Chemometrically assisted development and validation of LC-MS/MS method for the analysis of potential genotoxic impurities in meropenem active pharmaceutical ingredient
Само за регистроване кориснике
2017
Аутори
Grigori, KaterinaLoukas, Yannis L.
Malenović, Anđelija
Samara, Vicky
Kalaskani, Anastasia
Dimovasili, Efi
Kalovidouri, Magda
Dotsikas, Yannis
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
A sensitive Liquid Chromatography tandem mass spectrometry (LC MS/MS) method was developed and validated for the quantitative analysis of three potential genotoxic impurities (318BP, M9, S5) in meropenem Active Pharmaceutical Ingredient (API). Due to the requirement for LOD values in ppb range, a high concentration of meropenem API (30 ing/mL) had to be injected. Therefore, efficient determination of meropenem from its impurities became a critical aim of this study, in order to divert meropenem to waste, via a switching valve. After the selection of the important factors affecting analytes' elution, a Box-Behnken design was utilized to set the plan of experiments conducted with UV detector. As responses, the separation factors between the last eluting impurity and meropenem, as well as meropenem retention factor k were used. Grid point search methodology was implemented aiming to obtain the optimal conditions that simultaneously comply to the conflicted criteria. Optimal mobile phase c...onsisted of ACN, methanol and 0.09% HCOOH at a ratio 71/3.5/15.5 v/v. All impurities and internal standard omeprazole were eluted before 7.5 min and at 8.0 min the eluents were directed to waste. The protocol was transferred to LC-MS/MS and validated according to ICH guidelines.
Кључне речи:
Meropenem / LC-MS/MS / Genotoxk impurities / Box-Behnken / Grid point search methodologyИзвор:
Journal of Pharmaceutical and Biomedical Analysis, 2017, 145, 307-314Издавач:
- Elsevier Science BV, Amsterdam
DOI: 10.1016/j.jpba.2017.06.061
ISSN: 0731-7085
PubMed: 28709127
WoS: 000410872200038
Scopus: 2-s2.0-85022201663
Институција/група
PharmacyTY - JOUR AU - Grigori, Katerina AU - Loukas, Yannis L. AU - Malenović, Anđelija AU - Samara, Vicky AU - Kalaskani, Anastasia AU - Dimovasili, Efi AU - Kalovidouri, Magda AU - Dotsikas, Yannis PY - 2017 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2832 AB - A sensitive Liquid Chromatography tandem mass spectrometry (LC MS/MS) method was developed and validated for the quantitative analysis of three potential genotoxic impurities (318BP, M9, S5) in meropenem Active Pharmaceutical Ingredient (API). Due to the requirement for LOD values in ppb range, a high concentration of meropenem API (30 ing/mL) had to be injected. Therefore, efficient determination of meropenem from its impurities became a critical aim of this study, in order to divert meropenem to waste, via a switching valve. After the selection of the important factors affecting analytes' elution, a Box-Behnken design was utilized to set the plan of experiments conducted with UV detector. As responses, the separation factors between the last eluting impurity and meropenem, as well as meropenem retention factor k were used. Grid point search methodology was implemented aiming to obtain the optimal conditions that simultaneously comply to the conflicted criteria. Optimal mobile phase consisted of ACN, methanol and 0.09% HCOOH at a ratio 71/3.5/15.5 v/v. All impurities and internal standard omeprazole were eluted before 7.5 min and at 8.0 min the eluents were directed to waste. The protocol was transferred to LC-MS/MS and validated according to ICH guidelines. PB - Elsevier Science BV, Amsterdam T2 - Journal of Pharmaceutical and Biomedical Analysis T1 - Chemometrically assisted development and validation of LC-MS/MS method for the analysis of potential genotoxic impurities in meropenem active pharmaceutical ingredient VL - 145 SP - 307 EP - 314 DO - 10.1016/j.jpba.2017.06.061 ER -
@article{ author = "Grigori, Katerina and Loukas, Yannis L. and Malenović, Anđelija and Samara, Vicky and Kalaskani, Anastasia and Dimovasili, Efi and Kalovidouri, Magda and Dotsikas, Yannis", year = "2017", abstract = "A sensitive Liquid Chromatography tandem mass spectrometry (LC MS/MS) method was developed and validated for the quantitative analysis of three potential genotoxic impurities (318BP, M9, S5) in meropenem Active Pharmaceutical Ingredient (API). Due to the requirement for LOD values in ppb range, a high concentration of meropenem API (30 ing/mL) had to be injected. Therefore, efficient determination of meropenem from its impurities became a critical aim of this study, in order to divert meropenem to waste, via a switching valve. After the selection of the important factors affecting analytes' elution, a Box-Behnken design was utilized to set the plan of experiments conducted with UV detector. As responses, the separation factors between the last eluting impurity and meropenem, as well as meropenem retention factor k were used. Grid point search methodology was implemented aiming to obtain the optimal conditions that simultaneously comply to the conflicted criteria. Optimal mobile phase consisted of ACN, methanol and 0.09% HCOOH at a ratio 71/3.5/15.5 v/v. All impurities and internal standard omeprazole were eluted before 7.5 min and at 8.0 min the eluents were directed to waste. The protocol was transferred to LC-MS/MS and validated according to ICH guidelines.", publisher = "Elsevier Science BV, Amsterdam", journal = "Journal of Pharmaceutical and Biomedical Analysis", title = "Chemometrically assisted development and validation of LC-MS/MS method for the analysis of potential genotoxic impurities in meropenem active pharmaceutical ingredient", volume = "145", pages = "307-314", doi = "10.1016/j.jpba.2017.06.061" }
Grigori, K., Loukas, Y. L., Malenović, A., Samara, V., Kalaskani, A., Dimovasili, E., Kalovidouri, M.,& Dotsikas, Y.. (2017). Chemometrically assisted development and validation of LC-MS/MS method for the analysis of potential genotoxic impurities in meropenem active pharmaceutical ingredient. in Journal of Pharmaceutical and Biomedical Analysis Elsevier Science BV, Amsterdam., 145, 307-314. https://doi.org/10.1016/j.jpba.2017.06.061
Grigori K, Loukas YL, Malenović A, Samara V, Kalaskani A, Dimovasili E, Kalovidouri M, Dotsikas Y. Chemometrically assisted development and validation of LC-MS/MS method for the analysis of potential genotoxic impurities in meropenem active pharmaceutical ingredient. in Journal of Pharmaceutical and Biomedical Analysis. 2017;145:307-314. doi:10.1016/j.jpba.2017.06.061 .
Grigori, Katerina, Loukas, Yannis L., Malenović, Anđelija, Samara, Vicky, Kalaskani, Anastasia, Dimovasili, Efi, Kalovidouri, Magda, Dotsikas, Yannis, "Chemometrically assisted development and validation of LC-MS/MS method for the analysis of potential genotoxic impurities in meropenem active pharmaceutical ingredient" in Journal of Pharmaceutical and Biomedical Analysis, 145 (2017):307-314, https://doi.org/10.1016/j.jpba.2017.06.061 . .