TY  - JOUR
AU  - Iliou, Katerina
AU  - Malenović, Anđelija
AU  - Loukas, Yannis L.
AU  - Dotsikas, Yannis
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3190
AB  - A novel Liquid Chromatography-tandem mass spectrometry (LC-MS/MS) method is presented for the quantitative determination of two potential genotoxic impurities (PGIs) in rabeprazole active pharmaceutical ingredient (API). In order to overcome the analytical challenges in the trace analysis of PGIs, a development procedure supported by Quality-by-Design (Q1313) principles was evaluated. The efficient separation between rabeprazole and the two PGIs in the shortest analysis time was set as the defined analytical target profile (ATP) and to this purpose utilization of a switching valve allowed the flow to be sent to waste when rabeprazole was eluted. The selected critical quality attributes (CQAs) were the separation criterion s between the critical peak pair and the capacity factor k of the last eluted compound. The effect of the following critical process parameters (CPPs) on the CQAs was studied: %ACN content, the pH and the concentration of the buffer salt in the mobile phase, as well as the stationary phase of the analytical column. D-Optimal design was implemented to set the plan of experiments with UV detector. In order to define the design space, Monte Carlo simulations with 5000 iterations were performed. Acceptance criteria were met for Cs column (50 x 4 mm, 5 p.m), and the region having probability pi >= 95% to achieve satisfactory values of all defined CQAs was computed. The working point was selected with the mobile phase consisting of ACN, ammonium formate 11 mM at a ratio 31/69 v/v with pH-6,8 for the water phase. The LC 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  - Analysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method development
VL  - 149
SP  - 410
EP  - 418
DO  - 10.1016/j.jpba.2017.11.037
ER  - 

@article{
author = "Iliou, Katerina and Malenović, Anđelija and Loukas, Yannis L. and Dotsikas, Yannis",
year = "2018",
abstract = "A novel Liquid Chromatography-tandem mass spectrometry (LC-MS/MS) method is presented for the quantitative determination of two potential genotoxic impurities (PGIs) in rabeprazole active pharmaceutical ingredient (API). In order to overcome the analytical challenges in the trace analysis of PGIs, a development procedure supported by Quality-by-Design (Q1313) principles was evaluated. The efficient separation between rabeprazole and the two PGIs in the shortest analysis time was set as the defined analytical target profile (ATP) and to this purpose utilization of a switching valve allowed the flow to be sent to waste when rabeprazole was eluted. The selected critical quality attributes (CQAs) were the separation criterion s between the critical peak pair and the capacity factor k of the last eluted compound. The effect of the following critical process parameters (CPPs) on the CQAs was studied: %ACN content, the pH and the concentration of the buffer salt in the mobile phase, as well as the stationary phase of the analytical column. D-Optimal design was implemented to set the plan of experiments with UV detector. In order to define the design space, Monte Carlo simulations with 5000 iterations were performed. Acceptance criteria were met for Cs column (50 x 4 mm, 5 p.m), and the region having probability pi >= 95% to achieve satisfactory values of all defined CQAs was computed. The working point was selected with the mobile phase consisting of ACN, ammonium formate 11 mM at a ratio 31/69 v/v with pH-6,8 for the water phase. The LC 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 = "Analysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method development",
volume = "149",
pages = "410-418",
doi = "10.1016/j.jpba.2017.11.037"
}

Iliou, K., Malenović, A., Loukas, Y. L.,& Dotsikas, Y.. (2018). Analysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method development. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 149, 410-418.
https://doi.org/10.1016/j.jpba.2017.11.037

Iliou K, Malenović A, Loukas YL, Dotsikas Y. Analysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method development. in Journal of Pharmaceutical and Biomedical Analysis. 2018;149:410-418.
doi:10.1016/j.jpba.2017.11.037 .

Iliou, Katerina, Malenović, Anđelija, Loukas, Yannis L., Dotsikas, Yannis, "Analysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method development" in Journal of Pharmaceutical and Biomedical Analysis, 149 (2018):410-418,
https://doi.org/10.1016/j.jpba.2017.11.037 . .

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 . .

TY  - JOUR
AU  - Foivas, Anargyros
AU  - Malenović, Anđelija
AU  - Kostić, Nada
AU  - Božić, Marija
AU  - Knežević, Miroslav
AU  - Loukas, Yannis L.
AU  - Dotsikas, Yannis
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2566
AB  - In the current study, a rapid and sensitive LC-QTOF-MS/MS method for the determination of brinzolamide in dried blood spots (DBS) was developed and validated. This novel sample collection, storage and transfer technique was suitable for analyzing a drug with high distribution into red blood cells and negligible plasma levels. The method included an isocratic mobile phase consisting of methanol and 10 mM ammonium formate (90:10, v/v) and detection in positive electrospray mode (ESI+). The flow rate was adjusted to 0.350 mL/min yielding retention times of 1.7 min for both brinzolamide and internal standard (IS) rabeprazole on a Cyano analytical column, respectively. The validation of the proposed method over the concentration range 0.500-20.0 mu g/mL was performed in compliance with EMEA and FDA guidelines, assessing all major performance characteristics. Inter- and intra- assay precisions were less than 14%, while inter- and intra- assay accuracies varied from 922 to 111%. No matrix effect was observed and the mean brinzolamide extraction recovery was 93.5%. The method was successfully applied to real DBS samples from patients in steady state condition, receiving brinzolamide ophthalmic suspension 1% (w/v) for several months. Initial concentrations were corrected due to hematocrit effect, using image processing algorithm written in Matlab.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method
VL  - 119
SP  - 84
EP  - 90
DO  - 10.1016/j.jpba.2015.11.043
ER  - 

@article{
author = "Foivas, Anargyros and Malenović, Anđelija and Kostić, Nada and Božić, Marija and Knežević, Miroslav and Loukas, Yannis L. and Dotsikas, Yannis",
year = "2016",
abstract = "In the current study, a rapid and sensitive LC-QTOF-MS/MS method for the determination of brinzolamide in dried blood spots (DBS) was developed and validated. This novel sample collection, storage and transfer technique was suitable for analyzing a drug with high distribution into red blood cells and negligible plasma levels. The method included an isocratic mobile phase consisting of methanol and 10 mM ammonium formate (90:10, v/v) and detection in positive electrospray mode (ESI+). The flow rate was adjusted to 0.350 mL/min yielding retention times of 1.7 min for both brinzolamide and internal standard (IS) rabeprazole on a Cyano analytical column, respectively. The validation of the proposed method over the concentration range 0.500-20.0 mu g/mL was performed in compliance with EMEA and FDA guidelines, assessing all major performance characteristics. Inter- and intra- assay precisions were less than 14%, while inter- and intra- assay accuracies varied from 922 to 111%. No matrix effect was observed and the mean brinzolamide extraction recovery was 93.5%. The method was successfully applied to real DBS samples from patients in steady state condition, receiving brinzolamide ophthalmic suspension 1% (w/v) for several months. Initial concentrations were corrected due to hematocrit effect, using image processing algorithm written in Matlab.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method",
volume = "119",
pages = "84-90",
doi = "10.1016/j.jpba.2015.11.043"
}

Foivas, A., Malenović, A., Kostić, N., Božić, M., Knežević, M., Loukas, Y. L.,& Dotsikas, Y.. (2016). Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 119, 84-90.
https://doi.org/10.1016/j.jpba.2015.11.043

Foivas A, Malenović A, Kostić N, Božić M, Knežević M, Loukas YL, Dotsikas Y. Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method. in Journal of Pharmaceutical and Biomedical Analysis. 2016;119:84-90.
doi:10.1016/j.jpba.2015.11.043 .

Foivas, Anargyros, Malenović, Anđelija, Kostić, Nada, Božić, Marija, Knežević, Miroslav, Loukas, Yannis L., Dotsikas, Yannis, "Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method" in Journal of Pharmaceutical and Biomedical Analysis, 119 (2016):84-90,
https://doi.org/10.1016/j.jpba.2015.11.043 . .