A fully automated nanoelectrospray tandem mass spectrometric method for analysis of Caco‐2 samples

Pelt, Colleen K. Van; Zhang, Sheng; Fung, Eliza N.; Chu, Inhou; Liu, Tongtong; Li, Cheng; Korfmacher, Walter A.; Henion, Jack D.

doi:10.1002/rcm.1087

Cited by 75 publications

(50 citation statements)

References 10 publications

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“…A potentially interesting alternative to flow injection is the use of microfabricated nanospray emitter arrays that can be interfaced to multiwell plates using a liquid handling robot (e.g., NanoMate by Advion BioSciences Inc., Ithaca, NY, USA). This system uses a few microliters to load nanospray tips and a cycle time of 40 s/sample [11].…”

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confidence: 99%

Rapid and label-free screening of enzyme inhibitors using segmented flow electrospray ionization mass spectrometry

Pei

Kennedy

2010

J. Am. Soc. Mass Spectrom.

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Electrospray ionization mass spectrometry (ESI-MS) is an attractive analytical tool for high-throughput screening because of its rapid scan time and ability to detect compounds without need for labels. Impediments to the use of ESI-MS for screening have been the relatively large sample consumed and slow sample introduction rates associated with commonly used flow injection analysis. We have previously shown that by segmenting nanoliter plugs of sample with air, an array of discrete samples can be delivered to a platinum-coated emitter tip for ESI-MS analysis with throughput as high as 0.8 Hz and carry-over between samples less than 0.1%. This method was applied to screening for inhibitors of acetylcholinesterase as a demonstration of the potential of segmented flow ESI-MS for such applications. Each enzyme assay consumed 10 nL of sample. At 1 L/min infusion rate, 102 samples were analyzed, corresponding to a 0.65 Hz sample analysis rate. Linear quantification of choline was achieved from 200 M to 10 mM using this method and Z= values were over 0.8 for the assay. Detailed pharmacologic dose-response curves of selected inhibitors were also measured in high-throughput fashion to validate the method. (J Am Soc

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confidence: 99%

Rapid and label-free screening of enzyme inhibitors using segmented flow electrospray ionization mass spectrometry

Pei

Kennedy

2010

J. Am. Soc. Mass Spectrom.

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“…A unique feature of the ESI chip is the incorporation of the ESI ground potential into the spray nozzle so that the electric field around the nozzle tip is formed from the potential difference between the conductive silicon substrate and the voltage applied to the fluid via the conductive pipette tip [7][8][9][10][11]. In such a configuration, the distance that defines the electric field is about 1000 times shorter than the one between the nozzle and mass spectrometer.…”

Section: Coupling Of the Fully Automated Chip-based Nanoesi System Tomentioning

confidence: 99%

“…Different configurations such as single and triple quadrupole, TOF, IT, and ultrahigh-resolution Fouriertransform ion cyclotron resonance (FTICR) mass spectrometers were adapted to chip-based ESI and contributed significant benefits for various studies. However, as nicely illustrated already by a number of reviews [8,11,[20][21][22] the general areas of implementation and applications of chip technologies either silicon-based, glass, or polymer microchips have by far been primarily genomics, drug discovery, and proteomics.…”

Section: Introductionmentioning

confidence: 99%

“…These devices are amenable to high-throughput sample delivery to ESI-MS by automated infusion [8,9] and have the potential to completely replace flow-injection analysis assays. Moreover, the technical quality of the nanosprayers obtained by advanced silicon microtechnology is so high, and the experiments so reproducible, that such devices have been found in some instances to give more robust and quantitative analyses than LC-or CE-MS and to be able to suppress the need for separation prior to MS analysis [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Chip electrospray mass spectrometry for carbohydrate analysis

Zamfir¹,

Bîndilă²,

Lion³

et al. 2005

Electrophoresis

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Currently two types of chip systems are used in conjunction with MS: out-of-plane devices, where hundreds of nozzles, nanospray emitters are integrated onto a single silicon substrate from which electrospray is established perpendicular to the substrate, and planar microchips, embedding a microchannel at the end of which electrospray is generated in-plane, on the edge of the microchip. In the last two years, carbohydrate research greatly benefited from the introduction and implementation of the chip-based MS. In two laboratories the advantages of the chip electrospray in terms of ionization efficiency, sensitivity, reproducibility, quality of data in combination with high mass accuracy, and resolution of detection were systematically explored for several carbohydrate classes: O-and N-glycopeptides, oligosaccharides, gangliosides and glycoprotein-derived O-and N-glycans, and glycopeptides. The current state-of-the-art in interfacing the chip electrospray devices to high-performance MS for carbohydrate analysis, and the particular requirements for method optimization in both positive and negative ion modes are reviewed here. The recent applications of these miniaturized devices and their general potential for glycomic-based surveys are highlighted.

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“…Usually a standard curve is generated for each and every analyte to be quantified [6]. Although reference standards may be available for the parent drug, it is very unlikely to have standards for metabolites available in early stage of drug discovery and development thereby making conventional LC-MS/MS based quantitation of metabolites impractical.Nanospray ionization (NSI), introduced by Wilm and Mann in the 1990s [8], has been used to identify proteins [9 -13] and drug metabolites [14], quantify pharmaceutical drugs [15,16], study absorption, distribution, metabolism and excretion (ADME) properties of drugs [17], and employed in various other applications [12, 13, 15, 16, 18 -34]. NSI-MS has the following advantages over conventional flow ESI-MS: (1) higher sensitivity, (2) lower rate of sample consumption, and (3) improved signal-to-noise ratio (S/N).…”

mentioning

confidence: 99%

Response normalized liquid chromatography nanospray ionization mass spectrometry

Ramanathan¹,

Zhong²,

Blumenkrantz³

et al. 2007

J. Am. Soc. Mass Spectrom.

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The widely different LC-MS response observed for many structurally different compounds limits the use of LC-MS in full scan detection mode for quantitative determination of drugs and metabolites without using reference standard. The recently introduced nanospray ionization (NSI) technique shows comparable MS response for some compounds under non-LC-MS conditions. However, in the presence of numerous endogenous compounds commonly associated with biological samples such as urine, plasma, and bile, LC-MS is required to separate, detect, identify, and measure individual analytes. An LC-NSI-MS system was devised and the MS response obtained in this system for a variety of pharmaceutical drugs and their metabolites. The set-up involves two high-performance liquid chromatography (HPLC) systems, a chip-based NSI source and a quadrupole-time-of-flight (Q-TOF) mass spectrometer. Herein this is referred to as the response normalized-liquid chromatography NSI-MS (RNLC-NSI-MS) system. One HPLC unit performs the analytical separation, while the other unit adds solvent post-column with an exact reverse of the mobile phase composition such that the final composition entering the NSI source is isocratic throughout the entire HPLC run . LC-MS/MS techniques for quantitation require reference and internal standard(s), so that LC-MS/MS responses from unknown quantities of relevant drug-related peaks can be related back to responses obtained using known quantities of each analyte. Usually a standard curve is generated for each and every analyte to be quantified [6]. Although reference standards may be available for the parent drug, it is very unlikely to have standards for metabolites available in early stage of drug discovery and development thereby making conventional LC-MS/MS based quantitation of metabolites impractical.Nanospray ionization (NSI), introduced by Wilm and Mann in the 1990s [8], has been used to identify proteins [9 -13] and drug metabolites [14], quantify pharmaceutical drugs [15,16], study absorption, distribution, metabolism and excretion (ADME) properties of drugs [17], and employed in various other applications [12, 13, 15, 16, 18 -34]. NSI-MS has the following advantages over conventional flow ESI-MS: (1) higher sensitivity, (2) lower rate of sample consumption, and (3) improved signal-to-noise ratio (S/N). Although both on-and off-line NSI-MS have been developed, off-line NSI-MS methods have been more frequently used because of the technical difficulties associated with interfacing conventional flow LC systems with NSI and

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A fully automated nanoelectrospray tandem mass spectrometric method for analysis of Caco‐2 samples

Cited by 75 publications

References 10 publications

Rapid and label-free screening of enzyme inhibitors using segmented flow electrospray ionization mass spectrometry

Rapid and label-free screening of enzyme inhibitors using segmented flow electrospray ionization mass spectrometry

Chip electrospray mass spectrometry for carbohydrate analysis

Response normalized liquid chromatography nanospray ionization mass spectrometry

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