The separation and characterization of the unknown degradation product of second-generation antipsychotic drug ziprasidone are essential for defining the genotoxic potential of the compound. The aim of this study was to develop a simple UHPLC method coupled with tandem mass spectrometry (MS/MS) for chemical characterization of an unknown degradant, and the separation and quantification of ziprasidone and its five main impurities (I-V) in the raw material and pharmaceuticals. Chromatographic conditions were optimized by experimental design. The MS/MS fragmentation conditions were optimized individually for each compound in order to obtain both specific fragments and high signal intensity. A rapid and sensitive UHPLC-MS/MS method was developed. All seven analytes were eluted within the 7 min run time. The best separation was obtained on the Acquity UPLC BEH C-18 (50 x 2.1 mm x 1.7 mu m) column in gradient mode with ammonium-formate buffer (10 mm; pH 4.7) and acetonitrile as mobile phase,... with the flow rate of 0.3 mL min(-1) and at the column temperature of 30 degrees C. The new UHPLC-MS/MS method was fully validated and all validation parameters were confirmed. The fragmentation pathways and chemical characterization of an unknown degradant were proposed and it was confirmed that there are no structural alerts concerning genotoxicity.
Keywords:
chromatographic functions / degradation products / experimental design / tandem mass spectrometry / ziprasidone
TY - JOUR
AU - Čarapić, Marija
AU - Nikolić, Katarina
AU - Marković, Bojan
AU - Petković, Miloš
AU - Pavlović, Milena
AU - Agbaba, Danica
PY - 2019
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3329
AB - The separation and characterization of the unknown degradation product of second-generation antipsychotic drug ziprasidone are essential for defining the genotoxic potential of the compound. The aim of this study was to develop a simple UHPLC method coupled with tandem mass spectrometry (MS/MS) for chemical characterization of an unknown degradant, and the separation and quantification of ziprasidone and its five main impurities (I-V) in the raw material and pharmaceuticals. Chromatographic conditions were optimized by experimental design. The MS/MS fragmentation conditions were optimized individually for each compound in order to obtain both specific fragments and high signal intensity. A rapid and sensitive UHPLC-MS/MS method was developed. All seven analytes were eluted within the 7 min run time. The best separation was obtained on the Acquity UPLC BEH C-18 (50 x 2.1 mm x 1.7 mu m) column in gradient mode with ammonium-formate buffer (10 mm; pH 4.7) and acetonitrile as mobile phase, with the flow rate of 0.3 mL min(-1) and at the column temperature of 30 degrees C. The new UHPLC-MS/MS method was fully validated and all validation parameters were confirmed. The fragmentation pathways and chemical characterization of an unknown degradant were proposed and it was confirmed that there are no structural alerts concerning genotoxicity.
PB - Wiley, Hoboken
T2 - Biomedical Chromatography
T1 - Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities
VL - 33
IS - 2
DO - 10.1002/bmc.4384
ER -
@article{
author = "Čarapić, Marija and Nikolić, Katarina and Marković, Bojan and Petković, Miloš and Pavlović, Milena and Agbaba, Danica",
year = "2019",
abstract = "The separation and characterization of the unknown degradation product of second-generation antipsychotic drug ziprasidone are essential for defining the genotoxic potential of the compound. The aim of this study was to develop a simple UHPLC method coupled with tandem mass spectrometry (MS/MS) for chemical characterization of an unknown degradant, and the separation and quantification of ziprasidone and its five main impurities (I-V) in the raw material and pharmaceuticals. Chromatographic conditions were optimized by experimental design. The MS/MS fragmentation conditions were optimized individually for each compound in order to obtain both specific fragments and high signal intensity. A rapid and sensitive UHPLC-MS/MS method was developed. All seven analytes were eluted within the 7 min run time. The best separation was obtained on the Acquity UPLC BEH C-18 (50 x 2.1 mm x 1.7 mu m) column in gradient mode with ammonium-formate buffer (10 mm; pH 4.7) and acetonitrile as mobile phase, with the flow rate of 0.3 mL min(-1) and at the column temperature of 30 degrees C. The new UHPLC-MS/MS method was fully validated and all validation parameters were confirmed. The fragmentation pathways and chemical characterization of an unknown degradant were proposed and it was confirmed that there are no structural alerts concerning genotoxicity.",
publisher = "Wiley, Hoboken",
journal = "Biomedical Chromatography",
title = "Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities",
volume = "33",
number = "2",
doi = "10.1002/bmc.4384"
}
Čarapić, M., Nikolić, K., Marković, B., Petković, M., Pavlović, M.,& Agbaba, D.. (2019). Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities. in Biomedical Chromatography
Wiley, Hoboken., 33(2).
https://doi.org/10.1002/bmc.4384
Čarapić M, Nikolić K, Marković B, Petković M, Pavlović M, Agbaba D. Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities. in Biomedical Chromatography. 2019;33(2).
doi:10.1002/bmc.4384 .
Čarapić, Marija, Nikolić, Katarina, Marković, Bojan, Petković, Miloš, Pavlović, Milena, Agbaba, Danica, "Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities" in Biomedical Chromatography, 33, no. 2 (2019),
https://doi.org/10.1002/bmc.4384 . .
