Liquid chromatography‐mass spectrometry and related techniques for purity assessment in early drug discovery

Molina-Martin, Manuel; Marín, A.; Rivera‐Sagredo, Alfonso; Espada, Alfonso

doi:10.1002/jssc.200500107

Cited by 13 publications

(11 citation statements)

References 31 publications

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“…While in the development stage a limited number of samples are analyzed in significant detail, scientists in the discovery stage are faced with the need to provide purity assessment for thousands of compounds on a monthly, if not weekly, basis [59,60]. In addition, impurity profiling in drug development is mainly a tool to understand and above all gain control over the production process and in addition to prove the safety of the total product.…”

Section: Purity Analysis and Impurity Profilingmentioning

confidence: 99%

“…An exact reproduction of the impurity profile of the various "discovery batches" is of lesser importance; in case of unexplained findings, the identity of impurities can be requested. In contrast to the drug development stages, the large diversity in chemical structures and structural properties, in combination with the required short analysis times, has led to the introduction of more "generic" high-throughput HPlC-uV-MS platforms for this purpose [60]. While HPlC-uV-MS has become very useful for drug purity screening, there are some practical considerations that should be understood.…”

Section: Purity Analysis and Impurity Profilingmentioning

confidence: 99%

“…The latter interface showed its usefulness in the analysis of rather nonpolar steroidal molecules. Despite these developments, HPlC-MS platforms supporting purity analysis or impurity profiling are typically hyphenated with uV-VIS (DAD), evaporative light scattering detection (ElSD), or chemiluminescent nitrogen detector (ClND) type of detectors that provide a normalized detector response for an extreme broad range of molecular structures [60].…”

Section: Purity Analysis and Impurity Profilingmentioning

confidence: 99%

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MS Applications in Support of Medicinal Chemistry Sciences

Honing¹,

Ingelse²,

Pramanik³

2013

Mass Spectrometry for Drug Discovery and Drug Development

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In the drug discovery process, medicinal chemistry plays a crucial role in the optimal design and synthesis (production) of new chemical entities (NCEs) or new biological entities (NBEs); this is true for a single entity as well as a complete compound library. A key requirement in this field of science is the optimization of both the chemical and the biological properties of these potential drug-like compounds. Important criteria are the design of efficient synthesis routes, the balancing of the physical chemical properties with optimal in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) processes, and a profound understanding of the pharmacodynamics in the appropriate pharmacological models. In the lead optimization stage, an important step is scaling up the synthesis route as needed for the execution of toxicology studies and the screening of suitable drug formulations. In summary, medicinal chemistry support includes participating in a large variety of activities and decision making processes that play a key role in the search for either a "first in class" new drug or a "best in class" new drug [1].These "drug discovery" processes are continuously under pressure, as the research and development (R&D) costs continue to increase and more data are requested before new drug candidates are taken into (pre-)clinical development. Hence, the choice of "targeted" high-throughput screening (HTS) libraries, the process of hit appraisal, and the understanding of target-ligand interactions can be considered the starting points for a new drug discovery program [2]. Next, the main focus is on the discovery of a lead compound; typically, this is a compound showing promising data regarding target affinity, reasonable efficacy in cellular models, good physical chemical parameters (i.e., a "drug-like" compound), and acceptable oral bioavailability in Mass Spectrometry for Drug Discovery and Drug Development, First Edition. Edited by Walter A. Korfmacher.

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Section: Purity Analysis and Impurity Profilingmentioning

confidence: 99%

Section: Purity Analysis and Impurity Profilingmentioning

confidence: 99%

Section: Purity Analysis and Impurity Profilingmentioning

confidence: 99%

See 1 more Smart Citation

MS Applications in Support of Medicinal Chemistry Sciences

Honing¹,

Ingelse²,

Pramanik³

2013

Mass Spectrometry for Drug Discovery and Drug Development

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show abstract

“…However purity requirements and analytical procedures differ according to the drug discovery stage from chemical synthesis to compound selection for development (2,3). Whereas in later stages of pharmaceutical development, individually validated methods for each active pharmaceutical ingredient (API) are necessary and required by regulators, such an approach is not practical in earlier stages of discovery and generic methods applicable to a range of compounds must be used to deliver acceptable analysis rates.…”

Section: Introductionmentioning

confidence: 99%

Standardization of Analytical Methodology and Procedures for Purity Assessment of Small Molecules in Drug Discovery

Marín

Sharman

Burgess

et al. 2014

ACS Symposium Series

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“…For instance, it has been found that the use of orthogonal separation procedures reduces the risk of incorrect purity assessment of drug compounds and ensures the quality and safety of drug products. This can be achieved by changing pH, organic solvents, aqueous buffer and stationary phases [13][14][15][16]. Several elegant approaches have been used to automate this method searching.…”

Section: Introductionmentioning

confidence: 99%