Publications by authors named "Peter J Schoenmakers"

120 Publications

Spotting isomer mixtures in forensic illicit drug casework with GC-VUV using automated coelution detection and spectral deconvolution.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Mar 29;1173:122675. Epub 2021 Mar 29.

Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, PO Box 94157, Amsterdam 1090 GD, the Netherlands; Co van Ledden Hulsebosch Center (CLHC), Amsterdam Center for Forensic Science and Medicine, PO Box 94157, Amsterdam 1090 GD, the Netherlands.

Analysis of isomeric mixtures is a significant analytical challenge. In the forensic field, for example, over 1000 new psychoactive substances (NPSs), comprising of many closely related and often isomeric varieties, entered the drugs-of-abuse market within the last decade. Unambiguous identification of the isomeric form requires advanced spectroscopic techniques, such as GC-Vacuum Ultraviolet Spectroscopy (GC-VUV). The continuous development of NPSs makes the appearance of a novel compound in case samples a realistic scenario. While several analytical solutions have been presented recently to confidently distinguish NPS isomers, the presence of multiple isomers in a single drug sample is typically not considered. Due to their structural similarities it is possible that a novel NPS coelutes with a known isomer and thus remains undetected. This study investigates the capabilities of VUV spectral deconvolution for peak detection and identification in incompletely resolved drug mixtures. To mimic worst case scenarios, severe coelution was deliberately induced at elevated GC temperatures. The deconvolution software was nevertheless able to correctly detect both substances, even in case of near-identical VUV spectra at almost full coelution. As a next step, spectra were subsequently removed from the reference library to simulate the scenario in which a novel substance was encountered for the first time in forensic case work. However, also in this situation the deconvolution software still detected the coelution. This work shows that a VUV library match score below 0.998 may serve as a warning that a novel substance may be present in a street sample.
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http://dx.doi.org/10.1016/j.jchromb.2021.122675DOI Listing
March 2021

Charge-Based Separation of Acid-Functional Polymers by Non-aqueous Capillary Electrophoresis Employing Deprotonation and Heteroconjugation Approaches.

Anal Chem 2021 04 1;93(14):5924-5930. Epub 2021 Apr 1.

Analytical Technology Centre, DSM Coating Resins, Sluisweg 12, 5145PE Waalwijk, The Netherlands.

Water-borne polymers are in ever-increasing demand due to their favorable ecological profile compared to traditional solvent-borne polymer systems. Many water-borne polymer particles are stabilized in aqueous media by the incorporation of acid-functional monomers. Due to the large variety of comonomers applied, these water-borne polymers have various superimposed statistical distributions, which make it challenging to obtain in-depth information regarding incorporation of the acidic monomers. For selective analysis of the incorporated acidic monomers, a charge-based non-aqueous capillary electrophoresis (NACE) separation was developed. Two approaches were developed: (i) deprotonation of the acid functionality with an organically soluble strong base and (ii) heteroconjugation of anions of carboxylic acids with incorporated acid functionality. In both approaches, -methylpyrrolidone, as a strong solvent for polymers with a favorable relative permittivity for the presence of dissociated ionic species, was used for the separation. It was shown that anions of carboxylic acids specifically associate with the incorporated acid groups in the polymers, resulting in negatively charged complexes that could be separated based on charge-to-size ratio by NACE. Although both approaches give comparable results with respect to acid distribution for acid-functional polymers, the effective mobility of the deprotonated polymers is roughly double that obtained from the heteroconjugation approach. Unlike the heteroconjugation approach, deprotonation conditions were detrimental to the fused-silica capillary, limiting practical use. Polymers with different chemical compositions, molecular weights, and acid contents were subjected to the CE approaches developed. Polymers with varying molecular weight but similar relative acid monomer content were shown to have similar migration times, which confirms that this approach separates polymers based on charge-to-size ratio.
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http://dx.doi.org/10.1021/acs.analchem.1c00311DOI Listing
April 2021

Development of comprehensive two-dimensional low-flow liquid-chromatography setup coupled to high-resolution mass spectrometry for shotgun proteomics.

Anal Chim Acta 2021 Apr 24;1156:338349. Epub 2021 Feb 24.

van 't Hoff Institute for Molecular Science, University of Amsterdam, Amsterdam, the Netherlands; Centre for Analytical Sciences Amsterdam, Amsterdam, the Netherlands.

Bottom-up proteomics provides often small amounts of highly complex samples that cannot be analysed by direct mass spectrometry (MS). To gain a better insight in the sample composition, liquid chromatography (LC) and (comprehensive) two-dimensional liquid chromatography (2D-LC or LC × LC) can be coupled to the MS. Low-flow separations are attractive for HRMS analysis, but they tend to be lengthy. In this work, a low-flow, online, actively modulated LC × LC system, based on hydrophilic-interaction liquid chromatography (HILIC) in the first dimension and reversed-phase liquid chromatography (RPLC) in the second dimension, was developed to separate complex mixtures of peptides. Miniaturization permitted the analysis of small sample amounts (1-5 μg) and direct coupling with micro-ESI MS (1 μL min). All components were focused and automatically transferred from HILIC to RPLC using stationary-phase-assisted active modulation (C18 traps) to deal with solvent-incompatibility or dilution issues. Optimization of the setup was performed for the HILIC columns and the RPLC columns to provide a more efficient separation and higher identification rates than obtained using one-dimensional (1D) LC. A 60% increase in peak capacity was obtained with the 2D setup compared to a 1D-RPLC separation and a 17-34% increase in the number of proteins identified was achieved for the samples analysed (2D-yeast-8280 peptides and 2D-kidney tissue-8843 peptides), without increasing the analysis time (2 h).
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http://dx.doi.org/10.1016/j.aca.2021.338349DOI Listing
April 2021

Peak-tracking algorithm for use in comprehensive two-dimensional liquid chromatography - Application to monoclonal-antibody peptides.

J Chromatogr A 2021 Feb 21;1639:461922. Epub 2021 Jan 21.

van 't Hoff Institute for Molecular Sciences, Analytical Chemistry Group, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, the Netherlands; Centre for Analytical Sciences Amsterdam (CASA), the Netherlands.

A peak-tracking algorithm was developed for use in comprehensive two-dimensional liquid chromatography coupled to mass spectrometry. Chromatographic peaks were tracked across two different chromatograms, utilizing the available spectral information, the statistical moments of the peaks and the relative retention times in both dimensions. The algorithm consists of three branches. In the pre-processing branch, system peaks are removed based on mass spectra compared to low intensity regions and search windows are applied, relative to the retention times in each dimension, to reduce the required computational power by elimination unlikely pairs. In the comparison branch, similarity between the spectral information and statistical moments of peaks within the search windows is calculated. Lastly, in the evaluation branch extracted-ion-current chromatograms are utilized to assess the validity of the pairing results. The algorithm was applied to peptide retention data recorded under varying chromatographic conditions for use in retention modelling as part of method optimization tools. Moreover, the algorithm was applied to complex peptide mixtures obtained from enzymatic digestion of monoclonal antibodies. The algorithm yielded no false positives. However, due to limitations in the peak-detection algorithm, cross-pairing within the same peaks occurred and six trace compounds remained falsely unpaired.
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http://dx.doi.org/10.1016/j.chroma.2021.461922DOI Listing
February 2021

Measuring and using scanning-gradient data for use in method optimization for liquid chromatography.

J Chromatogr A 2021 Jan 2;1636:461780. Epub 2020 Dec 2.

University of Amsterdam, van 't Hoff Institute for Molecular Sciences, Analytical-Chemistry Group, Science Park 904, 1098 XH Amsterdam, the Netherlands; Centre for Analytical Sciences Amsterdam (CASA), The Netherlands; Department of Chemistry, Gustavus Adolphus College, Saint Peter, Minnesota 56082, USA.

The use of scanning gradients can significantly reduce method-development time in reversed-phase liquid chromatography. However, there is no consensus on how they can best be used. In the present work we set out to systematically investigate various factors and to formulate guidelines. Scanning gradients are used to establish retention models for individual analytes. Different retention models were compared by computing the Akaike information criterion and the prediction accuracy. The measurement uncertainty was found to influence the optimum choice of model. The use of a third parameter to account for non-linear relationships was consistently found not to be statistically significant. The duration (slope) of the scanning gradients was not found to influence the accuracy of prediction. The prediction error may be reduced by repeating scanning experiments or - preferably - by reducing the measurement uncertainty. It is commonly assumed that the gradient-slope factor, i.e. the ratio between slopes of the fastest and the slowest scanning gradients, should be at least three. However, in the present work we found this factor less important than the proximity of the slope of the predicted gradient to that of the scanning gradients. Also, interpolation to a slope between that of the fastest and the slowest scanning gradient is preferable to extrapolation. For comprehensive two-dimensional liquid chromatography (LC × LC) our results suggest that data obtained from fast second-dimension gradients cannot be used to predict retention in much slower first-dimension gradients.
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http://dx.doi.org/10.1016/j.chroma.2020.461780DOI Listing
January 2021

Reducing the influence of geometry-induced gradient deformation in liquid chromatographic retention modelling.

J Chromatogr A 2021 Jan 13;1635:461714. Epub 2020 Nov 13.

Van 't Hoff Institute for Molecular Science (HIMS), University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands; Centre for Analytical Sciences Amsterdam (CASA), The Netherlands.

Rapid optimization of gradient liquid chromatographic (LC) separations often utilizes analyte retention modelling to predict retention times as function of eluent composition. However, due to the dwell volume and technical imperfections, the actual gradient may deviate from the set gradient in a fashion unique to the employed instrument. This makes accurate retention modelling for gradient LC challenging, in particular when very fast separations are pursued. Although gradient deformation has been addressed in method-transfer situations, it is rarely taken into account when reporting analyte retention parameters obtained from gradient LC data, hampering the comparison of data from various sources. In this study, a response-function-based algorithm was developed to determine analyte retention parameters corrected for geometry-induced deformations by specific LC instruments. Out of a number of mathematical distributions investigated as response-functions, the so-called "stable function" was found to describe the formed gradient most accurately. The four parameters describing the model resemble the statistical moments of the distribution and are related to chromatographic parameters, such as dwell volume and flow rate. The instrument-specific response function can then be used to predict the actual shape of any other gradient programmed on that instrument. To incorporate the predicted gradient in the retention modelling of the analytes, the model was extended to facilitate an unlimited number of linear gradient steps to solve the equations numerically. The significance and impact of distinct gradient deformation for fast gradients was demonstrated using three different LC instruments. As a proof of principle, the algorithm and retention parameters obtained on a specific instrument were used to predict the retention times on different instruments. The relative error in the predicted retention times went down from an average of 9.8% and 12.2% on the two other instruments when using only a dwell-volume correction to 2.1% and 6.5%, respectively, when using the proposed algorithm. The corrected retention parameters are less dependent on geometry-induced instrument effects.
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http://dx.doi.org/10.1016/j.chroma.2020.461714DOI Listing
January 2021

Asymmetrical flow field-flow fractionation to probe the dynamic association equilibria of β-D-galactosidase.

J Chromatogr A 2021 Jan 13;1635:461719. Epub 2020 Nov 13.

University of Amsterdam, van 't Hoff Institute for Molecular Sciences, Analytical-Chemistry Group, Science Park, 904, 1098 XH Amsterdam, The Netherlands; Centre of Analytical Sciences Amsterdam, Science Park, 904, 1098 XH Amsterdam, The Netherlands.

Protein dynamics play a significant role in many aspects of enzyme activity. Monitoring of structural changes and aggregation of biotechnological enzymes under native conditions is important to safeguard their properties and function. In this work, the potential of asymmetrical flow field-flow fractionation (AF4) to study the dynamic association equilibria of the enzyme β-D-galactosidase (β-D-Gal) was evaluated. Three commercial products of β-D-Gal were investigated using carrier liquids containing sodium chloride or ammonium acetate, and the effect of adding magnesium (II) chloride to the carrier liquid was assessed. Preservation of protein structural integrity during AF4 analysis was essential and the influence of several parameters, such as the focusing step (including use of frit-inlet), cross flow, and injected amount, was studied. Size-exclusion chromatography (SEC) and dynamic light scattering (DLS) were used to corroborate the in-solution enzyme oligomerization observed with AF4. In contrast to SEC, AF4 provided sufficiently mild separation conditions to monitor protein conformations without disturbing the dynamic association equilibria. AF4 analysis showed that ammonium acetate concentrations above 40 mM led to further association of the dimers ("tetramerization") of β-D-Gal. Magnesium ions, which are needed to activate β-D-Gal, appeared to induce dimer association, raising justifiable questions about the role of divalent metal ions in protein oligomerization and on whether tetramers or dimers are the most active form of β-D-Gal.
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http://dx.doi.org/10.1016/j.chroma.2020.461719DOI Listing
January 2021

Recent applications of retention modelling in liquid chromatography.

J Sep Sci 2021 Jan 3;44(1):88-114. Epub 2020 Nov 3.

Analytical Chemistry Group, van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, The Netherlands.

Recent applications of retention modelling in liquid chromatography (2015-2020) are comprehensively reviewed. The fundamentals of the field, which date back much longer, are summarized. Retention modeling is used in retention-mechanism studies, for determining physical parameters, such as lipophilicity, and for various more-practical purposes, including method development and optimization, method transfer, and stationary-phase characterization and comparison. The review focusses on the effects of mobile-phase composition on retention, but other variables and novel models to describe their effects are also considered. The five most-common models are addressed in detail, i.e. the log-linear (linear-solvent-strength) model, the quadratic model, the log-log (adsorption) model, the mixed-mode model, and the Neue-Kuss model. Isocratic and gradient-elution methods are considered for determining model parameters and the evaluation and validation of fitted models is discussed. Strategies in which retention models are applied for developing and optimizing one- and two-dimensional liquid chromatographic separations are discussed. The review culminates in some overall conclusions and several concrete recommendations.
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http://dx.doi.org/10.1002/jssc.202000905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821232PMC
January 2021

Charge-based separation of synthetic macromolecules by non-aqueous ion exchange chromatography.

J Chromatogr A 2020 Aug 18;1626:461351. Epub 2020 Jun 18.

DSM Coating Resins, Analytical Technology Centre, Waalwijk, the Netherlands; University of Amsterdam, van 't Hoff Institute for Molecular Science (HIMS), Amsterdam, the Netherlands; Centre for Analytical Sciences Amsterdam, Amsterdam, the Netherlands.

Traditional polymer-separation methods, such as size-exclusion chromatography and (gradient) liquid adsorption chromatography, cannot provide separations exclusively based on the number of deprotonated carboxylic-acid groups along the backbone chain of polymers. A novel separation method, based on non-aqueous ion-exchange chromatography (NAIEX), was developed, which allows such a separation of acid-functional polymers that are soluble in organic solvents. The polar, aprotic N-methyl-2-pyrrolidone was found to be a suitable solvent. It features a high relative permittivity (favouring dissociation of ion pairs into free ions) and it is a good solvent for polymers and organic salts, such as triethyl-ammonium formate. A negative charge is established on these polymers by deprotonation of the carboxylic-acid groups in the presence of an organic superbase (tetramethyl guanidine). Traditional potent organic bases, such as triethylamine, do not possess the base strength to compensate for the increase in pK of polymeric carboxylic acid groups in non-aqueous conditions. Triethyl-ammonium formate is proposed as an alternative to traditional salts used for elution in aqueous ion-exchange chromatography. Separation was performed on an industry-standard strong-anion-exchange column and (near-)universal detection of the polymers was performed by high-temperature evaporative-light-scattering detection. The NAIEX method yielded a separation based on the acid-functionality distribution of the polymer. NAIEX was compared with traditional normal- and reversed-phase liquid-chromatography approaches for the separation of acid-functional copolymers.
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http://dx.doi.org/10.1016/j.chroma.2020.461351DOI Listing
August 2020

Recent applications of chemometrics in one- and two-dimensional chromatography.

J Sep Sci 2020 May 19;43(9-10):1678-1727. Epub 2020 Mar 19.

Analytical Chemistry Group, van 't Hoff Institute for Molecular Sciences, Faculty of Science, University of Amsterdam, Amsterdam, The Netherlands.

The proliferation of increasingly more sophisticated analytical separation systems, often incorporating increasingly more powerful detection techniques, such as high-resolution mass spectrometry, causes an urgent need for highly efficient data-analysis and optimization strategies. This is especially true for comprehensive two-dimensional chromatography applied to the separation of very complex samples. In this contribution, the requirement for chemometric tools is explained and the latest developments in approaches for (pre-)processing and analyzing data arising from one- and two-dimensional chromatography systems are reviewed. The final part of this review focuses on the application of chemometrics for method development and optimization.
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http://dx.doi.org/10.1002/jssc.202000011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317490PMC
May 2020

Emerging techniques for the detection of pyrotechnic residues from seized postal packages containing fireworks.

Forensic Sci Int 2020 03 24;308:110160. Epub 2020 Jan 24.

University of Amsterdam, Faculty of Science, Van 't Hoff Institute for Molecular Sciences, Amsterdam, the Netherlands; CLHC, Amsterdam Center for Forensic Science and Medicine, University of Amsterdam, P.O. Box 94157, 1090 GD Amsterdam, the Netherlands.

High volume screening of parcels with the aim to trace the illegal distribution and selling of fireworks using postal services is challenging. Inspection services have limited manpower and means to perform extensive visual inspection. In this study, the presence of solid pyrotechnic residues collected from cardboard shipping parcels containing fireworks was investigated for direct in-field chemical detection. Two emerging trace detection techniques, i.e., capillary electrophoresis (CE)-based inorganic oxidizer detector and infrared thermal desorption (IRTD) coupled with direct analysis in real time mass spectrometry (DART-MS), were investigated for their potential as screening tools. Detection of non-visible pyrotechnic trace residues from real-case seized parcels was demonstrated using both screening techniques. However, the high nitrate background in the commercial CE system complicated its screening for black powder traces. IRTD-DART-MS allowed differentiation between flash and black powder by identification of the molecular inorganic ions. Compared to the portable CE instrument, rapid screening using IRTD-DART-MS is currently limited to laboratory settings. The capabilities of these emerging techniques established solid particle and trace residue chemical detection as interesting options for parcel screening in a logistic setting.
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http://dx.doi.org/10.1016/j.forsciint.2020.110160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041295PMC
March 2020

Confinement of Monolithic Stationary Phases in Targeted Regions of 3D-Printed Titanium Devices Using Thermal Polymerization.

Anal Chem 2020 02 13;92(3):2589-2596. Epub 2020 Jan 13.

Van't Hoff Institute for Molecular Sciences , University of Amsterdam , 1090GD Amsterdam , The Netherlands.

In this study, we have prepared thermally initiated polymeric monolithic stationary phases within discrete regions of 3D-printed titanium devices. The devices were created with controllable hot and cold regions. The monolithic stationary phases were first locally created in capillaries inserted into the channels of the titanium devices. The homogeneity of the monolith structure and the interface length were studied by scanning a capacitively coupled conductivity contactless detector (CD) along the length of the capillary. Homogeneous monolithic structures could be obtained within a titanium device equipped with a hot and cold jacket connected to two water baths. The confinement method was optimized in capillaries. The sharpest interfaces (between monolith and empty channel) were obtained with the hot region maintained at 70 °C and the cold region at 4 or 10 °C, with the latter temperature yielding better repeatability. The optimized conditions were used to create monoliths bound directly to the walls of the titanium channels. The fabricated monoliths were successfully used to separate a mixture of four intact proteins using reversed-phase liquid chromatography. Further chromatographic characterization showed a permeability () of ∼4 × 10 m and a total porosity of 60%.
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http://dx.doi.org/10.1021/acs.analchem.9b04298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003155PMC
February 2020

Optimizing design and employing permeability differences to achieve flow confinement in devices for spatial multidimensional liquid chromatography.

J Chromatogr A 2020 Feb 31;1612:460665. Epub 2019 Oct 31.

Universiteit van Amsterdam, Van 't Hoff Institute for Molecular Sciences, Science Park 904, 1098 XH Amsterdam, the Netherlands.

In spatial multi-dimensional liquid chromatography (LC) devices the flow of each dimension has to remain in the corresponding region, otherwise the separation efficiency is undermined. Adequate flow-confinement measures are necessary. Here, the use of permeability differences across different compartments of spatial two-dimensional (2D) and three-dimensional (3D) LC devices as a method to guide fluid flow and reduce analyte loss during the first, second- and third-dimension development was investigated with computational fluid dynamics (CFD) simulations. In case of 2DLC devices, it was shown that porous barriers with a permeability on the order of 10 m suffice to keep the total sample spillage from an open D channel under 1%. In case of 3DLC devices, it was shown that flow confinement could be achieved using an open D channel in combination with a highly-permeable monolith (permeability on the order of 10 m) in the second-dimension (D) and a less permeable packing with a permeability on the order of 10 m (e.g. 1 μm particles) in the third-dimension (D). Additionally, the impact of the D flow-distributor has been studied and a novel design, capable of limiting the spillage to the other dimensions to the absolute minimum, is proposed.
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http://dx.doi.org/10.1016/j.chroma.2019.460665DOI Listing
February 2020

Accurate modelling of the retention behaviour of peptides in gradient-elution hydrophilic interaction liquid chromatography.

J Chromatogr A 2020 Mar 23;1614:460650. Epub 2019 Oct 23.

Van 't Hoff Institute for Molecular Sciences, Science Park 904, 1098 XH Amsterdam, the Netherlands; Centre for Analytical Science Amsterdam, Science Park 904, 1098 XH Amsterdam, the Netherlands.

The applicability of models to describe peptide retention in hydrophilic interaction liquid chromatography (HILIC) was investigated. A tryptic digest of bovine-serum-albumin (BSA) was used as a test sample. Several different models were considered, including adsorption, mixed-mode, exponential, quadratic and Neue-Kuss models. Gradient separations were performed on three different HILIC stationary-phases under three different mobile-phase conditions to obtain model parameters. Methods to track peaks for specific peptides across different chromatograms are shown to be essential. The optimal mobile-phase additive for the separation of BSA digest on each of the three columns was selected by considering the retention window, peak width and peak intensity with mass-spectrometric detection. The performance of the models was investigated using the Akaike information criterion (AIC) to measure the goodness-of-fit and evaluated using prediction errors. The F-test for regression was applied to support model selection. RPLC separations of the same sample were used to test the models. The adsorption model showed the best performance for all the HILIC columns investigated and the lowest prediction errors for two of the three columns. In most cases prediction errors were within 1%.
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http://dx.doi.org/10.1016/j.chroma.2019.460650DOI Listing
March 2020

Multichannel separation device with parallel electrochemical detection.

J Chromatogr A 2020 Jan 9;1610:460537. Epub 2019 Sep 9.

Masaryk University, Department of Chemistry, Brno, Czech Republic. Electronic address:

A device with four parallel channels was designed and manufactured by 3D printing in titanium. A simple experimental setup allowed splitting of the mobile phase in four parallel streams, such that a single sample could be analysed four times simultaneously. The four capillary channels were filled with a monolithic stationary phase, prepared using a zwitterionic functional monomer in combination with various dimethacrylate cross-linkers. The resulting stationary phases were applicable in both reversed-phase and hydrophilic-interaction retention mechanisms. The mobile-phase composition was optimized by means of a window diagram so as to obtain the highest possible resolution of dopamine precursors and metabolites on all columns. Miniaturized electrochemical detectors with carbon fibres as working electrodes and silver micro-wires as reference electrodes were integrated in the device at the end of each column. Experimental separations were successfully compared with those predicted by a three-parameter retention model. Finally, dopamine was determined in human urine to further confirm applicability of the developed device.
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http://dx.doi.org/10.1016/j.chroma.2019.460537DOI Listing
January 2020

Distinguishing drug isomers in the forensic laboratory: GC-VUV in addition to GC-MS for orthogonal selectivity and the use of library match scores as a new source of information.

Forensic Sci Int 2019 Sep 26;302:109900. Epub 2019 Jul 26.

Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Postbus 94157, Amsterdam 1090 GD, Netherlands; Co van Ledden Hulsebosch Center (CLHC), Amsterdam Center for Forensic Science and Medicine, Postbus 94157, Amsterdam 1090 GD, Netherlands.

Currently, forensic drug experts are facing chemical identification challenges with the increasing number of new isomeric forms of psychoactive substances occurring in case samples. Very similar mass spectra for these substances could easily result in misidentification using the regular GC-MS screening methods in combination with colorimetric testing in forensic laboratories. Building on recent work from other groups, this study demonstrates that GC-VUV is a powerful technique for drug isomer differentiation, showing reproducible and discriminating spectra for aromatic ring-isomers. MS and VUV show complementary selectivity as VUV spectra are ring-position specific whereas MS spectra are characteristic for the amine moieties of the molecule. VUV spectra are very reproducible showing less than 0.1‰ deviation in library match scores and therefore small spectral differences suffice to confidently distinguish isomers. In comparison, MS match scores gave over 10‰ deviation and showed significant overlap in match score ranges for several isomers. This poses a risk for false positive identifications when assigning compounds based on retention time and GC-MS mass spectrum. A strategy was developed, based on Kernel Density Estimations of match scores, to construct Receiver Operating Characteristic (ROC) curves and estimate likelihood ratios (LR values) with respect to the chemical differentiation of drug related isomers. This approach, and the added value of GC-VUV is demonstrated with the chemical analysis of several samples from drug case work from the Amsterdam area involving both compounds listed in Dutch drug legislation (3,4-MDMA; 3,4-MDA; 4-MMC; 4-MEC and 4-FA) as well as their unlisted and thus uncontrolled isomers (2,3-MDMA; 2,3-MDA; 2- and 3-MMC; 2- and 3-MEC and 2- and 3-FA).
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http://dx.doi.org/10.1016/j.forsciint.2019.109900DOI Listing
September 2019

Perspectives on the future of multi-dimensional platforms.

Faraday Discuss 2019 08;218(0):72-100

University of Amsterdam, van 't Hoff Institute for Molecular Sciences, Analytical-Chemistry Group, Science Park 904, 1098 XH Amsterdam, The Netherlands.

Two-dimensional liquid chromatography (2D-LC) formats have emerged to help address separation problems that are too complex for conventional one-dimensional LC. There are a number of obstacles to the proliferation of 2D-LC that are gradually being removed. Reliable commercial instrumentation has become available and data analysis software is being improved. Detector-sensitivity and phase-system compatibility issues can largely be solved by using active-modulation strategies. The remaining challenge, developing good and fast 2D-LC methods within a reasonable time, may be solved with smart algorithms. The technology platform that has been developed for 2D-LC also creates a number of other possibilities. Between the two separation stages, all kinds of physical (e.g. dissolution) or chemical (e.g. enzymatic or light-induced degradation) processes can be made to take place, allowing a wide variety of experiments to be performed within a single, efficient and automated analysis. All these developments are discussed in this paper and a number of critical issues are identified. A practical example, the characterization of polysorbates by high-resolution comprehensive two-dimensional liquid chromatography in combination with high-resolution mass spectrometry, is described as a culmination of recent developments in 2D-LC and as an illustration of the current state of the art.
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http://dx.doi.org/10.1039/c8fd00233aDOI Listing
August 2019

Experimental and numerical study of band-broadening effects associated with analyte transfer in microfluidic devices for spatial two-dimensional liquid chromatography created by additive manufacturing.

J Chromatogr A 2019 Aug 22;1598:77-84. Epub 2019 Mar 22.

Universiteit van Amsterdam, Van' t Hoff Institute for Molecular Sciences, Science Park 904, 1098 XH, Amsterdam, the Netherlands.

Conventional one-dimensional column-based liquid chromatographic (LC) systems do not offer sufficient separation power for the analysis of complex mixtures. Column-based comprehensive two-dimensional liquid chromatography offers a higher separation power, yet suffers from instrumental complexity and long analysis times. Spatial two-dimensional liquid chromatography can be considered as an alternative to column-based approaches. The peak capacity of the system is ideally the product of the peak capacities of the two dimensions, yet the analysis time remains relatively short due to parallel second-dimension separations. Aspects affecting the separation efficiency of this type of systems include flow distribution to homogeneously distribute the mobile phase for the second-dimension (D) separation, flow confinement during the first-dimension (D) separation, and band-broadening effects during analyte transfer from the D separation channel to the D separation area. In this study, the synergy between computational fluid dynamics (CFD) simulations and rapid prototyping was exploited to address band broadening during the D development and analyte transfer from D to D. Microfluidic devices for spatial two-dimensional liquid chromatography were designed, simulated, 3D-printed and tested. The effects of presence and thickness of spacers in the D separation area were addressed and leaving these out proved to be the most efficient solution regarding band broadening reduction. The presence of a stationary-phase material in the D channel had a great effect on the analyte transfer from the D to the D and the resulting band broadening. Finally, pressure limit of the fabricated devices and printability are discussed.
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http://dx.doi.org/10.1016/j.chroma.2019.03.041DOI Listing
August 2019

Analysis of charged acrylic particles by on-line comprehensive two-dimensional liquid chromatography and automated data-processing.

Anal Chim Acta 2019 Apr 9;1054:184-192. Epub 2019 Jan 9.

University of Amsterdam, van 't Hoff Institute for Molecular Sciences, Analytical-Chemistry Group, Science Park 904, 1098 XH, Amsterdam, the Netherlands.

A thorough understanding of particle formation and polymer growth during emulsion polymerization is indispensable for the development of particles and products with very specific properties. This has created a demand for the detailed characterization of various properties and property distributions - and the relation between these. A method is described that enables comprehensive, simultaneous determination of the size distribution of nanoparticles and the molecular-weight distribution of the constituting polymers as a function of the particle size. The result is a complete two-dimensional distribution that details the interdependence of the two parameters. The approach comprehensively combines hydrodynamic chromatography with size-exclusion chromatography. An automated band-broadening filter has been developed to improve the accuracy of the measured distributions. The algorithm utilizes automated curve-fitting approaches to describe detected particle distributions for each horizontal slice of the 2D-LC chromatogram, and filters band broadening using calibration curves. The method has been applied to samples of complex nanoparticles comprising hydrophobic, hydrophilic and charged moieties, viz. stabilized dispersions of poly[(methyl methacrylate)-co-(butyl acrylate)-co-(methacrylic acid)]-nanoparticles in water. We consistently found that, within a single population of particles, the weight-average molecular weight increases with particle size.
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http://dx.doi.org/10.1016/j.aca.2018.12.059DOI Listing
April 2019

On-line microfluidic immobilized-enzyme reactors: A new tool for characterizing synthetic polymers.

Anal Chim Acta 2019 Apr 12;1053:62-69. Epub 2018 Dec 12.

Universiteit van Amsterdam, Van 't Hoff Institute for Molecular Sciences, Science Park 904, 1098 XH, Amsterdam, the Netherlands.

Biodegradable polymeric materials may eventually replace biostable materials for medical applications, including therapeutic devices, scaffolds for tissue engineering, and drug-delivery vehicles. To further develop such materials, a more fundamental understanding is necessary to correlate parameters including chemical-composition distribution within a macromolecular structure with the final properties of the material, including particle-size. A wide variety of analytical techniques have been applied for the characterization of polymer materials, including hyphenated techniques such as comprehensive two-dimensional liquid chromatography (LC × LC). In this context, we have investigated enzymatic degradation of polyester-based nanoparticles, both in-solution and by the use of an immobilized-enzyme reactor (IMER). We have demonstrated for the first time the implementation of such an IMER in a size-exclusion chromatography system for on-line degradation and subsequent analysis of the polymer degradation products. The effect of residence times ranging from 12 s to 4 min on polymer degradation was assessed. IMER-assisted degradation is much faster compared to in-solution degradation, which requires several hours to days, and opens the possibility to use such reactors in LC × LC modulation interfaces.
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http://dx.doi.org/10.1016/j.aca.2018.12.002DOI Listing
April 2019

Characterization of Dye Extracts from Historical Cultural-Heritage Objects Using State-of-the-Art Comprehensive Two-Dimensional Liquid Chromatography and Mass Spectrometry with Active Modulation and Optimized Shifting Gradients.

Anal Chem 2019 02 1;91(4):3062-3069. Epub 2019 Feb 1.

van 't Hoff Institute for Molecular Sciences, Analytical-Chemistry Group , University of Amsterdam , Science Park 904 , 1098 XH , Amsterdam , The Netherlands.

Unbiased characterization of dyes and their degradation products in cultural-heritage objects requires an analytical method which provides universal separation power regardless of dye classes. Dyes are small molecules that vary widely in chemical structure and properties, which renders their characterization by a single method challenging. We have developed a comprehensive two-dimensional liquid chromatography method hyphenated with mass spectrometry and UV-vis detection. We use stationary-phase-assisted modulation to enhance the method in terms of detection limits and solvent compatibility and to reduce the analysis time. The PIOTR program was used to optimize an assembly of shifting second-dimension gradients, which resulted in a high degree of orthogonality (80% in terms of the asterisk concept). The resulting method is universally applicable to all classes of dyes extracted from cultural-heritage objects. Thanks to the high peak capacity and orthogonality, dye components can be separated from chemically similar impurities and degradation products, providing a detailed fingerprint of the dyes mixture in a specific sample. The method was applied to a number of challenging dye extracts from 17th- and 19th-century cultural-heritage objects.
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http://dx.doi.org/10.1021/acs.analchem.8b05469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383186PMC
February 2019

Peak-Tracking Algorithm for Use in Automated Interpretive Method-Development Tools in Liquid Chromatography.

Anal Chem 2018 12 15;90(23):14011-14019. Epub 2018 Nov 15.

van 't Hoff Institute for Molecular Sciences, Analytical Chemistry Group , University of Amsterdam , Science Park 904 , 1098 XH Amsterdam , The Netherlands.

A peak-tracking algorithm for chromatograms recorded using liquid chromatography and mass spectrometry was developed. Peaks are tracked across chromatograms using the spectrometric information, the statistical moments of the chromatographic peaks, and the relative retention. The algorithm can be applied to pair chromatographic peaks in two very different chromatograms, obtained for different samples using different methods. A fast version of the algorithm was specifically tailored to process chromatograms obtained during method development or optimization, where a few similar mobile-phase-composition gradients (same eluent components, but different ranges and programming rates) are applied to the same sample for the purpose of obtaining model parameters to describe the retention of sample components. Due to the relative similarity between chromatograms, time-saving preselection protocols can be used to locate a candidate peak in another chromatogram. The algorithm was applied to two different samples featuring isomers. The automatically tracked peaks and the resulting retention parameters generally yielded prediction errors of less than 1%.
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http://dx.doi.org/10.1021/acs.analchem.8b03929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282104PMC
December 2018

Recent Developments in Two-Dimensional Liquid Chromatography: Fundamental Improvements for Practical Applications.

Anal Chem 2019 01 14;91(1):240-263. Epub 2018 Nov 14.

University of Amsterdam , van 't Hoff Institute for Molecular Sciences, Analytical-Chemistry Group , Science Park 904 , 1098 XH Amsterdam , The Netherlands.

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http://dx.doi.org/10.1021/acs.analchem.8b04841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322149PMC
January 2019

Two-dimensional insertable separation tool (TWIST) for flow confinement in spatial separations.

J Chromatogr A 2018 Nov 26;1577:120-123. Epub 2018 Sep 26.

Van't Hoff Institute for Molecular Sciences (HIMS), Faculty of Science, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, the Netherlands.

Spatial comprehensive two-dimensional liquid chromatography (LC×LC) may be an efficient approach to achieve high peak capacities in relatively short analysis times, thanks to parallel second-dimension separations [1,2]. A key issue to reach the potential of LC×LC is to achieve adequate flow control and confinement of the analytes to the desired regions, i.e. confinement in the first-dimension direction and subsequently homogeneous flow in the second dimension. To achieve these goals we propose the TWIST concept (TWo-dimensional Insertable Separation Tool), a modular device that includes an internal first-dimension (D) part that is cylindrical and rotatable. This internal part features a series of through-holes, each of which is perpendicular to the direction of the D flow. The internal part is inserted in the cylindrical casing of the external part. The internal diameter of the casing is marginally larger than the external diameter of the internal part. The external part also comprises a flow distributor and second-dimension (D) channels. During the D injection and development, the channel is placed in a position where the through-holes are facing the wall of the external part, such that the liquid remains confined within the D channel. Thereafter, to realize the transfer to the second dimension (D injection), the D channel is rotated, so that the holes of the internal part are aligned with the holes on the external part, allowing a transversal flow of the D mobile phase from the distributor through the D channel and eventually into the D area.
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http://dx.doi.org/10.1016/j.chroma.2018.09.054DOI Listing
November 2018

Characterization of complex polyether polyols using comprehensive two-dimensional liquid chromatography hyphenated to high-resolution mass spectrometry.

J Chromatogr A 2018 Sep 18;1569:128-138. Epub 2018 Jul 18.

University of Amsterdam, Van't Hoff Institute for Molecular Sciences, Science Park 904, 1098 XH Amsterdam, The Netherlands.

Polyether polyols are often used in formulated systems, but their complete characterization is challenging, because of simultaneous heterogeneities in chemical composition, molecular weight and functionality. One-dimensional liquid chromatography-mass spectrometry is commonly used to characterize polyether polyols. However, the separation power of this technique is not sufficient to resolve the complexity of such samples entirely. In this study, comprehensive two-dimensional liquid chromatography hyphenated with high-resolution mass spectrometry (LC × LC-HRMS) was used for the characterization of (i) castor oil ethoxylates (COEs) reacted with different mole equivalents of ethylene oxide and (ii) a blended formulation consisting of glycerol ethoxylate, glycerol propoxylate and glycerol ethoxylate-random-propoxylate copolymers. Retention in the first (hydrophilic-interaction-chromatography) dimension was mainly governed by degree of ethoxylation, while the second reversed-phase dimension resolved the samples based on degree of propoxylation (blended formulation) or alkyl chain length (COEs). For different COE samples, we observed the separation of isomer distributions of various di-, tri- and tetra-esters, and such positional isomers were studied by tandem mass spectrometry (LC-MS/MS). This revealed characteristic fragmentation patterns, which allowed discrimination of the isomers based on terminal or internal positioning of the fatty-acid moieties and provided insight in the LC × LC retention behavior of such species.
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http://dx.doi.org/10.1016/j.chroma.2018.07.054DOI Listing
September 2018

Comprehensive two-dimensional liquid chromatography of heavy oil.

J Chromatogr A 2018 Aug 5;1564:110-119. Epub 2018 Jun 5.

Universiteit van Amsterdam, Van' t Hoff Institute for Molecular Sciences, Analytical-Chemistry Group, Science Park 904, 1098 XH, Amsterdam, The Netherlands.

Heavy oil refers to the part of crude oil that is not amenable to further distillation. Processing of these materials to useful products provides added value, but requires advanced technology as well as extensive characterization in order to optimize the yield of the most profitable products. The use of comprehensive two-dimensional liquid chromatography (LC × LC) was investigated for the characterization of de-asphalted short residue, also called maltenes. Initial studies were performed on a polycyclic aromatic hydrocarbon standard, an aromatic extract of hydrowax, and the fractions obtained after solvent fractionation of the maltenes. Cyanopropyl- and octadecyl-silica were used as first-dimension and second-dimension columns, respectively. The analysis of the maltenes and fractions thereof required a change in first-dimension stationary phase to biphenyl as well as an increase in modifier strength to improve recovery. The extensive characterization of maltenes with LC × LC within four hours was demonstrated. The Program for the Interpretive Optimization of Two-dimensional Resolution (PIOTR) has been applied to aid the method development, but due to the absence of specific peaks in the chromatograms it was challenging to apply to the maltenes or its fractions. Nonetheless, an approach is suggested for resolution optimization in cases such as the present one, in which regions of co-elution are observed, rather than clearly separated peaks.
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http://dx.doi.org/10.1016/j.chroma.2018.06.001DOI Listing
August 2018