TY  - 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 . .