Lausević, Mila

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  • Lausević, Mila (3)
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Author's Bibliography

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

Protić, Ana; Radisić, Marina; Golubović, Jelena; Otašević, Biljana; Zečević, Mira; Lausević, Mila

(Springer Heidelberg, Heidelberg, 2016)

TY  - 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 . .
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Forced degradation study of torasemide: Characterization of its degradation products

Jović, Žarko; Živanović, Ljiljana; Protić, Ana; Radisić, Marina; Lausević, Mila; Malešević, Marija; Zečević, Mira

(Taylor & Francis Inc, Philadelphia, 2013)

TY  - JOUR
AU  - Jović, Žarko
AU  - Živanović, Ljiljana
AU  - Protić, Ana
AU  - Radisić, Marina
AU  - Lausević, Mila
AU  - Malešević, Marija
AU  - Zečević, Mira
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1961
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3431
AB  - Torasemide was subjected to forced degradation studies. Stress conditions were varied concerning hydrolysis (acid, base, and neutral), oxidation, photolysis, and thermal degradation in order to identify the potential degradation products and consequently establish the possible degradation pathways and intrinsic stability of the drug. The study was performed according to ICH guidelines and drug was found to be relatively stable in the solid form. It showed that torasemide degraded significantly under acidic, neutral and alkaline conditions and resulted in formation of degradation product R2. When temperature was increased the degradation was accelerated. Also, the drug showed slight instability under extreme oxidative stress conditions which resulted in formation of two degradation products in total. The drug and degradation products have been separated employing gradient elution method on Zorbax SB C-18 analytical column. To characterize the degradation products LC-MSn was applied. The mass fragmentation pattern was established using single quadrupole and ion trap mass analyzers. Finally, the most possible degradation mechanism of torasemide in different experimental conditions was proposed.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Forced degradation study of torasemide: Characterization of its degradation products
VL  - 36
IS  - 15
SP  - 2082
EP  - 2094
DO  - 10.1080/10826076.2012.712932
ER  - 
@article{
author = "Jović, Žarko and Živanović, Ljiljana and Protić, Ana and Radisić, Marina and Lausević, Mila and Malešević, Marija and Zečević, Mira",
year = "2013",
abstract = "Torasemide was subjected to forced degradation studies. Stress conditions were varied concerning hydrolysis (acid, base, and neutral), oxidation, photolysis, and thermal degradation in order to identify the potential degradation products and consequently establish the possible degradation pathways and intrinsic stability of the drug. The study was performed according to ICH guidelines and drug was found to be relatively stable in the solid form. It showed that torasemide degraded significantly under acidic, neutral and alkaline conditions and resulted in formation of degradation product R2. When temperature was increased the degradation was accelerated. Also, the drug showed slight instability under extreme oxidative stress conditions which resulted in formation of two degradation products in total. The drug and degradation products have been separated employing gradient elution method on Zorbax SB C-18 analytical column. To characterize the degradation products LC-MSn was applied. The mass fragmentation pattern was established using single quadrupole and ion trap mass analyzers. Finally, the most possible degradation mechanism of torasemide in different experimental conditions was proposed.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Forced degradation study of torasemide: Characterization of its degradation products",
volume = "36",
number = "15",
pages = "2082-2094",
doi = "10.1080/10826076.2012.712932"
}
Jović, Ž., Živanović, L., Protić, A., Radisić, M., Lausević, M., Malešević, M.,& Zečević, M.. (2013). Forced degradation study of torasemide: Characterization of its degradation products. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc, Philadelphia., 36(15), 2082-2094.
https://doi.org/10.1080/10826076.2012.712932
Jović Ž, Živanović L, Protić A, Radisić M, Lausević M, Malešević M, Zečević M. Forced degradation study of torasemide: Characterization of its degradation products. in Journal of Liquid Chromatography & Related Technologies. 2013;36(15):2082-2094.
doi:10.1080/10826076.2012.712932 .
Jović, Žarko, Živanović, Ljiljana, Protić, Ana, Radisić, Marina, Lausević, Mila, Malešević, Marija, Zečević, Mira, "Forced degradation study of torasemide: Characterization of its degradation products" in Journal of Liquid Chromatography & Related Technologies, 36, no. 15 (2013):2082-2094,
https://doi.org/10.1080/10826076.2012.712932 . .
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Forced degradation study of torasemide: Characterization of its degradation products

Jović, Žarko; Živanović, Ljiljana; Protić, Ana; Radisić, Marina; Lausević, Mila; Malešević, Marija; Zečević, Mira

(Taylor & Francis Inc, Philadelphia, 2013)

TY  - JOUR
AU  - Jović, Žarko
AU  - Živanović, Ljiljana
AU  - Protić, Ana
AU  - Radisić, Marina
AU  - Lausević, Mila
AU  - Malešević, Marija
AU  - Zečević, Mira
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1961
AB  - Torasemide was subjected to forced degradation studies. Stress conditions were varied concerning hydrolysis (acid, base, and neutral), oxidation, photolysis, and thermal degradation in order to identify the potential degradation products and consequently establish the possible degradation pathways and intrinsic stability of the drug. The study was performed according to ICH guidelines and drug was found to be relatively stable in the solid form. It showed that torasemide degraded significantly under acidic, neutral and alkaline conditions and resulted in formation of degradation product R2. When temperature was increased the degradation was accelerated. Also, the drug showed slight instability under extreme oxidative stress conditions which resulted in formation of two degradation products in total. The drug and degradation products have been separated employing gradient elution method on Zorbax SB C-18 analytical column. To characterize the degradation products LC-MSn was applied. The mass fragmentation pattern was established using single quadrupole and ion trap mass analyzers. Finally, the most possible degradation mechanism of torasemide in different experimental conditions was proposed.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Forced degradation study of torasemide: Characterization of its degradation products
VL  - 36
IS  - 15
SP  - 2082
EP  - 2094
DO  - 10.1080/10826076.2012.712932
ER  - 
@article{
author = "Jović, Žarko and Živanović, Ljiljana and Protić, Ana and Radisić, Marina and Lausević, Mila and Malešević, Marija and Zečević, Mira",
year = "2013",
abstract = "Torasemide was subjected to forced degradation studies. Stress conditions were varied concerning hydrolysis (acid, base, and neutral), oxidation, photolysis, and thermal degradation in order to identify the potential degradation products and consequently establish the possible degradation pathways and intrinsic stability of the drug. The study was performed according to ICH guidelines and drug was found to be relatively stable in the solid form. It showed that torasemide degraded significantly under acidic, neutral and alkaline conditions and resulted in formation of degradation product R2. When temperature was increased the degradation was accelerated. Also, the drug showed slight instability under extreme oxidative stress conditions which resulted in formation of two degradation products in total. The drug and degradation products have been separated employing gradient elution method on Zorbax SB C-18 analytical column. To characterize the degradation products LC-MSn was applied. The mass fragmentation pattern was established using single quadrupole and ion trap mass analyzers. Finally, the most possible degradation mechanism of torasemide in different experimental conditions was proposed.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Forced degradation study of torasemide: Characterization of its degradation products",
volume = "36",
number = "15",
pages = "2082-2094",
doi = "10.1080/10826076.2012.712932"
}
Jović, Ž., Živanović, L., Protić, A., Radisić, M., Lausević, M., Malešević, M.,& Zečević, M.. (2013). Forced degradation study of torasemide: Characterization of its degradation products. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc, Philadelphia., 36(15), 2082-2094.
https://doi.org/10.1080/10826076.2012.712932
Jović Ž, Živanović L, Protić A, Radisić M, Lausević M, Malešević M, Zečević M. Forced degradation study of torasemide: Characterization of its degradation products. in Journal of Liquid Chromatography & Related Technologies. 2013;36(15):2082-2094.
doi:10.1080/10826076.2012.712932 .
Jović, Žarko, Živanović, Ljiljana, Protić, Ana, Radisić, Marina, Lausević, Mila, Malešević, Marija, Zečević, Mira, "Forced degradation study of torasemide: Characterization of its degradation products" in Journal of Liquid Chromatography & Related Technologies, 36, no. 15 (2013):2082-2094,
https://doi.org/10.1080/10826076.2012.712932 . .
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