Putting mass spectrometry in the hands of the end user

Pullen, Frank S.; Perkins, George L.; Burton, Keith I.; Ware, R.; Teague, Mathew S.; Kiplinger, Jeffrey P.

doi:10.1016/1044-0305(95)00028-c

Cited by 44 publications

(27 citation statements)

References 11 publications

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“…We recommend that samples are made up with an analyte concentration of 0.1 mg ml 1 , but even at these concentrations the dead channel effect can occur. Intense signals suppress the response generated at the microchannel plate of those ions arriving slightly later.…”

Section: Resultsmentioning

confidence: 98%

“…Our experience is that time spent setting up flexible, user-friendly and robust open-access systems with readily interpretable output is a particularly worthwhile investment. By coupling mass spectrometry with high-performance liquid chromatography (HPLC), 1 it is possible to offer a comprehensive array of liquid chromatography/mass spectrometry (LC/MS) and flow injection analysis (FIA) tools. 2 Efficient sample introduction via HPLC is even applicable to complementary analytical techniques, such as NMR spectroscopy.…”

Section: Introductionmentioning

confidence: 99%

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Open‐access high‐resolution mass spectrometry in early drug discovery

Thomas¹,

Gerhard²

2004

J. Mass Spectrom.

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Techniques such as mass spectrometry and NMR spectroscopy form an essential part of the medicinal chemist's toolbox for characterizing and assessing the purity of new molecules. Empowering medicinal chemists to gain early insight into their reaction products has a direct impact on productivity. Devolution of cutting-edge techniques from the specialist to the bench chemist also frees the specialist to concentrate on solving the more demanding of analytical problems. For open-access techniques to be taken up, they must be robust and be able to handle differing sample concentrations and varying sample complexities. This paper details the implementation of high-resolution liquid chromatography/mass spectrometry in open access to aid the medicinal chemist in characterizing desired products and identifying unexpected rearrangements, by-products and complete unknowns.

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Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Open‐access high‐resolution mass spectrometry in early drug discovery

Thomas¹,

Gerhard²

2004

J. Mass Spectrom.

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“…Open access mass spectrometry has been introduced in other laboratories (Brown et al, 1994;Pullen et al, 1995;Taylor et al, 1995;Wood and Hachey, 2000;Mallis et al, 2002;Greaves, 2002). These systems, however, were designed to obtain structural information rather than for quantitative assays.…”

Section: Introductionmentioning

confidence: 96%

Evolution of an open‐access quantitative bioanalytical mass spectrometry service in a drug discovery environment

Wright

Chassaing

Cussans

et al. 2006

Biomedical Chromatography

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Increased demand for assays for compounds at the early stages of drug discovery within the pharmaceutical industry has led to the need for open-access mass spectrometry systems for performing quantitative analysis in a variety of biological matrices. The open-access mass spectrometers described here are LC/MS/MS systems operated in 'multiple reaction monitoring' (MRM) mode to obtain the sensitivity and specificity required to quantitate low levels of pharmaceutical compounds in an excess of biological matrix. Instigation of these open-access systems has resulted in mass spectrometers becoming the detectors of choice for non-expert users, drastically reducing analytical method development time and allowing drug discovery scientists to concentrate on their core expertise of pharmacokinetics and drug metabolism. Setting up an open-access facility that effectively allows a user with minimal mass spectral knowledge to exploit the MS/MS capability of triple quadrupole mass spectrometers presents a significantly different challenge from setting up qualitative single stage mass spectrometry systems. Evolution of quantitative open access mass spectrometry within a pharmaceutical drug metabolism and pharmacokinetics group, from its beginnings as a single generic system to a series of specialist fully integrated walk-up facilities, is described.

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“…Even if we cannot, for example, obtain a mass spectrum on 90 compounds in parallel, we can try to obtain each spectrum automatically and run the spectrometer 24 hours a day. 7,8 However, the tasks of serial purification and quantitation are more complex.…”

mentioning

confidence: 99%

Structure-controlled automated purification of parallel synthesis products in drug discovery

Kiplinger

Cole

Robinson

et al. 1998

Rapid Commun. Mass Spectrom.

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Extensive automation of both random and rational drug discovery strategies greatly increases the number of compounds entering biological screens. Although parallel synthesis (one compound per well) strategies eliminate the deconvolution step necessary when pooled libraries are screened, parallel synthesis products are usually screened as crude mixtures, because purification slows the process of lead discovery. Screening crude products is sometimes complicated by synergies and interferences between compounds. Screening pure compounds is the only sure route to immediate, reliable structure -activity relationships.Automated purification strategies are designed to limit or remove the purification bottleneck between synthesis and screening. In this paper, a workstation is described which uses a combination of UV absorbance and mass spectrometric data to make real-time decisions for HPLC fraction collection, allowing selection of compounds based on mass or substructure. This methodology has demonstrated success with parallel synthesis products in drug discovery applications. #

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Putting mass spectrometry in the hands of the end user

Cited by 44 publications

References 11 publications

Open‐access high‐resolution mass spectrometry in early drug discovery

Open‐access high‐resolution mass spectrometry in early drug discovery

Evolution of an open‐access quantitative bioanalytical mass spectrometry service in a drug discovery environment

Structure-controlled automated purification of parallel synthesis products in drug discovery

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