The effect of eluent pH and compound acid–base character on the design of generic-gradient reversed-phase high-performance liquid chromatography (RP-HPLC) methods for use in drug discovery

Law, Brian K.

doi:10.1016/j.japna.2003.07.005

Cited by 7 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chromatographically valid data of gradient pH conditions considering the generic elution gradients with a very high number of compounds is described in the literature by Law (2004), resulting in a conclusion that gradient elution at neutral pH conditions is highly successful for most compounds, as long as logD values of the analytes are > –2. If the pH is increased above 8, the chromatographic performance for acidic compounds is weakened, whereas the pH below 4 decreases the performance with basic compounds.…”

Section: Introductionmentioning

confidence: 99%

“…The ECVAM list of validation compounds is not based on chemical classes (acids, bases, neutrals, amphoterics) but rather on the different toxicities of the compounds. For this reason the final set contained a relatively high number of chemically neutral compounds, so that this class of compounds was present in a clearly higher proportion than neutral compounds in drug discovery in general (Law, 2004). However, as the multiresidual techniques are nowadays of high importance in several analytical fields, such as metabolism, environmental and forensic sciences, or plant and human metabolomics, the search of compromise between optimal conditions for chromatographic separation, and detection is of great interest also in the application areas other than drug metabolism studies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Applicability of generic assays based on liquid chromatography–electrospray mass spectrometry to study in vitro metabolism of 55 structurally diverse compounds

Rousu¹

2010

Front. Pharmacol.

View full text Add to dashboard Cite

Liquid chromatography–mass spectrometry (LC–MS) with generic gradient elution for a large number of chemically different compounds is a common approach in drug development, used to acquire a large amount of data in a short time frame for drug candidates. The analysis with non-optimized parameters however may lead to a poor method performance for many compounds, and contains a risk of losing important information. Here, generic electrospray time of flight (ESI-TOF) MS methods in various pH conditions were tested for 55 chemically diverse compounds (10 acids, 25 bases, 17 neutrals, and 3 amphoterics), aiming to find best analytical conditions for each compound, for studies of in vitro metabolic properties in liver preparations. The effect of eluent pH and elution gradient strength on chromatographic performance and electrospray MS ionization efficiency were examined for each compound. The data are evaluated how well the best generic approach could cover the analysis of test compounds and how many compounds would still need completely different analytical conditions after that. Aqueous mobile phase consisting of 0.05% acetic acid and 5 mM ammonium acetate (pH 4.4) showed the best general suitability for the analyses, showing adequate performance for metabolite profiling for 41 out of 55 compounds either in positive or negative ion mode. In positive ion mode, the main limitation of performance in various pH conditions was generally not the lack of ionization, but rather the poor chromatographic performance (inadequate retention or poor peak shape), suggesting that more emphasis should be put in finding conditions providing best chromatographic performance, rather than highest ionization properties. However, a single generic approach for a large number of different compounds is not likely to produce good results for all compounds. Preferably, at least two or three different conditions are needed for the coverage of a larger number of structurally diverse compounds.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Applicability of generic assays based on liquid chromatography–electrospray mass spectrometry to study in vitro metabolism of 55 structurally diverse compounds

Rousu¹

2010

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

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

Molina-Martin¹,

Marín²,

Rivera‐Sagredo³

et al. 2005

J of Separation Science

View full text Add to dashboard Cite

The combination of HPLC and MS has become the most valuable analytical tool to determine the identity and purity of a drug substance in the drug discovery arena over the past decade. This article describes different LC/MS configurations and their broad applicability to meet the fundamental analytical requirements involved in discovering new drugs. In addition, the value of chemiluminescence nitrogen detection for absolute purity determination and the convenience of CE as an orthogonal separation technique to HPLC are also discussed. In summary, LC/MS-based methodologies that implicate automation, various levels of throughput and open access systems have proved to be an integral part of the drug discovery process. As a result, the paradigm of high-quality/-quantity information is fulfilled in a timely fashion.

show abstract

Retention Characteristics of Four Different HILIC Stationary Phases in the Analysis of Meat Polar Compounds

2011

View full text Add to dashboard Cite

The effect of eluent pH and compound acid–base character on the design of generic-gradient reversed-phase high-performance liquid chromatography (RP-HPLC) methods for use in drug discovery

Cited by 7 publications

References 18 publications

Applicability of generic assays based on liquid chromatography–electrospray mass spectrometry to study in vitro metabolism of 55 structurally diverse compounds

Applicability of generic assays based on liquid chromatography–electrospray mass spectrometry to study in vitro metabolism of 55 structurally diverse compounds

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

Retention Characteristics of Four Different HILIC Stationary Phases in the Analysis of Meat Polar Compounds

Contact Info

Product

Resources

About