Anneli Kruve

• Professor
• Professor (Associate) at Stockholm University

Nontarget screening (NTS) with liquid chromatography high-resolution mass spectrometry (LC-HRMS) is commonly used to detect unknown organic micropollutants in the environment. One of the main challenges in NTS is the prioritization of relevant LC-HRMS features. A novel prioritization strategy based on structural alerts to select NTS features that c...

Non-targeted analysis (NTA) is commonly used for the detection and identification of emerging pollutants, including many per- and polyfluoroalkyl substances (PFAS). While NTA outputs are often non-quantitative, concentration estimation is now possible using quantitative non-targeted analysis (qNTA) approaches. To date, few studies have examined mat...

Nontargeted screening (NTS) utilizing liquid chromatography electrospray ionization high-resolution mass spectrometry (LC/ESI/HRMS) is increasingly used to identify environmental contaminants. Major differences in the ionization efficiency of compounds in ESI/HRMS result in widely varying responses and complicate quantitative analysis. Despite an i...

The machine-learning tool MS2Tox can prioritize hazardous nontargeted molecular features in environmental waters, by predicting acute fish lethality of unknown molecules based on their MS² spectra, prior to structural annotation. It has yet to be investigated how the extent of molecular coverage, MS² spectra quality, and toxicity prediction confide...

Recycled textiles are becoming widely available to consumers as manufacturers adopt circular economy principles to reduce the negative impact of garment production. Still, the quality of the source material directly impacts the final product, where the presence of harmful chemicals is of utmost concern. Here, we develop a risk-based suspect and non...

Non-targeted screening with liquid chromatography coupled to high-resolution mass spectrometry (LC/HRMS) is increasingly leveraging in silico methods, including machine learning, to obtain candidate structures for structural annotation of LC/HRMS features and their further prioritization. Candidate structures are commonly retrieved based on the ta...

Nontargeted LC/ESI/HRMS aims to detect and identify organic compounds present in the environment without prior knowledge; however, in practice no LC/ESI/HRMS method is capable of detecting all chemicals, and the scope depends on the instrumental conditions. Different experimental conditions, instruments, and methods used for sample preparation and...

Identification of stereo- and positional isomers detected with high-resolution mass spectrometry (HRMS) is often challenging due to near-identical fragmentation spectra (MS²), similar retention times, and collision cross-section values (CCS). Here we address this challenge on the example of hydroxylated polychlorinated biphenyls (OH-PCBs) with the...

The majority of chemicals detected via nontarget liquid chromatography high-resolution mass spectrometry (HRMS) in environmental samples remain unidentified, challenging the capability of existing machine learning models to pinpoint potential endocrine disruptors (EDs). Here, we predict the activity of unidentified chemicals across 12 bioassays rel...

Recent advances in high-resolution mass spectrometry (HRMS) have enabled the detection of thousands of chemicals from a single sample, while computational methods have improved the identification and quantification of these chemicals in the absence of reference standards typically required in targeted analysis. However, to determine the presence of...

High-resolution mass spectrometry (HRMS)-based suspect and nontarget screening has identified a growing number of novel per- and polyfluoroalkyl substances (PFASs) in the environment. However, without analytical standards, the fraction of overall PFAS exposure accounted for by these suspects remains ambiguous. Fortunately, recent developments in io...

Increasing production and use of chemicals and awareness of their impact on ecosystems and humans has led to large interest for broadening the knowledge on the chemical status of the environment and human health by suspect and non-target screening (NTS). To facilitate effective implementation of NTS in scientific, commercial and governmental labora...

Nontarget analysis by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is now widely used to detect pollutants in the environment. Shifting away from targeted methods has led to detection of previously unseen chemicals, and assessing the risk posed by these newly detected chemicals is an important challenge. Assessing exposure and...

Non-target screening with LC/IMS/HRMS is increasingly employed for detecting and identifying the structure of potentially hazardous chemicals in the environment and food. Structural assignment relies on a combination of multidimensional instrumental methods and computational methods. The candidate structures are often isomeric, and unfortunately, a...

Supercritical fluid chromatography (SFC) is a promising, sustainable, and complementary alternative to liquid chromatography (LC) and has often been coupled with high resolution mass spectrometry (HRMS) for nontarget screening (NTS). Recent developments in predicting the ionization efficiency for LC/ESI/HRMS have enabled quantification of chemicals...

Systematic selection of mobile phase and column chemistry type can be critical for achieving optimal chromatographic separation, high sensitivity, and low detection limits in liquid chromatography electrospray high resolution mass spectrometry (LC/MS). However, the selection process is challenging for non-targeted screening where the compounds of i...

To achieve water quality objectives of the zero pollution action plan in Europe, rapid methods are needed to identify the presence of toxic substances in complex water samples. However, only a small fraction of chemicals detected with nontarget high-resolution mass spectrometry can be identified, and fewer have ecotoxicological data available. We h...

Lower chlorinated polychlorinated biphenyls (LC-PCBs) and their metabolites make up a class of environmental pollutants implicated in a range of adverse outcomes in humans; however, the metabolism of LC-PCBs in human models has received little attention. Here we characterize the metabolism of PCB 2 (3-chlorobiphenyl), an environmentally relevant LC...

The structural annotation of isomeric metabolites remains a key challenge in untargeted electrospray ionization/high-resolution mass spectrometry (ESI/HRMS) metabolomic analysis. Many metabolites are polyfunctional compounds that may form protomers in electrospray ionization sources and therefore yield multiple peaks in ion mobility spectra. Protom...

Non-targeted analysis (NTA) methods are widely used for chemical discovery but seldom employed for quantitation due to a lack of robust methods to estimate chemical concentrations with confidence limits. Herein, we present and evaluate new statistical methods for quantitative NTA (qNTA) using high-resolution mass spectrometry (HRMS) data from EPA’s...

Hydroxylated PCBs are an important class of metabolites of the widely distributed environmental contaminants polychlorinated biphenyls (PCBs). However, the absence of authentic standards is often a limitation when subject to detection, identification, and quantification. Recently, new strategies to quantify compounds detected with non-targeted LC/E...

LC/ESI/HRMS is increasingly employed for monitoring chemical pollutants in water samples, with non-targeted analysis becoming more common. Unfortunately, due to the lack of analytical standards, non-targeted analysis is mostly qualitative. To remedy this, models have been developed to evaluate the response of compounds from their structure, which c...

Structural elucidation of compounds detected with liquid chromatography coupled to high resolution mass spectrometry is a challenging and time-consuming step in the workflow of non-targeted analysis and often requires manual validation of the results. Retention time, alongside exact mass, isotope pattern, fragmentation spectra, and collision cross-...

Non-targeted screening with LC/ESI/HRMS aims to identify the structure of the detected compounds using their retention time, exact mass, and fragmentation pattern. Challenges remain in differentiating between isomeric compounds. One untapped possibility to facilitate identification of isomers relies on different ionic species formed in electrospray...

Rationale: The first comprehensive quantitative scale of the efficiency of electrospray ionization (ESI) in the positive mode by monoprotonation, containing 62 compounds, was published in 2010. Several trends were found between the compound structure and IE but, possibly because of the limited diversity of the compounds, some questions remained. T...

Surface waters are widely used as source for drinking water production and hence their quality needs to be continuously monitored. However, current routine monitoring programs are not comprehensive as they mostly cover only a limited number of known pollutants and emerging contaminants. This study presents a risk-based approach combining suspect an...

Non-targeted screening (NTS) with reversed phase liquid chromatography electrospray ionization high resolution mass spectrometry (LC/ESI/HRMS) is increasingly employed as an alternative to targeted analysis; however, it is not possible to quantify all compounds found in a sample with analytical standards. As an alternative, semi-quantification stra...

A wide range of micropollutants can be monitored with non-targeted screening; however, the quantification of the newly discovered compounds is challenging. Transformation products (TPs) are especially problematic because analytical standards are rarely available. Here, we compared three quantification approaches for non-target compounds that do not...

The variation of ionization efficiency for different compounds has puzzled researchers since the invention of the electrospray mass spectrometry (ESI/MS). Ionization depends on the properties of the compound, eluent, matrix, and instrument. Despite significant research, some aspects have remained unclear. For example, research groups have reached c...

The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innovation programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemical risk assessors and managers together with scientists to accelerate method development and the production of necessar...

Non-targeted and suspect analyses with liquid chromatography/electrospray/high-resolution mass spectrometry (LC/ESI/HRMS) are gaining importance as they enable identification of hundreds or even thousands of compounds in a single sample. Here, we present an approach to address the challenge to quantify compounds identified from LC/HRMS data without...

About ten years ago most of the liquid chromatography (LC) electrospray (ESI) mass spectrometry (MS) analysis of environmental, metabolomics, pharmaceutical samples were predominantly carried out as targeted analysis. Targeted analyses allow detection and quantification a few selected analytes with the aid of standard substances. Today, the centre...

Quantification of analysis results for the suspect and non-targeted screening is essential for obtaining meaningful insight from the measurements. Ionization efficiency predictions is a possible approach to enable quantitation without standard substances. This is, however, especially challenging for the analysis carried out by combining the full sc...

LC/ESI/MS is the technique of choice for qualitative and quantitative food monitoring; however, analysis of a large number of compounds is challenged by the availability of standard substances. The impediment of detection of food contaminants has been overcome by the suspect and non-targeted screening. Still, the results from one laboratory cannot...

Pyridine[4]arenes have previously been considered as anion binding hosts due to the electron-poor nature of the pyridine ring. Herein, we demonstrate the encapsulation of Me4N+ cations inside a dimeric hydrogen-bonded pyridine[4]arene capsule, which contradicts with earlier assumptions. The complexation of a cationic guest inside the pyridine[4]are...

Various dyes present in historical objects can be indicative of different usage, age and origin of the artifacts. Knowledge about the composition and origin of textile dyes is essential for the preservation and conservation of the items. In this paper, we compare different instrumental techniques to detect and identify natural red dyes from histori...

RATIONALE: Choice of mobile phase components and optimal ion source, mainly electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI), are crucial parts in LC/MS method development to achieve higher sensitivity and lower detection limits. In this paper we demonstrate how to rigorously solve these questions by using ionization...

A rapid screening method based on traveling‐wave ion‐mobility spectrometry (TWIMS) combined with tandem mass spectrometry provides insight into the topology of interlocked and knotted molecules, even when they exist in complex mixtures, such as interconverting dynamic combinatorial libraries. A TWIMS characterization of structure‐indicative fragmen...

A rapid screening method based on traveling‐wave ion mobility spectrometry (TWIMS) combined with tandem mass spectrometry provides insight into the topology of interlocked and knotted molecules, even when they exist in complex mixtures such as interconverting dynamic combinatorial libraries. A TWIMS characterization of structure‐indicative fragment...

Choosing an appropriate ion source is a crucial step in liquid chromatography mass spectrometry (LC/MS) method development. In this paper, we compare four ion sources for LC/MS analysis of 40 pesticides in tomato and garlic matrices. We compare electrospray ionisation (ESI) source, thermally focused/heated electrospray (HESI), atmospheric pressure...

Electrospray ionization is widely used to generate gas phase ions from a variety of molecules ranging from small ions to large proteins, while the ionization mechanism is claimed to depend on the size of the molecule. For small molecules, the ionization efficiency, the amount of gas phase ions produced in the electrospray process, depends on the pr...

This poster is about how to modify the acidity of water and methanol droplets with the help of additives and bulk-phase pH.

Ionization efficiencies are studied in complicated biological matrices (plasma, blood, urine, cerebrospinal fluid, brain tissue homogenate, liver tissue homogenate and neat solvent to comapre with). The correlations between measured ionization efficiencies in neat solvent and matrices are high. We developed ionization efficiency prediction models i...

Combining high‐resolution mass spectrometry (HRMS) with liquid chromatography (LC) has considerably increased the capability of analytical chemistry. Among others, it has stimulated the growth of the non‐target analysis, which aims at identifying compounds without their preceding selection. This approach is already widely applied in various fields,...

The importance of metabolites is assessed based on their abundance. Most of the metabolites are at present identified based on ESI/MS measurements and the relative abundance is assessed from the relative peak areas of these metabolites. Unfortunately, relative intensities can be highly misleading as different compounds ionise with vastly different...

Neonicotinoids, including imidacloprid, are extensively used for plant protection against insects. Unfortunately, these effective pesticides are one of the reasons for the decline of the bee population in recent decades. Ensuring application of minimal pesticide quantity and preventing excess requires a fast method for monitoring the coverage on pl...

The concept of acidity in confined spaces is up to date poorly understood; especially, in case of media violating electroneutrality. Here, we describe the acidity of charged droplets via their ability to protonate simple nitrogen bases and we propose ways to modify the protonation efficiency with the help of additives. We observed that the protonat...

We report the efficient condensation of imine-based macrocycles from dialdehyde A and aliphatic diamines B n in pure water. Within the libraries, we identified a family of homologous amphiphilic [2]catenanes, whose self-assembly is primarily driven by the hydrophobic effect. The length and odd-even character of the diamine alkyl linker dictate bot...

Ionization efficiency and mechanism in ESI is strongly affected by the properties of mobile phase. The use of mobile-phase properties to accurately describe droplets in ESI source is convenient but may be inadequate as the composition of the droplets is changing in the plume due to electrochemical reactions occurring in the needle tip as well as co...

This work presents for the first time directly comparable acidities (unified pH, pHabs) of liquid chromatography mobile phases prepared in different solvents. The ionization behaviour of bases in the mobile phases is better described with the unified pH values (as compared to the usually used pH values of the aqueous component of the mobile phase)...

For the first time, the electrospray ionization efficiency (IE) scales in positive and negative mode are united into a single system enabling direct comparison of IE values across ionization modes. This is made possible by the use of a reference compound that ionizes to a similar extent in both positive and negative modes. Thus, choosing the optima...

For the first time the electrospray ionization efficiency (IE) scales in positive and negative mode are united into a single system enabling direct comparison of IE values across ionization modes. This is made possible by the use of a reference compound that ionizes to a similar extent in both positive and negative modes. Thus, choosing the optimal...

LC/ESI/MS is a technique widely used for qualitative and quantitative analysis in various fields. However, quantification is currently possible only for compounds for which the standard substances are available, as the ionization efficiency of different compounds in ESI source differs by orders of magnitude. In this paper we present an approach for...

In this paper, we investigate the sample preparation and analysis process in order to achieve adequate results for surface water collected from rivers that flow through swamps and are consequently rich in organic matter. We show that matrix effects in glyphosate determination can be reduced by optimizing sample volume, liquid chromatography (LC) mo...

Adduct formation is a common ionization method in electrospray ionization mass spectrometry (ESI/MS). However, this process is poorly understood and complicated to control. We demonstrate possibilities to control adduct formation via mobile phase additives in ESI positive mode for 17 oxygen and nitrogen bases. Mobile phase additives were found to b...

Potassium iodide catalysis was applied for the synthesis of protected benzylhydrazines and hydrazinoacetic acid esters by the alkylation of protected hydrazines. Benzylic halogenides and halogenoacetic acid esters were employed as alkylating agents. In these syntheses the reactive alkyl iodide molecules were generated in situ from less reactive hal...

Electrospray ionization efficiency is known to be affected by mobile phase composition. In this paper, a detailed study of analyte ionization efficiency dependence on mobile phase pH is presented. The pH effect was studied on 28 compounds with different chemical properties. Neither pKa nor solution phase ionization degree by itself was observed to...

In part II of this tutorial, the investigated approaches of estimating the limit of detection (LOD) are applied to experimental data from LC-MS measurements. Important practical aspects specific to LC-MS and related to LOD are reviewed. The results of different tests of estimating linearity and scedasticity are compared. LOD estimates obtained with...

A large body of literature exists on the limit of detection (LOD), but there is still a lot of confusion about this important validation parameter. This confusion mainly stems from its statistically complex background. The goal of this two-part tutorial is to discuss and clarify the topic of LOD for practitioners. The two main conclusions of this t...

For the first time, the effect of aqueous phase pH on ionization efficiency was studied in detail using 28 compounds with pKa values from -4 to 8.5. The mobile phase pH was varied from 2.1 to 7.0. It was observed that neither the pKa nor the measured change in the degree of ionization in the mobile phase (also containing organic solvent) explains t...

Electrospray ionization (ESI) efficiency is known to be affected by the properties of the analytes, source design and source parameters. In this study, the ionization efficiency of 17 acidic compounds at various conditions in ESI negative ion mode was evaluated. Namely, the influence of organic solvent content in the mobile phase, ionization source...

The aim of the study was to provide a comprehensive overview of neonicotinoid pesticide residues in honey samples for a single country and compare the results with the import data for neonicotinoid pesticides. The levels of four neonicotinoid pesticides, namely thiamethoxam, imidacloprid, acetamiprid, and thiacloprid, were determined in 294 honey s...

The ability of polyprotic acids to give doubly charged ions in negative mode electrospray was studied and related to physicochemical properties of the acids via linear discriminant analysis (LDA). It was discovered that the compound has to be strongly acidic (low pKa1 and pKa2) and to have high hydrophobicity (logPow) to become multiply charged. Ab...

Recent evidence has shown that the atmospheric pressure chemical ionization (APCI) mechanism can be more complex than generally assumed. In order to better understand the processes in the APCI source, for the first time an ionization efficiency scale for APCI source has been created. The scale spans over 5 logIE units and includes 40 compounds with...

For the first time, quantitative electrospray (ESI) ionization efficiencies (IE), expressed as logIE values, obtained on different mass-spectrometric setups (four mass analyzers and four ESI sources) are compared for 15 compounds of diverse properties. The general trends of change of IE with molecular structure are the same with all experimental se...

New faster and simpler methods for determination of pesticides in agricultural products are necessary as requirements for food safety are becoming increasingly stringent. One possibility is to introduce a fast, easy and low-cost screening method before liquid chromatography mass spectrometry analyses. We hereby present a systematic proof of concept...

This work introduces a conceptually new approach of measuring pH of mixed-solvent liquid chromatography (LC) mobile phases. Mobile phase pH is very important in LC, but its correct measurement is not straightforward and all commonly used approaches have deficiencies. The new approach is based on the recently introduced unified pH (pHabs) scale, whi...

Electrospray (ESI) ionization efficiencies (IE) of a set of 10 compounds differing by chemical nature, extent of ionization in solution (basicity), and by hydrophobicity (tetrapropylammonium and tetraethylammonium ion, triethylamine, 1-naphthylamine, N,N-dimethylaniline, diphenylphthalate, dimethylphtahalate, piperidine, pyrrolidine, pyridine) have...

Electrospray ionization (ESI) in the negative ion mode has received less attention in fundamental studies than the positive ion electrospray ionization. In this paper we study the efficiency of negative ion formation in ESI source via deprotonation of substituted phenols and benzoic acids and explore correlations of the obtained ionization efficien...

Two different methods to reinforce the poly(glycidyl methacrylate-co-ethylene dimethacrylate) HPLC monolithic columns of 3 mm id in a glass column reservoir were studied: composite columns with polymeric particles in the monolith and surface treatment of reservoir wall. Out of the two methods used to counter the mechanical instability and formation...

Formation of sodium adducts in electrospray (ESI) has been known for long time, but has not been used extensively in practice, and several important aspects of Na(+) adduct formation in ESI source have been almost unexplored: the ionization efficiency of different molecules via Na(+) adduct formation, its dependence on molecular structure and Na(+)...

In this paper some of the most common methods for overcoming matrix effects in LC/ESI/MS (matrix-matched calibration, standard addition, post-column standard infusion, extrapolative dilution, and post-column flow splitting) are compared according to their ability to give both true and accurate results for pesticide determination in complicated matr...

A novel electrospray nebulizer has been designed, which includes an additional nebulization gas capillary inside the liquid capillary. This design offers significantly enhanced ionization efficiency compared with the classic nebulizer design and leads to improved sensitivity (by three to 10 times) and decreases the detection limit, on an average 10...

Glyphosate is one of the most common pesticides used in the pre-harvest treatment of cereals. This paper examines the matrix effect of glyphosate liquid chromatography/electrospray ionization mass spectrometric (LC/ESI-MS) analysis in wheat and rye. The matrix effect (ionization suppression) was found to be dependent on sample particle size taken f...

Matrix effect (ME) - ionisation suppression or enhancement - in liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) is caused by matrix components co-eluting with the analytes. ME has a complex and not fully understood nature. ME is also highly variable from sample to sample making it difficult to compensate for. In this wor...

Optimization of both the ionization process and ion transportation in the mass spectrometer is of crucial importance in order to achieve high sensitivity and low detection limits and acceptable accuracy in liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) analysis. In this paper four optimization procedures of electrospray...

Nine European universities have formed a consortium that offers a jointly delivered Master's degree program called Measurement Science in Chemistry (MSC) for people educated in analytical chemical measurements. The intention of the consortium is to offer master-level education in analytical chemistry adapted to job market requirements for analytica...

Ionization efficiency (IE) of different compounds in electrospray ionization (ESI) source differs widely, leading to widely differing sensitivities of ESI-MS to different analytes. An approach for quantifying ESI efficiencies (as logIE values) and setting up a self-consistent quantitative experimental ESI efficiency scale of organic compounds under...

The matrix effects in HPLC/electrospray ionization (ESI)-MS analysis are difficult to compensate for because of their large variability. It is, therefore, often more practical to include uncertainty due to the matrix effect into the uncertainty budget rather than try to compensate. This work presents an empirical approach--the matrix effect graph a...

Liquid chromatography electrospray mass spectrometry--LC/ESI/MS--a primary tool for analysis of low volatility compounds in difficult matrices--suffers from the matrix effects in the ESI ionization. It is well known that matrix effects can be reduced by sample dilution. However, the efficiency of simple sample dilution is often limited, in particul...

Three sample preparation methods: Luke method (AOAC 985.22), QuEChERS (quick, easy, cheap, effective, rugged and safe) and matrix solid-phase dispersion (MSPD) were applied to different fruits and vegetables for analysis of 14 pesticide residues by high-performance liquid chromatography with electrospray ionization-mass spectrometry (HPLC/ESI/MS)....

An approach that allows setting up under predefined ionization conditions a rugged self-consistent quantitative experimental scale of electrospray ionization (ESI) efficiencies of organic compounds is presented. By ESI ionization efficiency (IE) we mean the efficiency of generating gas-phase ions from analyte molecules or ions in the ESI source. Th...

Pesticides, which are widely used in agriculture to increase production or protect crop, are known to be potentially dangerous to consumers. Therefore oranges from local supermarket were analysed by the LC–ESI–MS method to determine the presence of pesticides. Two pesticides – thiabendazole and imazalil – were found in the oranges. Both are post-ha...