Generic anion-exchange chromatography method for analytical and preparative separation of nucleotides in the development and manufacture of drug substances

Tsay, Fuh‐Rong; Ahmad, Imad A. Haidar; Henderson, Derek; Schiavone, Nicole M.; Liu, Zhijian; Makarov, Alexey A.; Mangion, Ian; Regalado, Erik L.

doi:10.1016/j.chroma.2018.12.018

Cited by 26 publications

(22 citation statements)

References 38 publications

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“…Some procedures are already present in the literature [23,24], however, to increase their simplicity in silico modeling can represent a helpful addition. Computer-assisted modeling of retention time has become a powerful tool to accelerate method development for both analytical and preparative scale separations [1,18,[25][26][27][28][29]. The inclusion of such a strategy could facilitate a streamlined study of column performance and stability across multiple stationary and mobile phase selectivity.…”

Section: Introductionmentioning

confidence: 99%

Generic reversed‐phase ultra‐high‐pressure liquid chromatography methodology developed by using computer‐assisted modeling for streamlined performance evaluation of a wide range of stationary phase columns

Ahmad

Losacco

Figus

et al. 2022

Separation Science Plus

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Selection of column and mobile phase eluent/buffer is a crucial step in chromatographic method development. The introduction of new column technologies requires a continuous performance evaluation enabling the deployment of improved chromatographic screening workflows. Consequently, the development of a universal method that could be used across different column chemistries and mobile phase pH ranges would be highlighted as advantageous.Herein, we introduce a single generic probe developed via software-based modeling that delivers excellent results for the separation of a standard multicomponent mixture across a wide range of stationary phases under different pH and temperature conditions. This approach has been applied to interrogate the performance and stability of multiple columns (C18, Cyano, Phenyl Hexyl, PFP, Polar-embeded, and other stationary phases) using an automated ultra-highpressure liquid chromatography screening system illustrating its practicality and effectiveness.

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Section: Introductionmentioning

confidence: 99%

Generic reversed‐phase ultra‐high‐pressure liquid chromatography methodology developed by using computer‐assisted modeling for streamlined performance evaluation of a wide range of stationary phase columns

Ahmad

Losacco

Figus

et al. 2022

Separation Science Plus

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“…This is a cost-effective and time-efficient approach that translates into a rapid turnaround of results which is vital to accelerating process development and manufacturing of new drug substances. Some examples include the analysis of solvents and volatile amines by gas chromatography (GC), ,,,, a generic method for nucleotides and palladium scavengers by ion exchange chromatography (IEC), dehalogenation impurities and mixtures of halogen isomers, ,− drug metabolites and analogues, − direct analysis of chiral active pharmaceutical ingredients (APIs) and their counterions by UHPLC, enantiopurity analysis across an entire synthetic route using a single chiral core–shell column in LC mode, generic chiral method development in SFC, and synthetic intermediates containing multiple stereocenters by two-dimensional LC, among others …”

Section: Introductionmentioning

confidence: 99%

Generic Enhanced Sub/Supercritical Fluid Chromatography: Blueprint for Highly Productive and Sustainable Separation of Primary Hindered Amines

DaSilva

Lehnherr

Liu

et al. 2020

ACS Sustainable Chem. Eng.

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α,α-Diaryl primary amines are highly important chemical building blocks in agrochemical and pharmaceutical active ingredients. One of the limitations of current chromatographic methodologies for these molecules is the poor greenness factor as a result of high solvent consumption to reach the necessary productivity, as well as the lack of systematic approaches. Herein, we overcome these challenges by introducing a simple and highly efficient enhanced sub/supercritical fluid chromatography (eSFC) approach that enables analysis and purification of over 40 α,α-diaryl primary amine mixtures. This approach translates into several highly desirable features from a simplicity and greenness perspective including (1) improved chromatographic performance and productivity, (2) augmented MS detection that allows for analytical eSFC−MS and preparative MS-directed purifications, and (3) efficient and direct solvent removal. This strategy represents a move toward modernized greener and sustainable separations as demonstrated by a 30-fold improvement of the analytical method greenness score (AMGS) compared to currently available chromatographic approaches.

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“…The development and validation of generic or more universal chromatographic methods has proliferated in both academia and industry. − Such generic chromatographic methodologies can be successfully applied to minimize the time spent developing new analytical assays prior to each analysis session while streamlining method transfer to manufacturing facilities. In this study, a new systematic approach for the analysis of over 10 of the most commonly used Pd scavengers in a single chromatographic run is reported.…”

Section: Introductionmentioning

confidence: 99%

Generic Ion Chromatography–Conductivity Detection Method for Analysis of Palladium Scavengers in New Drug Substances

Zou

Bennett

Ahmad

et al. 2019

Org. Process Res. Dev.

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The revolution of palladium-catalyzed reactions in the synthesis of new molecules has created an unprecedented need for highly efficient palladium (Pd) removal processes. Metal scavengers with very selective and efficient removal properties are being extensively applied across process research and development (PR&D) to meet very tight specifications for residual Pd levels. Analytical procedures for the determination of residual Pd are well-established; however, developing methodologies to detect a variety of Pd scavengers in multicomponent reaction mixtures is currently considered an emerging challenge in pharmaceutical analysis. Herein a simple and efficient generic ion chromatography−conductivity detection (IC−CD) method on a Dionex IonPac AS19 column in conjunction with a fully aqueous eluent profile (potassium-hydroxide-based) capable of chromatographically resolving over 10 Pd scavenger species commonly used in PR&D workflows is described. Computerassisted separation modeling using an ACD Labs/LC simulator served to generate 3D resolution maps with excellent separation conditions that matched the outcome of subsequent experimental data. Method validation experiments showed excellent analytical performance in linearity, recovery, repeatability, and LOQ/LOD. In addition, these same chromatographic conditions can separate multiple anionic species and active pharmaceutical (API) counterions along with Pd scavengers in the same experimental run. We also provide strategic examples where API counterion interferences (e.g., sulfate) can be minimized by treating the API sulfate form with barium acetate to enhance the recovery of the Pd scavenger analyte.

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Generic anion-exchange chromatography method for analytical and preparative separation of nucleotides in the development and manufacture of drug substances

Cited by 26 publications

References 38 publications

Generic reversed‐phase ultra‐high‐pressure liquid chromatography methodology developed by using computer‐assisted modeling for streamlined performance evaluation of a wide range of stationary phase columns

Generic reversed‐phase ultra‐high‐pressure liquid chromatography methodology developed by using computer‐assisted modeling for streamlined performance evaluation of a wide range of stationary phase columns

Generic Enhanced Sub/Supercritical Fluid Chromatography: Blueprint for Highly Productive and Sustainable Separation of Primary Hindered Amines

Generic Ion Chromatography–Conductivity Detection Method for Analysis of Palladium Scavengers in New Drug Substances

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