Structure assisted impurity profiling for rapid method development in liquid chromatography

Schmidtsdorff, Sebastian; Schmidt, Alexander H.; Parr, Maria Kristina

doi:10.1016/j.chroma.2018.09.044

Cited by 10 publications

(10 citation statements)

References 21 publications

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“…Schmidtsdorff et al used an AQbD approach (Figure ) for optimization and robustness testing of a newly developed HPLC method for separation of carbamazepine and its seven impurities. The goal of the optimization step was to develop a faster method ( t ≤ 30 min) with better separation performance ( R s ≥ 2.0) than the monograph method and with high robustness.…”

Section: Recent Applications Of Aqbd To Lc Methods Developmentmentioning

confidence: 99%

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Development and Optimization of Liquid Chromatography Analytical Methods by Using AQbD Principles: Overview and Recent Advances

Tome

Žigart

Časar

et al. 2019

Org. Process Res. Dev.

130

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This review presents the Analytical Quality by Design (AQbD) concept, an extension of Quality by Design (QbD), which was introduced in 2004 by the U.S. Food and Drug Administration (FDA) and approved in 2005 by the International Conference on Harmonisation (ICH). AQbD is a systematic approach to method development, controlling all stages of the analytical procedure life cycle. It includes a definition of the analytical target profile (ATP), identification of critical method parameters or factors, and selection of critical method attributes (CMAs) or responses. Screening and response-surface experimental designs allow the recognition of significant factors and their optimization by statistical analysis. The factor− response relationship is described by a mathematical model, which is able to predict the optimal response. Multivariate combinations of factors fulfilling the CMA requirements are presented in the design space or method operable design region (MODR), where robust method performance is ensured. This review presents the theoretical background of AQbD for method development and its workflow through recently published cases in which the AQbD concept proved to be a reliable and effective approach. Analytical methods developed by using the AQbD approach are highly robust, are easily validated, have shorter run times, and are capable of determining a higher number of analytes in one run compared with the methods developed by the one-factor-at-a-time (OFAT) approach.

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Section: Recent Applications Of Aqbd To Lc Methods Developmentmentioning

confidence: 99%

“…Schematic presentation of the AQbD workflow in the case of carbamazepine and its seven impurities as presented by Schmidtsdorff et al An isocratic PhEur method with a run time of 110 min was optimized using DryLab 4, leading to a robust method with a 30 min long gradient.…”

Section: Recent Applications Of Aqbd To Lc Methods Developmentmentioning

confidence: 99%

Development and Optimization of Liquid Chromatography Analytical Methods by Using AQbD Principles: Overview and Recent Advances

Tome

Žigart

Časar

et al. 2019

Org. Process Res. Dev.

130

View full text Add to dashboard Cite

show abstract

“…Recently, many publications have been reported discussing the AQbD approach to the development and optimization of HPLC methods, for the determination of either active pharmaceutical ingredient or impurities [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. Indeed, AQbD has turned out to be a reliable and effective approach, which is reflected in these methods, because they are more robust, easily validated, and have shorter run times for the separation of the same number of analytes compared to methods developed using the one-factor-at-a-time (OFAT) approach [26].…”

Section: Introductionmentioning

confidence: 99%

Development of a Unified Reversed-Phase HPLC Method for Efficient Determination of EP and USP Process-Related Impurities in Celecoxib Using Analytical Quality by Design Principles

2020

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This article presents the development of a reversed-phase (RP) high-performance liquid chromatographic (HPLC) method for determination of process-related impurities in a celecoxib drug substance following Analytical Quality by Design (AQbD) principles. The method from European Pharmacopeia (EP) for celecoxib drug substance does not sufficiently separate celecoxib from its EP impurity B because the system suitability criterion is not achieved (resolution NLT 1.8). The same issue was observed with the proposed method from United States Pharmacopeia (USP) for celecoxib capsules, where EP impurity A elutes under the main peak. A new HPLC method was developed that eliminates the disadvantages of the two pharmacopeial methods and is capable of efficiently separating and determining all seven impurities listed in EP and the proposed USP monographs. The development of a new HPLC method started with method scouting, in which various C18 and phenyl stationary phases were tested. Improved selectivity was obtained only with a chiral stationary phase. An immobilized Chiralpak IA-3 column used in RP mode turned out to be the most appropriate for method optimization. The ratio of acetonitrile in the mobile phase, flow rate, and column temperature were recognized as critical method parameters (CMPs) and were further investigated using a central composite face response-surface design. A multiple linear regression (MLR) method was applied to fit the mathematical models on the experimental data to determine factor–response relationships. The models created show adequate fit and good prediction abilities. The Monte Carlo simulation method was used to establish the design space. The method developed was verified in terms of precision, sensitivity, accuracy, and linearity, and the results showed that the new method is suitable for determination of seven process-related impurities of celecoxib.

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“…With the AQbD approach, improved method performance with a defined area of method robustness can be accomplished. Therefore, utilization of AQbD concepts in developing liquid chromatographic methods for determining either active pharmaceutical ingredients or their impurities have flourished in recent years, as evidenced by numerous reports on their successful application [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. The use of AQbD concepts in liquid chromatography method development renders these methods more robust, makes possible their facile validation, and frequently provides shorter run times for the separation of the same number of analytes compared to methods developed using the one-factor-at-a-time (OFAT) approach [25].…”

Section: Introductionmentioning

confidence: 99%

Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles

2020

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This article presents the development of a reversed-phase ultra-high-performance liquid chromatographic method for determining process-related impurities in ropinirole hydrochloride drug substance applying the analytical quality by design approach. The current pharmacopeial method suffers from selectivity issues due to two coelutions of two pairs of impurities. The development of a new method began with preliminary experiments, based on which the Acquity UPLC BEH C8 was selected as the most appropriate column. The effects of six different critical method parameters (CMPs) were then investigated using a fractional factorial screening design. Column temperature, the ratio of methanol in mobile phase B, and gradient slope turned out to be highly significant CMPs in achieving critical resolutions, and they were further evaluated using a central composite face-centered response-surface design. Mathematical models were created by applying a multiple linear regression method. Based on the elution order of an unknown degradation impurity and impurity C, two design spaces were established, and for each design space an optimal combination of CMPs was determined. The method developed was validated for precision, accuracy, linearity, and sensitivity, and it was proven suitable for determining nine process-related impurities of ropinirole.

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Structure assisted impurity profiling for rapid method development in liquid chromatography

Cited by 10 publications

References 21 publications

Development and Optimization of Liquid Chromatography Analytical Methods by Using AQbD Principles: Overview and Recent Advances

Development and Optimization of Liquid Chromatography Analytical Methods by Using AQbD Principles: Overview and Recent Advances

Development of a Unified Reversed-Phase HPLC Method for Efficient Determination of EP and USP Process-Related Impurities in Celecoxib Using Analytical Quality by Design Principles

Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles

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