Assessment and validation of the p-QuEChERS sample preparation methodology for the analysis of >200 veterinary drugs in various animal-based food matrices.

The need remains for veterinary multi-residue methods that reliably quantify and identify veterinary drugs in the various animal-based food matrices. Such a method should not only show good method performance parameters (e.g.

Simplifying Nontargeted Analysis of PFAS in Complex Food Matrixes.

Background: Per- and polyfluoroalkyl substances (PFAS) are a class of toxic environmental contaminants that are characterized by their high chemical stability and enormous structural diversity.

Objective: The limited availability of PFAS reference standards is the main motivation for developing nontargeted analytical methods. Current concepts are complex and rely on multiple filtering steps (e.

Improving the QuEChERS Liquid/Liquid Extraction of Analytes With Widely Varying Physicochemical Properties: Example of 201 Veterinary Drugs in Milk.

Background: QuEChERS is an extraction and sample processing technique widely used for multiresidue methods (e.g., pesticides or veterinary drugs).

High resolution mass spectrometry-based detection and quantification of β-agonists at relevant trace levels in a variety of animal-based food matrices.

β-agonists have been illegally used for growth promoting purposes in animal husbandry, leading to residue concentrations capable of inducing acute toxic reactions among consumers of animal-based food. There is not only a need for detecting β-agonist residues at low concentrations, but also to increase the number of compounds to be monitored. It was therefore the aim of this paper to develop a unified method capable of detecting a wide range of different β-agonists (20 analytes including some metabolites) in a variety of matrices (muscle, liver, plasma, milk and urine).

The use of UHPLC, IMS, and HRMS in multiresidue analytical methods: A critical review.

Residue chemists who analyse pesticides in vegetables or veterinary drugs in animal-based food are currently facing a situation where there is a requirement to detect more and more compounds at lower and lower concentrations. Conventional tandem quadrupole instruments provide sufficient sensitivity, but speed and selectivity appear as future limitations. This will become an even larger issue when there is a need to not only detect active compounds but also their degradation products and metabolites.

High-resolution mass spectrometry for bioanalytical applications: Is this the new gold standard?

Liquid chromatography coupled to quadrupole-based tandem mass spectrometry (QqQ) is termed the "gold standard" for bioanalytical applications because of its unpreceded selectivity, sensitivity, and the ruggedness of the technology. More recently, however, high-resolution mass spectrometry (HRMS) has become increasingly popular for bioanalytical applications. Nonetheless, this technique is still viewed, either as a screening technology or as a research tool.

Partially overlapping sequential window acquisition of all theoretical mass spectra: A methodology to improve the spectra quality of veterinary drugs present at low concentrations in highly complex biological matrices.

Rationale: Residues of veterinary drugs in food matrices have to be detected, identified and confirmed at low concentrations. Data-independent acquisition (DIA) methods such as the sequential window acquisition of all theoretical spectra (SWATH) permit the extraction of relatively clean spectra out of complex matrices. Such spectra can be significantly improved by using a modified SWATH algorithm which provides several times narrower mass isolation windows without affecting the cycle time.

Analytical performance of the various acquisition modes in Orbitrap MS and MS/MS.

Quadrupole Orbitrap instruments (Q Orbitrap) permit high-resolution mass spectrometry-based full scan acquisitions and have a number of acquisition modes where the quadrupole isolates a particular mass range prior to a possible fragmentation and high-resolution mass spectrometry-based acquisition. Selecting the proper acquisition mode(s) is essential if trace analytes are to be quantified in complex matrix extracts. Depending on the particular requirements, such as sensitivity, selectivity of detection, linear dynamic range, and speed of analysis, different acquisition modes may have to be chosen.

Analysis of a variety of inorganic and organic additives in food products by ion-pairing liquid chromatography coupled to high-resolution mass spectrometry.

A reversed-phase ion-pairing chromatographic method was developed for the detection and quantification of inorganic and organic anionic food additives. A single-stage high-resolution mass spectrometer (orbitrap ion trap, Orbitrap) was used to detect the accurate masses of the unfragmented analyte ions. The developed ion-pairing chromatography method was based on a dibutylamine/hexafluoro-2-propanol buffer.

Coalescence and self-bunching observed in commercial high-resolution mass spectrometry instrumentation.

Rationale: Self-bunching and coalescence are well-known effects in Fourier transform ion cyclotron resonance (FTICR) and multi-reflection time-of-flight (TOF) mass spectrometry. These detrimental effects can also be observed in currently more frequently used high-resolution mass spectrometry (HRMS) instruments, such as the Orbitrap and single-reflection TOF.

Methods: A modern single-reflection TOF and a Q-Orbitrap were used to produce conditions in which self-bunching and coalescence were observed.

Easy and Fast Method for the Determination of Biogenic Amines in Fish and Fish Products with Liquid Chromatography Coupled to Orbitrap Tandem Mass Spectrometry.

A quantitative method for the determination of biogenic amines was developed. The method is characterized by the virtual absence of sample cleanup and does not require a derivatization reaction. Diluted extracts are centrifuged, filtrated, and directly injected into an ultra-HPLC column, which is coupled to a single-stage high-resolution mass spectrometer (Orbitrap).

Using In Silico Fragmentation to Improve Routine Residue Screening in Complex Matrices.

Targeted residue screening requires the use of reference substances in order to identify potential residues. This becomes a difficult issue when using multi-residue methods capable of analyzing several hundreds of analytes. Therefore, the capability of in silico fragmentation based on a structure database ("suspect screening") instead of physical reference substances for routine targeted residue screening was investigated.

Comparison of linear intrascan and interscan dynamic ranges of Orbitrap and ion-mobility time-of-flight mass spectrometers.

Rationale: The linear intrascan and interscan dynamic ranges of mass spectrometers are important in metabolome and residue analysis. A large linear dynamic range is mandatory if both low- and high-abundance ions have to be detected and quantitated in heavy matrix samples. These performance criteria, as provided by modern high-resolution mass spectrometry (HRMS), were systematically investigated.

Practical application of in silico fragmentation based residue screening with ion mobility high-resolution mass spectrometry.

Rationale: A screening concept for residues in complex matrices based on liquid chromatography coupled to ion mobility high-resolution mass spectrometry LC/IMS-HRMS is presented. The comprehensive four-dimensional data (chromatographic retention time, drift time, mass-to-charge and ion abundance) obtained in data-independent acquisition (DIA) mode was used for data mining. An in silico fragmenter utilizing a molecular structure database was used for suspect screening, instead of targeted screening with reference substances.

High throughput-screening of animal urine samples: It is fast but is it also reliable?

Advanced analytical technologies like ultra-high-performance liquid chromatography coupled to high resolution mass spectrometry can be used for veterinary drug screening of animal urine. The technique is sufficiently robust and reliable to detect veterinary drugs in urine samples of animals where the maximum residue limit of these compounds in organs like muscle, kidney, or liver has been exceeded. The limitations and possibilities of the technique are discussed.

Nested data independent MS/MS acquisition.

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.

Improved performance of multiplexed targeted tandem mass spectrometry scans using customized Q Orbitrap data acquisition.

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.

Determination of corticosteroids, anabolic steroids, and basic nonsteroidal anti-inflammatory drugs in milk and animal tissues.

A quantitative LC/MS/MS method was developed for the determination of 14 steroidal compounds and three basic nonsteroidal anti-inflammatory drugs (detected as metabolites) in bovine milk and animal muscle tissue. The proposed method is sufficiently sensitive and highly selective for residue applications. The described approach offers the possibility to detect, quantify, and confirm anti-inflammatory drugs belonging to two widely diverging chemical categories.

Signal suppression can bias selected reaction monitoring ratios. Implications for the confirmation of positive findings in residue testing.

Rationale: Selected reaction monitoring (SRM) ratios based on two or more transitions are commonly used to confirm the identity of a suspected finding in residue testing. International norms like the EU directive commission decision 2002/657/EC (CD) require the use of such ratios to prove the unequivocal identification of a particular compound detected at trace level (confirmation of a suspected residue).

Methods: In this study, the relative abundances of different precursor ions (e.

Study of high-resolution mass spectrometry technology as a replacement for tandem mass spectrometry in the field of quantitative pesticide residue analysis.

A validated LC/MS/MS-based multiresidue pesticide method was converted to an LC high-resolution MS single-stage Orbitrap platform. No changes regarding the cleanup and LC were made. Optimization of high-resolution MS-specific parameters and interface settings was kept at a minimum.

The current role of high-resolution mass spectrometry in food analysis.

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.

Quantitative and confirmative performance of liquid chromatography coupled to high-resolution mass spectrometry compared to tandem mass spectrometry.

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.

Semi-targeted residue screening in complex matrices with liquid chromatography coupled to high resolution mass spectrometry: current possibilities and limitations.

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.

Strategy for the elucidation of elemental compositions of trace analytes based on a mass resolution of 100,000 full width at half maximum.

Elemental compositions (ECs) can be elucidated by evaluating the high-resolution mass spectra of unknown or suspected unfragmented analyte ions. Classical approaches utilize the exact mass of the monoisotopic peak (M + 0) and the relative abundance of isotope peaks (M + 1 and M + 2). The availability of high-resolution instruments like the Orbitrap currently permits mass resolutions up to 100,000 full width at half maximum.

False-positive liquid chromatography/tandem mass spectrometric confirmation of sebuthylazine residues using the identification points system according to EU directive 2002/657/EC due to a biogenic insecticide in tarragon.

In pesticide residue analysis using liquid chromatography/tandem mass spectrometry (LC/MS/MS) the confirmation of a sebuthylazine finding in a tarragon (Artemisia dranunculus) sample was demonstrated to be false positive. A coeluting interfering matrix compound produced product ions in MS/MS analysis, perfectly corresponding to the multiple reaction monitoring (MRM) of two sebuthylazine transitions. Using the EU directive 2002/657/EC which regulates the confirmation of suspected positive findings would have resulted in a false-positive finding.