Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies

The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies. The critical method parameters (CMPs) have been tested extensively: the kind of stationary phase (8 different columns), pH of the aqueous mobile phase (2.6, 3.2, 4.0, 6.8), and start (20–25%) and stop (85–90%) percentage of organic mobile phase (ACN). The critical method attributes (CMAs) are the resolution between the peaks (≥2.0) and peak symmetry of analytes (≥0.8 and ≤1.8). In the screening step, the effects of different levels of CMPs on the CMAs were evaluated based on a full fractional design 2<sup<2</sup<. The robustness tests were established from the knowledge space of the screening step and performed by application fractional factorial design 2<sup<(4−1)</sup<. Method operable design region (MODR) was generated. The probability of meeting the specifications for the CMAs was calculated by Monte-Carlo simulations. In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Lidia Gurba-Bryśkiewicz [verfasserIn] Urszula Dawid [verfasserIn] Damian A. Smuga [verfasserIn] Wioleta Maruszak [verfasserIn] Monika Delis [verfasserIn] Krzysztof Szymczak [verfasserIn] Bartosz Stypik [verfasserIn] Aleksandra Moroz [verfasserIn] Aleksandra Błocka [verfasserIn] Michał Mroczkiewicz [verfasserIn] Krzysztof Dubiel [verfasserIn] Maciej Wieczorek [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Analytical Quality by Design (AQbD) design of experiment (DOE) method operable design region (MODR) pharmaceutical impurity profiling analytical method development CHI logD

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 23(2022), 18, p 10720
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:18, p 10720

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms231810720

Katalog-ID:	DOAJ005608104

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allfields	10.3390/ijms231810720 doi (DE-627)DOAJ005608104 (DE-599)DOAJec537747e2e1459bbbfa0941bd7f61dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Lidia Gurba-Bryśkiewicz verfasserin aut Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies. The critical method parameters (CMPs) have been tested extensively: the kind of stationary phase (8 different columns), pH of the aqueous mobile phase (2.6, 3.2, 4.0, 6.8), and start (20–25%) and stop (85–90%) percentage of organic mobile phase (ACN). The critical method attributes (CMAs) are the resolution between the peaks (≥2.0) and peak symmetry of analytes (≥0.8 and ≤1.8). In the screening step, the effects of different levels of CMPs on the CMAs were evaluated based on a full fractional design 2<sup<2</sup<. The robustness tests were established from the knowledge space of the screening step and performed by application fractional factorial design 2<sup<(4−1)</sup<. Method operable design region (MODR) was generated. The probability of meeting the specifications for the CMAs was calculated by Monte-Carlo simulations. In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities. Analytical Quality by Design (AQbD) design of experiment (DOE) method operable design region (MODR) pharmaceutical impurity profiling analytical method development CHI logD Biology (General) Chemistry Urszula Dawid verfasserin aut Damian A. Smuga verfasserin aut Wioleta Maruszak verfasserin aut Monika Delis verfasserin aut Krzysztof Szymczak verfasserin aut Bartosz Stypik verfasserin aut Aleksandra Moroz verfasserin aut Aleksandra Błocka verfasserin aut Michał Mroczkiewicz verfasserin aut Krzysztof Dubiel verfasserin aut Maciej Wieczorek verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10720 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10720 https://doi.org/10.3390/ijms231810720 kostenfrei https://doaj.org/article/ec537747e2e1459bbbfa0941bd7f61dd kostenfrei https://www.mdpi.com/1422-0067/23/18/10720 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10720
spelling	10.3390/ijms231810720 doi (DE-627)DOAJ005608104 (DE-599)DOAJec537747e2e1459bbbfa0941bd7f61dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Lidia Gurba-Bryśkiewicz verfasserin aut Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies. The critical method parameters (CMPs) have been tested extensively: the kind of stationary phase (8 different columns), pH of the aqueous mobile phase (2.6, 3.2, 4.0, 6.8), and start (20–25%) and stop (85–90%) percentage of organic mobile phase (ACN). The critical method attributes (CMAs) are the resolution between the peaks (≥2.0) and peak symmetry of analytes (≥0.8 and ≤1.8). In the screening step, the effects of different levels of CMPs on the CMAs were evaluated based on a full fractional design 2<sup<2</sup<. The robustness tests were established from the knowledge space of the screening step and performed by application fractional factorial design 2<sup<(4−1)</sup<. Method operable design region (MODR) was generated. The probability of meeting the specifications for the CMAs was calculated by Monte-Carlo simulations. In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities. Analytical Quality by Design (AQbD) design of experiment (DOE) method operable design region (MODR) pharmaceutical impurity profiling analytical method development CHI logD Biology (General) Chemistry Urszula Dawid verfasserin aut Damian A. Smuga verfasserin aut Wioleta Maruszak verfasserin aut Monika Delis verfasserin aut Krzysztof Szymczak verfasserin aut Bartosz Stypik verfasserin aut Aleksandra Moroz verfasserin aut Aleksandra Błocka verfasserin aut Michał Mroczkiewicz verfasserin aut Krzysztof Dubiel verfasserin aut Maciej Wieczorek verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10720 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10720 https://doi.org/10.3390/ijms231810720 kostenfrei https://doaj.org/article/ec537747e2e1459bbbfa0941bd7f61dd kostenfrei https://www.mdpi.com/1422-0067/23/18/10720 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10720
allfields_unstemmed	10.3390/ijms231810720 doi (DE-627)DOAJ005608104 (DE-599)DOAJec537747e2e1459bbbfa0941bd7f61dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Lidia Gurba-Bryśkiewicz verfasserin aut Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies. The critical method parameters (CMPs) have been tested extensively: the kind of stationary phase (8 different columns), pH of the aqueous mobile phase (2.6, 3.2, 4.0, 6.8), and start (20–25%) and stop (85–90%) percentage of organic mobile phase (ACN). The critical method attributes (CMAs) are the resolution between the peaks (≥2.0) and peak symmetry of analytes (≥0.8 and ≤1.8). In the screening step, the effects of different levels of CMPs on the CMAs were evaluated based on a full fractional design 2<sup<2</sup<. The robustness tests were established from the knowledge space of the screening step and performed by application fractional factorial design 2<sup<(4−1)</sup<. Method operable design region (MODR) was generated. The probability of meeting the specifications for the CMAs was calculated by Monte-Carlo simulations. In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities. Analytical Quality by Design (AQbD) design of experiment (DOE) method operable design region (MODR) pharmaceutical impurity profiling analytical method development CHI logD Biology (General) Chemistry Urszula Dawid verfasserin aut Damian A. Smuga verfasserin aut Wioleta Maruszak verfasserin aut Monika Delis verfasserin aut Krzysztof Szymczak verfasserin aut Bartosz Stypik verfasserin aut Aleksandra Moroz verfasserin aut Aleksandra Błocka verfasserin aut Michał Mroczkiewicz verfasserin aut Krzysztof Dubiel verfasserin aut Maciej Wieczorek verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10720 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10720 https://doi.org/10.3390/ijms231810720 kostenfrei https://doaj.org/article/ec537747e2e1459bbbfa0941bd7f61dd kostenfrei https://www.mdpi.com/1422-0067/23/18/10720 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10720
allfieldsGer	10.3390/ijms231810720 doi (DE-627)DOAJ005608104 (DE-599)DOAJec537747e2e1459bbbfa0941bd7f61dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Lidia Gurba-Bryśkiewicz verfasserin aut Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies. The critical method parameters (CMPs) have been tested extensively: the kind of stationary phase (8 different columns), pH of the aqueous mobile phase (2.6, 3.2, 4.0, 6.8), and start (20–25%) and stop (85–90%) percentage of organic mobile phase (ACN). The critical method attributes (CMAs) are the resolution between the peaks (≥2.0) and peak symmetry of analytes (≥0.8 and ≤1.8). In the screening step, the effects of different levels of CMPs on the CMAs were evaluated based on a full fractional design 2<sup<2</sup<. The robustness tests were established from the knowledge space of the screening step and performed by application fractional factorial design 2<sup<(4−1)</sup<. Method operable design region (MODR) was generated. The probability of meeting the specifications for the CMAs was calculated by Monte-Carlo simulations. In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities. Analytical Quality by Design (AQbD) design of experiment (DOE) method operable design region (MODR) pharmaceutical impurity profiling analytical method development CHI logD Biology (General) Chemistry Urszula Dawid verfasserin aut Damian A. Smuga verfasserin aut Wioleta Maruszak verfasserin aut Monika Delis verfasserin aut Krzysztof Szymczak verfasserin aut Bartosz Stypik verfasserin aut Aleksandra Moroz verfasserin aut Aleksandra Błocka verfasserin aut Michał Mroczkiewicz verfasserin aut Krzysztof Dubiel verfasserin aut Maciej Wieczorek verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10720 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10720 https://doi.org/10.3390/ijms231810720 kostenfrei https://doaj.org/article/ec537747e2e1459bbbfa0941bd7f61dd kostenfrei https://www.mdpi.com/1422-0067/23/18/10720 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10720
allfieldsSound	10.3390/ijms231810720 doi (DE-627)DOAJ005608104 (DE-599)DOAJec537747e2e1459bbbfa0941bd7f61dd DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Lidia Gurba-Bryśkiewicz verfasserin aut Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies. The critical method parameters (CMPs) have been tested extensively: the kind of stationary phase (8 different columns), pH of the aqueous mobile phase (2.6, 3.2, 4.0, 6.8), and start (20–25%) and stop (85–90%) percentage of organic mobile phase (ACN). The critical method attributes (CMAs) are the resolution between the peaks (≥2.0) and peak symmetry of analytes (≥0.8 and ≤1.8). In the screening step, the effects of different levels of CMPs on the CMAs were evaluated based on a full fractional design 2<sup<2</sup<. The robustness tests were established from the knowledge space of the screening step and performed by application fractional factorial design 2<sup<(4−1)</sup<. Method operable design region (MODR) was generated. The probability of meeting the specifications for the CMAs was calculated by Monte-Carlo simulations. In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities. Analytical Quality by Design (AQbD) design of experiment (DOE) method operable design region (MODR) pharmaceutical impurity profiling analytical method development CHI logD Biology (General) Chemistry Urszula Dawid verfasserin aut Damian A. Smuga verfasserin aut Wioleta Maruszak verfasserin aut Monika Delis verfasserin aut Krzysztof Szymczak verfasserin aut Bartosz Stypik verfasserin aut Aleksandra Moroz verfasserin aut Aleksandra Błocka verfasserin aut Michał Mroczkiewicz verfasserin aut Krzysztof Dubiel verfasserin aut Maciej Wieczorek verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10720 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10720 https://doi.org/10.3390/ijms231810720 kostenfrei https://doaj.org/article/ec537747e2e1459bbbfa0941bd7f61dd kostenfrei https://www.mdpi.com/1422-0067/23/18/10720 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10720
language	English
source	In International Journal of Molecular Sciences 23(2022), 18, p 10720 volume:23 year:2022 number:18, p 10720
sourceStr	In International Journal of Molecular Sciences 23(2022), 18, p 10720 volume:23 year:2022 number:18, p 10720
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Analytical Quality by Design (AQbD) design of experiment (DOE) method operable design region (MODR) pharmaceutical impurity profiling analytical method development CHI logD Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Lidia Gurba-Bryśkiewicz @@aut@@ Urszula Dawid @@aut@@ Damian A. Smuga @@aut@@ Wioleta Maruszak @@aut@@ Monika Delis @@aut@@ Krzysztof Szymczak @@aut@@ Bartosz Stypik @@aut@@ Aleksandra Moroz @@aut@@ Aleksandra Błocka @@aut@@ Michał Mroczkiewicz @@aut@@ Krzysztof Dubiel @@aut@@ Maciej Wieczorek @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ005608104
language_de	englisch
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callnumber-first	Q - Science
author	Lidia Gurba-Bryśkiewicz
spellingShingle	Lidia Gurba-Bryśkiewicz misc QH301-705.5 misc QD1-999 misc Analytical Quality by Design (AQbD) misc design of experiment (DOE) misc method operable design region (MODR) misc pharmaceutical impurity profiling misc analytical method development misc CHI logD misc Biology (General) misc Chemistry Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies
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topic_title	QH301-705.5 QD1-999 Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies Analytical Quality by Design (AQbD) design of experiment (DOE) method operable design region (MODR) pharmaceutical impurity profiling analytical method development CHI logD
topic	misc QH301-705.5 misc QD1-999 misc Analytical Quality by Design (AQbD) misc design of experiment (DOE) misc method operable design region (MODR) misc pharmaceutical impurity profiling misc analytical method development misc CHI logD misc Biology (General) misc Chemistry
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title	Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies
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title_full	Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies
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author_browse	Lidia Gurba-Bryśkiewicz Urszula Dawid Damian A. Smuga Wioleta Maruszak Monika Delis Krzysztof Szymczak Bartosz Stypik Aleksandra Moroz Aleksandra Błocka Michał Mroczkiewicz Krzysztof Dubiel Maciej Wieczorek
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title_sort	implementation of qbd approach to the development of chromatographic methods for the determination of complete impurity profile of substance on the preclinical and clinical step of drug discovery studies
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title_auth	Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies
abstract	The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies. The critical method parameters (CMPs) have been tested extensively: the kind of stationary phase (8 different columns), pH of the aqueous mobile phase (2.6, 3.2, 4.0, 6.8), and start (20–25%) and stop (85–90%) percentage of organic mobile phase (ACN). The critical method attributes (CMAs) are the resolution between the peaks (≥2.0) and peak symmetry of analytes (≥0.8 and ≤1.8). In the screening step, the effects of different levels of CMPs on the CMAs were evaluated based on a full fractional design 2<sup<2</sup<. The robustness tests were established from the knowledge space of the screening step and performed by application fractional factorial design 2<sup<(4−1)</sup<. Method operable design region (MODR) was generated. The probability of meeting the specifications for the CMAs was calculated by Monte-Carlo simulations. In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities.
abstractGer	The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies. The critical method parameters (CMPs) have been tested extensively: the kind of stationary phase (8 different columns), pH of the aqueous mobile phase (2.6, 3.2, 4.0, 6.8), and start (20–25%) and stop (85–90%) percentage of organic mobile phase (ACN). The critical method attributes (CMAs) are the resolution between the peaks (≥2.0) and peak symmetry of analytes (≥0.8 and ≤1.8). In the screening step, the effects of different levels of CMPs on the CMAs were evaluated based on a full fractional design 2<sup<2</sup<. The robustness tests were established from the knowledge space of the screening step and performed by application fractional factorial design 2<sup<(4−1)</sup<. Method operable design region (MODR) was generated. The probability of meeting the specifications for the CMAs was calculated by Monte-Carlo simulations. In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities.
abstract_unstemmed	The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies. The critical method parameters (CMPs) have been tested extensively: the kind of stationary phase (8 different columns), pH of the aqueous mobile phase (2.6, 3.2, 4.0, 6.8), and start (20–25%) and stop (85–90%) percentage of organic mobile phase (ACN). The critical method attributes (CMAs) are the resolution between the peaks (≥2.0) and peak symmetry of analytes (≥0.8 and ≤1.8). In the screening step, the effects of different levels of CMPs on the CMAs were evaluated based on a full fractional design 2<sup<2</sup<. The robustness tests were established from the knowledge space of the screening step and performed by application fractional factorial design 2<sup<(4−1)</sup<. Method operable design region (MODR) was generated. The probability of meeting the specifications for the CMAs was calculated by Monte-Carlo simulations. In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities.
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title_short	Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies
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In relation to literature such a complete AQbD approach including screening, optimization, and validation steps for the development of a new method for the quantitative determination of the full profile of nine impurities of an innovative pharmaceutical substance with the structure-based pre-development pointed out the novelty of our work. The final working conditions were as follows: column Zorbax Eclipse Plus C18, aqueous mobile phase 10 mM ± 1 mM aqueous solution of HCOOH, pH 2.6, 20% ± 1% of ACN at the start and 85% ± 1% of ACN at the end of the gradient, and column temperature 30 °C ± 2 °C. The method was validated in compliance with ICH guideline Q2(R1). The optimized method is specified, linear, precise, and robust. 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Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies

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