Investigation of an LC-MS-MS (QTrap(R)) Method for the Rapid Screening and Identification of Drugs in Postmortem Toxicology Whole Blood Samples

Herrin, George; McCurdy, H. Horton; Wall, William H.

doi:10.1093/jat/29.7.599

Cited by 64 publications

(28 citation statements)

References 8 publications

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“…The detection of APAP in an actual hair specimen obtained from an acute poisoning case revealed that APAP is incorporated into human hair. Recently, liquid chromatography (LC)-MS [12] and LC-MS-MS [13] have gained popularity in drug analyses. However, the GC-MS technique has various advantages over the LC-MS (-MS), because GC-MS instruments are generally much cheaper and are now very common in forensic laboratories.…”

Section: Discussionmentioning

confidence: 99%

GC-MS assay for acetaminophen in human hair segments

et al. 2008

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Section: Discussionmentioning

confidence: 99%

GC-MS assay for acetaminophen in human hair segments

et al. 2008

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“…Although full-scan MS/MS spectra are not acquired in this mode of operation [termed selected reaction monitoring (SRM) and, its extension, multiple reaction monitoring (MRM)], the method provides high selectivity by monitoring chromatographic coelution of multiple transitions for a given peptide. It is important to note that SRM and MRM have already been successfully applied to a variety of biological applications, including quantification of DNA adducts purified from tissue (8) and detection of doping substances in human urine and plasma (9)(10)(11)(12). To date, the use of SRM and MRM in proteomics is less widespread, although MRM has been used to quantify protein expression (13), to find protein biomarkers for disease severity in rheumatoid arthritis (14), and for detection and quantitative analysis of protein phosphorylation (15)(16)(17).…”

mentioning

confidence: 99%

Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks

Wolf-Yadlin

Hautaniemi

Lauffenburger

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

472

434

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Although recent developments in MS have enabled the identification and quantification of hundreds of phosphorylation sites from a given biological sample, phosphoproteome analysis by MS has been plagued by inconsistent reproducibility arising from automated selection of precursor ions for fragmentation, identification, and quantification. To address this challenge, we have developed a new MS-based strategy, based on multiple reaction monitoring of stable isotope-labeled peptides, that enables highly reproducible quantification of hundreds of nodes (phosphorylation sites) within a signaling network and across multiple conditions simultaneously. We have applied this strategy to quantify temporal phosphorylation profiles of 222 tyrosine phosphorylated peptides across seven time points following EGF treatment, including 31 tyrosine phosphorylation sites not previously known to be regulated by EGF stimulation. With this approach, 88% of the signaling nodes were reproducibly quantified in four analyses, as compared with only 34% by typical information-dependent analysis. As a result of the improved reproducibility, full temporal phosphorylation profiles were generated for an additional 104 signaling nodes with the multiple reaction monitoring strategy, an 88% increase in our coverage of the signaling network. This method is broadly applicable to multiple signaling networks and to a variety of samples, including quantitative analysis of signaling networks in clinical samples. Using this approach, it should now be possible to routinely monitor the phosphorylation status of hundreds of nodes across multiple biological conditions. epidermal growth factor receptor ͉ mass spectrometry ͉ signal transduction ͉ tyrosine phosphorylation L igand binding to cell surface receptors activates multiple protein tyrosine phosphorylation-mediated signaling cascades that regulate many cell biological processes, including proliferation, differentiation, migration, and cell death (1-3). To mechanistically define the relationship between signaling networks and downstream biological responses, it is necessary to quantify the dynamics of protein phosphorylation sites across multiple cell states and to correlate this information to quantitative phenotypic measurements. Until recently, antibody-based assays (e.g., FACS, Western blots, tissue microarrays) have been favored for most signaling network studies. These assays provide excellent quantitative information on the phosphorylation status of selected nodes within the network, but require a priori knowledge of the proteins and phosphorylation sites to be studied and are limited by the need to have high-quality, non-cross-reactive antibodies recognizing specific sites within the network. By comparison, analysis of protein phosphorylation by MS provides the capability of identifying novel phosphorylation sites on novel proteins within the network, requires minimal a priori knowledge, and is therefore compatible with both well and poorly characterized signaling networks. Recent developments in M...

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“…Product ion spectra may also provide higher confidence in compound identification than individual precursor-product ion transitions. IDA-based methods are often used to screen for a large number of drugs, especially when compound identification is more important than quantification (12)(13)(14)(15)(16)(17)(18)(19)(20). Although several studies have investigated the performance of high-resolution instruments from which IDA-product ion spectra are obtained (21)(22)(23)(24)(25)(26)(27), to the best of our knowledge, none have compared their performance to that of nominal mass SRM-IDA methods.…”

mentioning

confidence: 99%

Comparison of Information-Dependent Acquisition on a Tandem Quadrupole TOF vs a Triple Quadrupole Linear Ion Trap Mass Spectrometer for Broad-Spectrum Drug Screening

et al. 2015

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BACKGROUND:Liquid chromatography high-resolution mass spectrometry (LC-HRMS) with untargeted data collection is especially attractive for general unknown drug screening owing to its ability to identify unexpected compounds. LC-HRMS offers several advantages over traditional selected reaction monitoring (SRM) techniques and could be an ideal screening platform as long as its analytical performance is comparable to that of SRMbased methods.

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Investigation of an LC-MS-MS (QTrap(R)) Method for the Rapid Screening and Identification of Drugs in Postmortem Toxicology Whole Blood Samples

Cited by 64 publications

References 8 publications

GC-MS assay for acetaminophen in human hair segments

GC-MS assay for acetaminophen in human hair segments

Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks

Comparison of Information-Dependent Acquisition on a Tandem Quadrupole TOF vs a Triple Quadrupole Linear Ion Trap Mass Spectrometer for Broad-Spectrum Drug Screening

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