographia Springer Heidelberg, Heidelberg., 79(13-14), 919-926. https://doi.org/10.1007/s10337-016-3092-2
Protić A, Radisić M, Golubović J, Otašević B, Zečević M, Lausević M. Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn. in Chromatographia. 2016;79(13-14):919-926. doi:10.1007/s10337-016-3092-2 .
Protić, Ana, Radisić, Marina, Golubović, Jelena, Otašević, Biljana, Zečević, Mira, Lausević, Mila, "Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn" in Chromatographia, 79, no. 13-14 (2016):919-926, https://doi.org/10.1007/s10337-016-3092-2 . .