Ultra-fast quantitation of saquinavir in human plasma by matrix-assisted laser desorption/ionization and selected reaction monitoring mode detection

Wagner, Michel; Varesio, Emmanuel; Hopfgartner, Gérard

doi:10.1016/j.jchromb.2008.07.009

Cited by 44 publications

(52 citation statements)

References 26 publications

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“…Indeed, with lead pencil as matrix to analyze the HIV protease inhibitor saquinavir in MALDI-TOF and MALDI-FTICR experiments, strong signals were found for the sodium and potassium adducts but not for protonated saquinavir (van Kampen, unpublished experiments). Those data contrast sharply with matrices such as 2,5-DHB and CHCA, which yield intense signals for the protonated molecule (Wagner, Varesio, & Hopfgartner, 2008;van Kampen et al, 2009b). Adding either a sodium salt or a potassium salt to the sample enhances analyte cationization and thereby improves the sensitivity (van Kampen, unpublished experiments).…”

Section: Small-molecule Maldimentioning

confidence: 95%

“…Sophisticated spotting devices such as electrospray deposition instruments (Hensel, King, & Owens, 1997;Wei et al, 2004;Wagner, Varesio, & Hopfgartner, 2008) or piezo-electric droplet dispensers (Little et al, 1997;Allmaier, 1998;Onnerfjord et al, 1998) can be used to obtain a highly homogeneous layer of SMALL-MOLECULE MALDI & co-crystallized sample and matrix to thereby improve the precisions compared to dried-droplet sample preparation. These sophisticated spotting devices might be particularly useful when matrices are used that are known for their heterogeneous crystallization behavior such as 2,5-DHB.…”

Section: B Increasing Homogeneous Sample/ Matrix Crystallizationmentioning

confidence: 99%

“…Relatively simple, fast, and easy-to-automate procedures that allow batch preparation of biological samples are needed to truly benefit from the high-throughput measurements of MALDI-MS. Sample-preparation procedures in 96-or 384-well plates are highly suited for MALDI, because these formats are widely used for MALDI target plates and allow a relatively easy spotting of the processed samples with a pipetting robot (Wu et al, 1997;van Kampen et al, 2006;Wagner, Varesio, & Hopfgartner, 2008).…”

Section: Preparation Of Biological Samplesmentioning

confidence: 99%

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Biomedical application of MALDI mass spectrometry for small‐molecule analysis

Kampen

Burgers

Groot

et al. 2010

Mass Spectrometry Reviews

139

102

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Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is an emerging analytical tool for the analysis of molecules with molar masses below 1,000 Da; that is, small molecules. This technique offers rapid analysis, high sensitivity, low sample consumption, a relative high tolerance towards salts and buffers, and the possibility to store sample on the target plate. The successful application of the technique is, however, hampered by low molecular weight (LMW) matrix-derived interference signals and by poor reproducibility of signal intensities during quantitative analyses. In this review, we focus on the biomedical application of MALDI-MS for the analysis of small molecules and discuss its favorable properties and its challenges as well as strategies to improve the performance of the technique. Furthermore, practical aspects and applications are presented.

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Section: Small-molecule Maldimentioning

confidence: 95%

Section: B Increasing Homogeneous Sample/ Matrix Crystallizationmentioning

confidence: 99%

Section: Preparation Of Biological Samplesmentioning

confidence: 99%

See 1 more Smart Citation

Biomedical application of MALDI mass spectrometry for small‐molecule analysis

Kampen

Burgers

Groot

et al. 2010

Mass Spectrometry Reviews

139

102

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“…Wagner and colleagues [36] have also highlighted the potential for high-throughput in their studies. These authors quantified saquinavir in human plasma samples without prior chromatographic separation.…”

Section: Low Molecular Mass Analytesmentioning

confidence: 99%

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Duncan¹,

Röder²,

Hunsucker³

2008

Briefings in Functional Genomics and Proteomics

197

162

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This review summarizes the essential characteristics of matrix-assisted laser desorption/ionization (MALDI) timeof-flight mass spectrometry (TOF MS), especially as they relate to its applications in quantitative analysis. Approaches to quantification by MALDI-TOF MS are presented and published applications are critically reviewed.Keywords: quantification; quantitative analysis; MALDI; mass spectrometry; biomarkers OVERVIEWSince its inception in 1987 [1], matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF MS) has been applied for the analysis of a wide range of biomolecules. Initial applications were almost exclusively for the qualitative analysis of biopolymers because MALDI-TOF MS provided a fast and accurate approach to molecular mass and purity information: Is my material the right mass and is it free from contaminants? Because of the speed of analysis, ease of use, relative low equipment cost, ease of data interpretation and limited potential for cross-contamination between samples/users, MALDI-TOF MS systems were considered walk-up instruments where investigators run their own samples and determine, within minutes, whether they were on the right track with their work.There were, however, two specific areas of application where MALDI-TOF MS was initially viewed as impractical: i.e. the analysis of low mass analytes and quantitative applications. Low mass analysis is complicated by the vast molar excess of the matrix that can swamp any analyte-specific signal in the low m/z region of the spectrum. Quantitative analysis was viewed as implausible because crystallization does not yield a uniform distribution of the analyte and matrix across the target surface and this gives rise to regions where the analyte signal is especially intense relative to other locations on the target surface. MALDI MS was therefore viewed as inherently irreproducible because, for a given amount of analyte loaded onto the target, the measured ion intensity varies.Subsequently, it has been shown that both these perceived limitations can be overcome and quantification can be routine, both for low and high mass analytes. Now, an extensive list of published applications includes quantification of amino acids, lipids, natural products, drugs, polymers, herbicides, metabolites, toxins, oligonucleotides, carbohydrates, peptides and proteins. (Selected applications from these areas are discussed at the end of this review.) Here, we focus on the quantitative applications of MALDI and illustrate applications relating to both low and high-molecular mass analytes. We also discuss the strategies for applying MALDI to relative and absolute quantification. While MALDI is most commonly combined with TOF analysers, other analyser options are possible and applications employing these are also presented. Our aim is not to provide an exhaustive catalogue of published applications, but to discuss the general principles and to illustrate the

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“…Drug analyses are performed using MS/MS to monitor the drug itself using structure-specific fragments, increasing the sensitivity and providing identification with high confidence. To accomplish the analysis in a high-throughput manner, single or multiple reaction monitoring can be utilized to monitor the structure-related composition of the drug (precursor or parent ion) in the mass spectrometer to form one (single reaction monitoring) or multiple (multiple reaction monitoring) specific fragment ions (50,51). Compared with whole body autoradioluminography, a traditional method to study the spatial distribution of drug candidates in tissue, MALDI-IMS has two advantages: it does not require radiolabeling of the drug of interest and can distinguish between the parent drug and its metabolites (49,52,53).…”

Section: Drug Analysismentioning

confidence: 99%

Imaging of Intact Tissue Sections: Moving beyond the Microscope

Seeley¹,

Schwamborn²,

Caprioli

2011

Journal of Biological Chemistry

106

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MALDI-imaging MS is a new molecular imaging technologyfor direct in situ analysis of thin tissue sections. Multiple analytes can be monitored simultaneously without prior knowledge of their identities and without the need for target-specific reagents such as antibodies. Imaging MS provides important insights into biological processes because the native distributions of molecules are minimally disturbed, and histological features remain intact throughout the analysis. A wide variety of molecules can be imaged, including proteins, peptides, lipids, drugs, and metabolites. Several specific examples are presented to highlight the utility of the technology. MALDI imaging MS (IMS)4 is an emerging new tool for the analysis of biological and clinical tissue samples. It has been shown to be amenable for the analysis of proteins, peptides (both endogenous and enzymatically produced), lipids, and small molecules (such as drugs and endogenous metabolites). Spatial relationships of molecules within a specimen are preserved because intact tissue is directly analyzed without homogenization. In this way, molecules can be interrogated in their native environments, providing new insights into the biological processes involved.IMS requires minimal sample preparation for analysis. Thin sections of tissue samples (typically, 5-10 m thick) are obtained from frozen or formalin-fixed paraffin-embedded (FFPE) tissue blocks and collected on conductive MALDI targets. A matrix compound (typically, a small organic acid as well as a proteolytic enzyme when necessary) is applied to the surface of the tissue sample. Mass spectra are subsequently collected by firing a laser in an ordered pattern of thousands of ablated spots on the tissue section, and a discrete spectrum is collected from each location on the sample. Each ablated spot is analogous to a pixel in a digital photograph. Each pixel (spectrum) contains many analytes that can be individually displayed as a function of their position and relative intensity within the tissue section. In this way, hundreds of images from specific molecular species can be generated simultaneously from a single tissue section without prior knowledge of their identities. Specific reagents such as antibodies are not needed. Alternatively, IMS can be carried out in a profiling mode in which only relatively small selected areas from each tissue section are targeted for analysis. A stained serial section is typically used to guide the analysis. The sample preparation and analysis process of fresh-frozen and FFPE tissues are summarized in Fig. 1.IMS can be very high-throughput in nature. Often, 10 -20 tissue sections can be collected on a single target plate and analyzed concurrently. With currently available high repetition rate lasers (1 kHz or greater), the entire target plate can be analyzed in a matter of a few minutes to a few hours, depending on the desired spatial resolution. It has recently been shown that, through the use of a 5 kHz laser and continuous laser raster, a rat brain measuring 185 mm 2 can ...

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Ultra-fast quantitation of saquinavir in human plasma by matrix-assisted laser desorption/ionization and selected reaction monitoring mode detection

Cited by 44 publications

References 26 publications

Biomedical application of MALDI mass spectrometry for small‐molecule analysis

Biomedical application of MALDI mass spectrometry for small‐molecule analysis

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Imaging of Intact Tissue Sections: Moving beyond the Microscope

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