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Kaufmann A.,Kantonales Labor Zurich | Walker S.,Kantonales Labor Zurich
Rapid Communications in Mass Spectrometry | Year: 2016

Rationale The Q Orbitrap permits multiplexed targeted selected ion monitoring (SIM) or tandem mass spectrometry (MS/MS) scans. Such scans provide a significantly higher sensitivity than conventional full scan acquisition. However, due to the multiplexing, a monitored product ion extracted from a MS/MS scan can no longer be linked to the precursor ion from which it was derived. Furthermore, due to the automatic gain control, quantification based on targeted product ions acquired in the multiplexed MS/MS mode can become questionable. Methods The application programming interface (API) of the Q Exactive has been used to program a multiplexed targeted MS/MS mode that permits the establishment of a link (based on digital coding) between the product ion and the responsible precursor ion. Furthermore, switching off the automatic gain control feature and the definition of appropriate C-trap settings were tested to improve the quantification performance. Results The use of dedicated decoding scans permitted the clear assignment of all monitored product ions to the responsible precursor ion. Furthermore, the customized multiplexed targeted scan used for quantification showed good sensitivity and linearity for a maximum number of eight co-eluting analytes. Conclusions Multiplexed targeted MS/MS scans can be optimized to provide better selectivity (correct linking of an observed product ion to the responsible precursor ion) as well as improved quantitative performance (enforcement of an identical ion injection time for all targeted precursor ions). These two improvements are relevant for quantitative residue analysis. Copyright © 2016 John Wiley & Sons, Ltd.


Kaufmann A.,Official Food Control Authority | Kaufmann A.,Kantonales Labor Zurich | Butcher P.,Official Food Control Authority | Maden K.,Official Food Control Authority | And 2 more authors.
Analyst | Year: 2011

Some twenty cultured fish samples were analyzed for possible residues of veterinary drugs with high resolution mass spectrometry (single stage Orbitrap) coupled to ultra performance liquid chromatography. Quantitative analysis based on external standards covered 110 analytes. Some 116 additional compounds were monitored without having access to reference materials. Detection was based on calculated exact masses and narrow mass windows. Furthermore, a number of semi-targeted techniques were evaluated and compared to corresponding triple quadrupole precursor scan experiments. Single stage high resolution mass spectrometry was used to monitor compound specific product ions (without relying on a previous precursor selection). The capabilities of neutral loss searches based on exact masses were shown by detecting small concentrations of incurred oxytetracycline residues. High resolution mass spectrometry provided more sensitivity and selectivity than corresponding tandem quadrupole precursor and neutral loss scans. The currently limiting factor is the not adequate performance of the available software used for data mining. The high number of false positives that were produced, when searching for chlorine isotopic patterns, was clearly linked to the fact that the utilized software does not perform a peak deconvolution, but simply investigates one individual spectrum after another. © 2011 The Royal Society of Chemistry.


Kaufmann A.,Official Food Control Authority | Kaufmann A.,Kantonales Labor Zurich
Analytical and Bioanalytical Chemistry | Year: 2012

High-resolution mass spectrometry (HRMS), which is used for residue analysis in food, has gained wider acceptance in the last few years. This development is due to the availability of more rugged, sensitive, and selective instrumentation. The benefits provided by HRMS over classical unit-mass-resolution tandem mass spectrometry are considerable. These benefits include the collection of full-scan spectra, which provides greater insight into the composition of a sample. Consequently, the analyst has the freedom to measure compounds without previous compound-specific tuning, the possibility of retrospective data analysis, and the capability of performing structural elucidations of unknown or suspected compounds. HRMS strongly competes with classical tandem mass spectrometry in the field of quantitative multiresidue methods (e.g., pesticides and veterinary drugs). It is one of the most promising tools when moving towards nontargeted approaches. Certain hardware and software issues still have to be addressed by the instrument manufacturers for it to dislodge tandem mass spectrometry from its position as the standard trace analysis tool. © Springer-Verlag 2012.


Kaufmann A.,Kantonales Labor Zurich | Walker S.,Kantonales Labor Zurich | Mol G.,Kantonales Labor Zurich
Rapid Communications in Mass Spectrometry | Year: 2016

Rationale Elucidation of the elemental compositions of unknown compounds (e.g., in metabolomics) generally relies on the availability of accurate masses and isotopic ratios. This study focuses on the information provided by the abundance ratio within a product ion pair (monoisotopic versus the first isotopic peak) when isolating and fragmenting the first isotopic ion (first isotopic mass spectrum) of the precursor. Methods This process relies on the capability of the quadrupole within the Q Orbitrap instrument to isolate a very narrow mass window. Selecting only the first isotopic peak (first isotopic mass spectrum) leads to the observation of a unique product ion pair. The lighter ion within such an isotopologue pair is monoisotopic, while the heavier ion contains a single carbon isotope. The observed abundance ratio is governed by the percentage of carbon atoms lost during the fragmentation and can be described by a hypergeometric distribution. Results The observed carbon isotopologue abundance ratio (product ion isotopologue pattern) gives reliable information regarding the percentage of carbon atoms lost in the fragmentation process. It therefore facilitates the elucidation of the involved precursor and product ions. Unlike conventional isotopic abundances, the product ion isotopologue pattern is hardly affected by isobaric interferences. Furthermore, the appearance of these pairs greatly aids in cleaning up a 'matrix-contaminated' product ion spectrum. Conclusions The product ion isotopologue pattern is a valuable tool for structural elucidation. It increases confidence in results and permits structural elucidations for heavier ions. This tool is also very useful in elucidating the elemental composition of product ions. Such information is highly valued in the field of multi-residue analysis, where the accurate mass of product ions is required for the confirmation process. Copyright © 2016 John Wiley & Sons, Ltd.


Kaufmann A.,Kantonales Labor Zurich | Butcher P.,Kantonales Labor Zurich | Maden K.,Kantonales Labor Zurich | Walker S.,Kantonales Labor Zurich | Widmer M.,Kantonales Labor Zurich
Talanta | Year: 2011

A simple method for the determination of some anthelmintic drugs and phenylbutazone residues in milk and muscle was developed. Following a fast and easy extraction and evaporation procedure, the extract was injected into an ultra performance liquid chromatography system coupled to a single stage Orbitrap detector. The high mass resolution of 50,000 full width at half maximum and corresponding narrow mass windows permitted a very selective and sensitive detection of analytes without requiring fragmentation of the observed [M+H] + or [M+Na]+ ions. This eliminated some difficulties which have plagued the analysis of compounds belonging to the group of avermectins. The analytical method was validated according to the EU commission decision for Orbitrap based, but also for more traditional tandem mass spectrometry based detection and quantification. Equal repeatability but significantly higher sensitivity for critical compounds (avermectins) was obtained for the Orbitrap based detection. A result of this study was the conclusion that analytes with poor fragmentation properties (e.g. sodium-cationized molecules) can be more easily quantified by single stage high resolution mass spectrometry than by tandem mass spectrometry. © 2011 Elsevier B.V.


Kaufmann A.,Kantonales Labor Zurich | Walker S.,Kantonales Labor Zurich
Rapid Communications in Mass Spectrometry | Year: 2013

The determination of acceptable mass error tolerances for high-resolution mass spectrometry based signals has been evaluated in a comprehensive way. This was achieved by using a technical approach which is based on the post-column infusion of an analyte containing solution. This well-known experimental setup was not used to spot signal suppression regions of a particular analyte, but to spot regions of the chromatogram where a systematic mass drift of the analyte ion can be observed (isobaric interference plot). Not the changing signal intensity but the stability of the measured analyte mass was observed. A wide range of different analytes in combinations with potentially interfering matrices has been evaluated. Furthermore, different mass resolving power settings were evaluated. Isobaric interferences between matrix compounds and analytes were common at mass resolving powers <50 000 full width at half maximum. The proposed post-column infusion technique is a useful tool for the determination of the assay and matrix-specific mass error tolerances. It aims to ensure the highest possible selectivity, at the same time preventing the encounter of detrimental mass error related peak deformations as well as false negative findings. Unlike conventional matrix spiking approaches, isobaric interference plots provide information of potential interferences across the whole chromatographic time range. This becomes relevant when there is a relative retention time shift between the analyte and potential interfering matrix compounds. Furthermore, the described setup can be used to study how the mass accuracy of any mass spectrometer is affected by a widely varying total ion current. Copyright © 2012 John Wiley & Sons, Ltd.


Kaufmann A.,Kantonales Labor Zurich | Walker S.,Kantonales Labor Zurich
Rapid Communications in Mass Spectrometry | Year: 2012

Orbitrap technology offers a combination of different technical specifications which have not yet been achieved by other high-resolution mass spectrometry instrumentation. This refers to the combination of sensitivity, dynamic range, mass accuracy, resolution and speed. The high stability of the mass axis and the general ease of use made the orbitrap instrumentation attractive for routine laboratories. However, there are circumstances where significantly deviating relative isotopic abundance (RIA) and shifting accurate masses can be observed. RIA becomes biased at low ion counts. Furthermore, two adjacent, only partially resolved near-isobaric ions are detected with a deviating RIA. The presence of a very intensive mass peak does not only induce Fourier transformation related artefacts (side-lobes) but can cause mass shifts of small adjacent near-isobaric mass peaks. These effects are not as drastic as known for Fourier transform ion cyclotron resonance instruments. Still, users trying to identify or quantify trace level compounds should be aware about such limitations in order to avoid possible pitfalls. © 2012 John Wiley & Sons, Ltd.


Kaufmann A.,Official Food Control Authority | Kaufmann A.,Kantonales Labor Zurich | Butcher P.,Official Food Control Authority | Maden K.,Official Food Control Authority | And 2 more authors.
Rapid Communications in Mass Spectrometry | Year: 2011

The quantitative and confirmative performance of two different mass spectrometry (MS) techniques (high-resolution MS and tandem MS) was critically compared. Evaluated was a new extraction and clean-up protocol which was developed to cover more than 100 different veterinary drugs at trace levels in a number of animal tissues and honey matrices. Both detection techniques, high-resolution mass spectrometry (HRMS) (single-stage Orbitrap instrument operated at 50 000 full width at half maximum) and tandem mass spectrometry (MS/MS) (quadrupole technology) were used to validate the method according to the EU Commission Decision 2002/657/EEC. Equal or even a slightly better quantitative performance was observed for the HRMS-based approach. Sensitivity is higher for unit mass resolution MS/MS if only a subset of the 100 compounds has to be monitored. Confirmation of suspected positive findings can be done by evaluating the intensity ratio between different MS/MS transitions, or by accurate mass based product ion traces (no precursor selection applied). MS/MS relies on compound-specific optimized transitions; hence the second, confirmatory transition generally shows relatively high ion abundance (fragmentation efficacy). This is often not the case in single-stage HRMS, since a generic (not compound-optimized) collision energy is applied. Hence, confirmation of analytes present at low levels is superior when performed by MS/MS. Slightly better precision, but poorer accuracy (fortified matrix extracts versus pure standard solution) of ion ratios were observed when comparing data obtained by HRMS versus MS/MS. Copyright © 2011 John Wiley & Sons, Ltd.


Kaufmann A.,Kantonales Labor Zurich | Walker S.,Kantonales Labor Zurich
Analytical and Bioanalytical Chemistry | Year: 2016

Data independent acquisition (DIA) attempts to provide comprehensive MS/MS data while providing a cycle time that is capable of following the elution profile of chromatographic peaks. Currently available MS technology is not yet fully capable of fulfilling these expectations. This paper suggests a new multiplex-based approach to more closely achieve this objective. Customized scans have been programmed for a Q Orbitrap instrument. Multiple nonadjacent mass range segments are sequentially collected (cut out) by the quadrupole. These combined mass ranges undergo fragmentation, and the resulting product ions are analyzed as a whole by the Orbitrap analyzer. The systematical variation of the mass range segments (nested design) permits the mathematical assignment of the observed product ions within a narrow precursor mass range. The proposed approach allows the use of mass windows that are narrower than those in conventional DIA (SWATH). A unique aspect of the proposed approach is the fact that halving the mass window width requires the addition of only a single multiplexed scan. This is different from conventional DIA, which requires the number of mass windows to be doubled in order to achieve the same objective. This paper shows that for a given cycle time, the proposed nested DIA technique produces significantly less chimeric product ion spectra than conventional DIA. However, further improvements from the programming, and most likely the hardware side, are still required in order to achieve the aim of comprehensive MS/MS. [Figure not available: see fulltext.] © 2016, Springer-Verlag Berlin Heidelberg.


PubMed | Kantonales Labor Zurich
Type: Journal Article | Journal: Analytical and bioanalytical chemistry | Year: 2016

Data independent acquisition (DIA) attempts to provide comprehensive MS/MS data while providing a cycle time that is capable of following the elution profile of chromatographic peaks. Currently available MS technology is not yet fully capable of fulfilling these expectations. This paper suggests a new multiplex-based approach to more closely achieve this objective. Customized scans have been programmed for a Q Orbitrap instrument. Multiple nonadjacent mass range segments are sequentially collected (cut out) by the quadrupole. These combined mass ranges undergo fragmentation, and the resulting product ions are analyzed as a whole by the Orbitrap analyzer. The systematical variation of the mass range segments (nested design) permits the mathematical assignment of the observed product ions within a narrow precursor mass range. The proposed approach allows the use of mass windows that are narrower than those in conventional DIA (SWATH). A unique aspect of the proposed approach is the fact that halving the mass window width requires the addition of only a single multiplexed scan. This is different from conventional DIA, which requires the number of mass windows to be doubled in order to achieve the same objective. This paper shows that for a given cycle time, the proposed nested DIA technique produces significantly less chimeric product ion spectra than conventional DIA. However, further improvements from the programming, and most likely the hardware side, are still required in order to achieve the aim of comprehensive MS/MS. Graphical Abstract Schematic of nested design.

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