Exploring the Effects of Cyclosporin A to Isocyclosporin A Rearrangement on Ion Mobility Separation.

Cyclosporin A (CycA) is a peptide secondary metabolite derived from fungi that plays a crucial role in transplantation surgery. Cyclic traveling wave ion mobility mass spectrometry (IM-MS) revealed an N → O peptidyl shift in singly protonated CycA to isocyclosporin A (isoA), whereas no such isomerization was observed for doubly protonated and sodiated molecules. CycA and isoA were able to be separated by considering doubly protonated precursors using a specific ion fragment. In parallel, sodium ion stabilization facilitated the simultaneous separation and quantitation of singly charged cyclosporin isomers with the limit of detection and coefficient of determination of 1.3% and 0.9908 for CycA in isoA and 1.0% and 0.9830 for isoA in CycA, respectively. Finally, 1H-13C gHSQC NMR experiments permitted parallel recording of up to 11 cyclosporin conformers. The ratios were determined by integrating the volume of cross-peaks of the upfield resonating hydrogen in the diastereotopic methylene group of sarcosine-3.

Experimental hierarchy of the nonclassicality of single-qubit states via potentials for entanglement, steering, and Bell nonlocality.

Entanglement potentials are a promising way to quantify the nonclassicality of single-mode states. They are defined by the amount of entanglement (expressed by, e.g., the Wootters concurrence) obtained after mixing the examined single-mode state with a purely classical state; such as the vacuum or a coherent state. We generalize the idea of entanglement potentials to other quantum correlations: the EPR steering and Bell nonlocality, thus enabling us to study mutual hierarchies of these nonclassicality potentials. Instead of the usual vacuum and one-photon superposition states, we experimentally test this concept using specially tailored polarization-encoded single-photon states. One polarization encodes a given nonclassical single-mode state, while the other serves as the vacuum place-holder. This technique proves to be experimentally more convenient in comparison to the vacuum and a one-photon superposition as it does not require the vacuum detection.

Investigation of chromatographic peak broadening in supercritical fluid chromatography/atmospheric pressure chemical ionization mass spectrometry.

Multimode ionization source allows for switching between different ionization techniques, for example, electrospray and atmospheric pressure chemical ionization, within a single analysis. Supercritical fluid chromatography can handle a wide polarity range of substances from hydrophilic to lipophilic in a single run and can undoubtedly benefit from versatility of this ion source. Nevertheless, we observed a significant chromatographic peak broadening effect in atmospheric pressure chemical ionization mode during supercritical fluid chromatography-mass spectrometry analysis of volatile flavor compounds with a dual ion source named ESCi (Waters). Surprisingly, this effect was not related to the separation process but was triggered solely by the ion source conditions. Neither of photodiode array detector, electrospray mode nor a dedicated atmospheric pressure chemical ionization source suffered from such a phenomenon. Chromatographic peak profiles of ten test substances obtained with the dual ion source were compared with photodiode array detector data as a reference. The broadening effect was more pronounced for volatile compounds with low polarity. Dependence of peak broadening on the ion source settings was systematically investigated. Tuning of desolvation gas flow and its temperature dramatically reduced peak distortion and increased detection sensitivity.

Experimental hybrid quantum-classical reinforcement learning by boson sampling: how to train a quantum cloner.

We report on experimental implementation of a machine-learned quantum gate driven by a classical control. The gate learns optimal phase-covariant cloning in a reinforcement learning scenario having fidelity of the clones as reward. In our experiment, the gate learns to achieve nearly optimal cloning fidelity allowed for this particular class of states. This makes it a proof of present-day feasibility and practical applicability of the hybrid machine learning approach combining quantum information processing with classical control. The quantum information processing performed by the setup is equivalent to boson sampling, which, in complex systems, is predicted to manifest quantum supremacy over classical simulation of linear-optical setups.

Demonstration of Controlled Quantum Teleportation for Discrete Variables on Linear Optical Devices.

We report an experimental implementation of tripartite controlled quantum teleportation on quantum optical devices. The protocol is performed through bi- and tripartite entangled channels of discrete variables and qubits encoded in the polarization of individual photons. The experimental results demonstrate successful controlled quantum teleportation with a fidelity around 83%, well above the classical limit. By realizing the controlled quantum teleportation through a biseparable state, we show that tripartite entanglement is not a necessary resource for controlled quantum teleportation, and the controller's capability to allow or prohibit the teleportation cannot be considered to be a manifestation of tripartite entanglement. These results open new possibilities for further application of controlled quantum teleportation by lowering the teleportation channel's requirements.

Experimental Measurement of the Hilbert-Schmidt Distance between Two-Qubit States as a Means for Reducing the Complexity of Machine Learning.

We report on the experimental measurement of the Hilbert-Schmidt distance between two two-qubit states by many-particle interference. We demonstrate that our three-step method for measuring distances in the Hilbert space is far less complex than reconstructing density matrices and that it can be applied in quantum-enhanced machine learning to reduce the complexity of calculating Euclidean distances between multidimensional points, which can be especially interesting for near term quantum technologies and quantum artificial intelligence research. Our results are also a novel example of applying mixed states in quantum information processing. Usually working with mixed states is undesired, but here it gives the possibility of encoding extra information as the degree of coherence between the given two dimensions of the density matrix.

Comparative study of ink photoinitiators in food packages using gas chromatography with vacuum ultraviolet detection and gas chromatography with mass spectrometry.

This work focused on the development and validation of the analytical procedure using gas chromatography equipped with vacuum-ultraviolet detection for the specific and sensitive determination of nine photoinitiators in food packages. Subsequently, a comparison of the combination of vacuum ultraviolet spectroscopy with gas chromatography and a developed gas chromatography with mass spectrometry method was performed. The vacuum-ultraviolet spectra of all tested photoinitiators were collected and found to be highly distinct, even for isomers. Under the optimal conditions, the limits of detection for nine photoinitiators ranged from 1 to 5 mg/L using vacuum ultraviolet detection and from 0.15 to 0.5 mg/L using mass spectrometric detection. Both techniques were successfully applied for screening of photoinitiators in seven kinds of food packages and the obtained data showed good agreement (the relative difference was between 3 and 18%). The variability in concentrations found in triplicate samples was assessed to be below 18%. Predominantly benzophenone was found in all analysed samples in the range of 0.31-4.23 mg/kg. It appears to be preferably selected by food packaging manufacturers. This study proposes a new simple and sensitive technique used for analysis of photoinitiators that could be a good alternative to gas chromatography with mass spectrometry.

Analysis of new psychoactive substances in human urine by ultra-high performance supercritical fluid and liquid chromatography: Validation and comparison.

New psychoactive substances represent serious social and health problem as tens of new compounds are detected in Europe annually. They often show structural proximity or even isomerism, which complicates their analysis. Two methods based on ultra high performance supercritical fluid chromatography and ultra high performance liquid chromatography with mass spectrometric detection were validated and compared. A simple dilute-filter-and-shoot protocol utilizing propan-2-ol or methanol for supercritical fluid or liquid chromatography, respectively, was proposed to detect and quantify 15 cathinones and phenethylamines in human urine. Both methods offered fast separation (<3 min) and short total analysis time. Precision was well <15% with a few exceptions in liquid chromatography. Limits of detection in urine ranged from 0.01 to 2.3 ng/mL, except for cathinone (5 ng/mL) in supercritical fluid chromatography. Nevertheless, this technique distinguished all analytes including four pairs of isomers, while liquid chromatography was unable to resolve fluoromethcathinone regioisomers. Concerning matrix effects and recoveries, supercritical fluid chromatography produced more uniform results for different compounds and at different concentration levels. This work demonstrates the performance and reliability of supercritical fluid chromatography and corroborates its applicability as an alternative tool for analysis of new psychoactive substances in biological matrixes.

Batch-processing of imaging or liquid-chromatography mass spectrometry datasets and De Novo sequencing of polyketide siderophores.

The open-source and cross-platform software CycloBranch was utilized for dereplication of organic compounds from mass spectrometry imaging imzML datasets and its functions were illustrated on microbial siderophores. The pixel-to-pixel batch-processing was analogous to liquid chromatography mass spectrometry data. Each data point represented here by accurate m/z values and the corresponding ion intensities was matched against integrated compound libraries. The fine isotopic structure matching was also embedded into CycloBranch dereplication process. The siderophores' characterization from single-pixel mass spectra was further supported by their de novo sequencing. New ketide building block library was utilized by CycloBranch to characterize the siderophores in images and mixtures and nomenclature of fragment ion series of linear and cyclic polyketide siderophores was proposed. The software is freely available at http://ms.biomed.cas.cz/cyclobranch. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

Characterization of microbial siderophores by mass spectrometry.

Siderophores play important roles in microbial iron piracy, and are applied as infectious disease biomarkers and novel pharmaceutical drugs. Inductively coupled plasma and molecular mass spectrometry (ICP-MS) combined with high resolution separations allow characterization of siderophores in complex samples taking advantages of mass defect data filtering, tandem mass spectrometry, and iron-containing compound quantitation. The enrichment approaches used in siderophore analysis and current ICP-MS technologies are reviewed. The recent tools for fast dereplication of secondary metabolites and their databases are reported. This review on siderophores is concluded with their recent medical, biochemical, geochemical, and agricultural applications in mass spectrometry context.

Aspergillus infection monitored by multimodal imaging in a rat model.

Although myriads of experimental approaches have been published in the field of fungal infection diagnostics, interestingly, in 21st century there is no satisfactory early noninvasive tool for Aspergillus diagnostics with good sensitivity and specificity. In this work, we for the first time described the fungal burden in rat lungs by multimodal imaging approach. The Aspergillus infection was monitored by positron emission tomography and light microscopy employing modified Grocott's methenamine silver staining and eosin counterstaining. Laser ablation inductively coupled plasma mass spectrometry imaging has revealed a dramatic iron increase in fungi-affected areas, which can be presumably attributed to microbial siderophores. Quantitative elemental data were inferred from matrix-matched standards prepared from rat lungs. The iron, silver, and gold MS images collected with variable laser foci revealed that particularly silver or gold can be used as excellent elements useful for sensitively tracking the Aspergillus infection. The limit of detection was determined for both (107) Ag and (197) Au as 0.03 µg/g (5 µm laser focus). The selective incorporation of (107) Ag and (197) Au into fungal cell bodies and low background noise from both elements were confirmed by energy dispersive X-ray scattering utilizing the submicron lateral resolving power of scanning electron microscopy. The low limits of detection and quantitation of both gold and silver make ICP-MS imaging monitoring a viable alternative to standard optical evaluation used in current clinical settings.

Structural Analysis of Natural Products.

Current mass spectrometry, nuclear magnetic resonance spectroscopy, and X-ray diffraction are presented as structure elucidation tools for analytical chemistry of natural products. Discovering new molecular entities combined with dereplication of known organic compounds represent prerequisites for biological assays and for respective applications as pharmaceuticals or molecular markers. Liquid chromatography is briefly addressed with respect to its use in mass spectrometry- and nuclear magnetic resonance-based metabolomics studies.

Quantification of structurally related aliphatic amino alcohols in l-valinol by hydrophilic interaction liquid chromatography separation combined with postcolumn derivatization and fluorescence detection.

The amino alcohols in l-valinol were effectively separated and quantified using hydrophilic interaction chromatography with fluorescence detection. The influence of the mobile phase (salt type, buffer concentration, and pH) on retention was studied. A column TSKgel amide and mobile phase consisting of 10 mM acetate buffer pH 4.0 and acetonitrile (20:80, v/v) provided well-separated symmetric peaks of analytes. Fluorescence detection was performed using postcolumn derivatization with o-phtaldialdehyde/2-mercaptoethanol at an excitation and emission wavelength of 345 and 450 nm, respectively. Simple sample pretreatment and very high sensitivity represent the main advantages of the developed method. After validation, the method was successfully applied to the analysis of commercial samples of l-valinol.

Fast simultaneous LC/MS/MS determination of 10 active compounds in human serum for therapeutic drug monitoring in psychiatric medication.

A UPLC/MS/MS method with simple protein precipitation has been validated for the fast simultaneous analysis of agomelatine, asenapine, amisulpride, iloperidone, zotepine, melperone, ziprasidone, vilazodone, aripiprazole and its metabolite dehydro-aripiprazole in human serum. Alprenolol was applied as an internal standard. A BEH C18 (2.1 × 50 mm, 1.7 µm) column provided chromatographic separation of analytes using a binary mobile phase gradient (A, 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B, 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Mass spectrometric detection was performed in the positive electrospray ionization mode and ion suppression owing to matrix effects was evaluated. The validation criteria were determined: linearity, precision, accuracy, recovery, limit of detection, limit of quantification, reproducibility and matrix effect. The concentration range was as follows: 0.25-1000 ng/mL for agomelatine; 0.25-100 ng/mL for asenapine and iloperidone; 2.5-1000 ng/mL for amisulpride, aripiprazole, vilazodone and zotepine; 2.3-924.6 ng/mL for dehydroaripiprazole; 2.2-878.4 ng/mL for melperone; and 2.2-883.5 ng/mL for ziprasidone. Limits of quantitation below a therapeutic reference range were achieved for all analytes. Intra-run precision of 0.4-5.5 %, inter-run precision of 0.6-8.2% and overall recovery of 87.9-114.1% were obtained. The validated method was successfully implemented into routine practice for therapeutic drug monitoring in our hospital.

Experimental implementation of optimal linear-optical controlled-unitary gates.

We show that it is possible to reduce the number of two-qubit gates needed for the construction of an arbitrary controlled-unitary transformation by up to 2 times using a tunable controlled-phase gate. On the platform of linear optics, where two-qubit gates can only be achieved probabilistically, our method significantly reduces the amount of components and increases success probability of a two-qubit gate. The experimental implementation of our technique presented in this Letter for a controlled single-qubit unitary gate demonstrates that only one tunable controlled-phase gate is needed instead of two standard controlled-not gates. Thus, not only do we increase the success probability by about 1 order of magnitude (with the same resources), but also avoid the need for conducting quantum nondemolition measurement otherwise required to join two probabilistic gates. Subsequently, we generalize our method to a higher order, showing that n-times controlled gates can be optimized by replacing blocks of controlled-not gates with tunable controlled-phase gates.

Lateral resolution in NALDI MSI: back to the future.

Nanostructure-assisted laser desorption/ionization (NALDI) has been recognized as a powerful matrix-free mass spectrometry tool ideal for imaging of small molecules. In this report, the NALDI approach was compared with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry in terms of sensitivity, reproducibility, and lateral resolution, which can be achieved in mass spectrometry imaging (MSI) experiments using a Nd:YAG laser. Scanning electron microscopy was used for surface topology analysis and evaluation of a putative surface-enhanced sensitivity effect, which was observed upon reduction of the laser focus. NALDI was identified as a more reproducible technique lacking MSI artifacts arising from distant tissue removal known from MALDI oversampling.

Fabry disease: renal sphingolipid distribution in the α-Gal A knockout mouse model by mass spectrometric and immunohistochemical imaging.

Fabry disease is an X-linked lysosomal storage disease due to deficient α-galactosidase A (α-Gal A) activity and the resultant lysosomal accumulation of globotriaosylceramide (Gb3) and related lipids primarily in blood vessels, kidney, heart, and other organs. The renal distribution of stored glycolipid species in the α-Gal A knockout mouse model was compared to that in mice to assess relative distribution and absolute amounts of accumulated sphingolipid isoforms. Twenty isoforms of five sphingolipid groups were visualized by mass spectrometry imaging (MSI), and their distribution was compared with immunohistochemical (IHC) staining of Gb3, the major stored glycosphingolipid in consecutive tissue sections. Quantitative bulk lipid analysis of tissue sections was assessed by electrospray ionization with tandem mass spectrometry (ESI-MS/MS). In contrast to the findings in wild-type mice, all three analytical techniques (MSI, IHC, and ESI-MS/MS) revealed increases in Gb3 isoforms and ceramide dihexosides (composed mostly of galabiosylceramides), respectively. To our knowledge, this is the first report of the distribution of individual molecular species of Gb3 and galabiosylceramides in kidney sections in Fabry disease mouse. In addition, the spatial distribution of ceramides, ceramide monohexosides, and sphingomyelin forms in renal tissue is presented and discussed in the context of their biosynthesis.

Characterization of natural organic colorants in historical and art objects by high-performance liquid chromatography.

High-performance liquid chromatography plays an important role in analysis of historical organic colorants. A number of papers have been published in this field over the last 30 years. Classification of the most commonly used natural dyes and an overview of high-performance liquid chromatography methods with main focus on recent works (2008 to the beginning of 2014) are provided. The review deals with an entire analytical protocol covering sample preparation, chromatographic separation, and suitable detection (UV/visible and fluorescent spectroscopy and mass spectrometric techniques). High-performance liquid chromatography has been successfully used in the complete characterization of some organic dyestuffs present in historical and art objects. The possibilities and difficulties for identification of natural sources of historical colorants are also discussed.

Aspects of trapping efficiency and matrix effects in the development of a restricted-access-media-based trap-and-elute liquid chromatography with mass spectrometry method.

Online restricted access media with liquid chromatography and tandem mass spectrometry for the direct analysis of small molecules in biological fluids represents an interesting alternative to time-demanding traditional sample preparation techniques. In this study, important considerations concerning the development of a restricted access media with liquid chromatography and tandem mass spectrometry method for the analysis of dansylated estrogens in biological matrix are presented. Parameters influencing peak tailing and trapping efficiency were evaluated. The key factors included the ion strength of the mobile phase, a loading flow rate of the sample onto the trap column, and selection of a proper stationary phase of the trap column for a given set of analytes. These parameters have proven to be essential for minimizing any unwanted chromatographic peak tailing. The bulk derivatization of the analytes in the biological fluids and its relationship to the observed matrix effects was evaluated as well.