Application of Quality by Design to optimize a stability-indicating LC method for the determination of ticagrelor and its impurities

Wingert, Nathalie Ribeiro; Ellwanger, Jéssica Bauer; Bueno, Lívia Maronesi; Gobetti, Caren; Garcia, Cássia Virgínia; Steppe, Martin; Schapoval, Elfrides Eva Scherman

doi:10.1016/j.ejps.2018.03.029

Cited by 29 publications

(11 citation statements)

References 19 publications

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“…The study involved a quality‐by‐design approach in method optimization. The developed and validated HPLC method with UV detection was able to resolve the eight chemically related compounds in <3 min (Wingert et al, ). The analytical characteristics of the above cited HPLC methods are presented in brief in Table .…”

Section: Methodsmentioning

confidence: 99%

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Analytical methodologies for the determination of ticagrelor

Kelemen

Hancu

Papp

2019

Biomedical Chromatography

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Ticagrelor is an orally administered platelet aggregation inhibitor with a cyclopentyl‐triazolopyrimidine structure; it is a selective reversible P2Y12 receptor antagonist, which prevents P2Y12‐mediated and ADP‐mediated platelet activation and aggregation. It is used to reduce the rate of cardiovascular death, myocardial infarction and stroke in patients with acute coronary syndrome or history of myocardial infarction. Several analytical methods have been published for the determination of ticagrelor in pharmaceuticals and biological materials by spectrophotometry, high‐performance liquid chromatography with ultraviolet detection and liquid chromatography coupled with tandem mass spectrometry. The purpose of the current review is to provide a systematic survey of the analytical techniques used for the determination of ticagrelor since its introduction in therapy until today.

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Section: Methodsmentioning

confidence: 99%

“…Wingert et al (2018) TCG, Ticagrelor (1S,2S,3R,5S)-3-{7-[(1R,2S)-2-(3,4-difluorophenyl)cyclopropylamino]-5-(propylthio)-3H-(1,2,3)triazolo(4,5-D)pyrimidin-3-yl}-5-(2-hydroxyethoxy)cyclopentane-1,2-diol.…”

mentioning

confidence: 99%

Analytical methodologies for the determination of ticagrelor

Kelemen

Hancu

Papp

2019

Biomedical Chromatography

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“…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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Application of Quality by Design to optimize a stability-indicating LC method for the determination of ticagrelor and its impurities

Cited by 29 publications

References 19 publications

Analytical methodologies for the determination of ticagrelor

Analytical methodologies for the determination of ticagrelor

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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