Analytical and Bioanalytical Chemistry (v.409, #13)

is a research fellow at the Laboratorio Arvedi di Diagnostica Non Invasiva, University of Pavia, Italy. She graduated in Science for Conservation and Restoration (master’s degree, 2012) studying the glassy matrix and the crystalline inclusions of Roman glass mosaic tesserae using different techniques, including Raman spectroscopy and SEM-EDX. Since 2013, her research has focused on the characterization of ancient musical instruments by means of non-invasive diagnostic methodologies and she has specialized in reflection FT-IR spectroscopy (ATR-IR, total reflection, transflection). is a researcher at Laboratorio di Diagnostica per i Beni Culturali di Spoleto (Italy). Her Ph.D. degree in Chemistry at the University of Perugia focused on the reflection infrared spectroscopy for the study of painting materials. Besides being an expert in FTIR spectroscopy, her research interests include analysis of cultural heritage by means of non-invasive techniques particularly multispectral imaging. is a researcher at Laboratorio di Diagnostica per i Beni Culturali di Spoleto (Italy). She obtained her Ph.D. degree in Chemistry at the University of Perugia in with a thesis titled “Study of painting materials: novel analytical strategies for the identification of organic compounds and alteration products.” Her research interests include identification of painting materials by X-ray fluorescence and diffractometry, vibrational and electronic spectroscopies (Raman, NIR and MID-FTIR, VIS-reflectance), and biomolecular techniques. is a researcher of University of Pavia specialized in chemistry of art works conservation and restoration. Since 2012, he is the scientific manager of the Arvedi Laboratory for non-invasive diagnostics in the Museum of the Violin in Cremona (Italy). Malagodi has been the scientific head of several research projects and actually is a permanent member of the Scientific Committee of Museum of Violin. The analysis of historical musical instruments is becoming more relevant and the interest is increasingly moving toward the non-invasive reflection FTIR spectroscopy, especially for the analysis of varnishes. In this work, a specific infrared reflectance spectral library of organic compounds was created with the aim of identifying musical instrument materials in a totally non-invasive way. The analyses were carried out on pure organic compounds, as bulk samples and laboratory wooden models, to evaluate the diagnostic reflection mid-infrared (MIR) bands of proteins, polysaccharides, lipids, and resins by comparing reflection spectra before and after the KK correction. This methodological approach was applied to real case studies represented by four Stradivari violins and a Neapolitan mandolin.
Keywords: Reflection infrared spectroscopy; Mid-FTIR; Organic materials; Stringed musical instruments; Violins; Varnishes

Assessment of nucleosides as putative tumor biomarkers in prostate cancer screening by CE–UV by Adriana Zardini Buzatto; Mariana de Oliveira Silva; Ronei Jesus Poppi; Ana Valéria Colnaghi Simionato (3289-3297).
received her M.Sc. degree in analytical chemistry from the University of Campinas, Brazil, for the development of a method for the analysis of putative prostate cancer biomarkers. She has also worked on the metabolomics of non-Hodgkin’s lymphoma using chromatography and mass spectrometry. Currently, she is a Ph.D. student at the University of Alberta, Canada, and is particularly interested in the metabolomics and lipidomics of biological fluids using liquid chromatography–mass spectrometry. is an undergraduate student at Institute of Chemistry, University of Campinas, Brazil. She participated in a research project in metabolomics leaded by Ana Valéria Colnaghi Simionato. In the fifth and sixth undergraduate semesters, she went to the University of Bristol, UK, where she studied and obtained experience with soft matter in Wuge Briscoe’s group. is Full Professor at Institute of Chemistry, University of Campinas, Brazil, and Head of the Laboratory of Chemometrics in Analytical Chemistry. He is a member of the National Institute of Science and Technology for Bioanalytics. He has been working for several years on the development and application of chemometric tools, such as pattern recognition, multivariate calibration, multivariate curve resolution and multiway analysis, for data treatment of instrumental analytical techniques, mainly near-infrared spectroscopy, Raman spectroscopy, and chromatography. is Associate Professor at Institute of Chemistry, University of Campinas, Brazil, and Head of the Laboratory of Analysis of Biomolecules Tiselius. She is a member of the National Institute of Science and Technology for Bioanalytics, a member of the Scientific Committee of the Latin American Symposium on Biotechnology, Biomedical, Biopharmaceutical, and Industrial Applications of Capillary Electrophoresis and Microchip Technology, and a member of the Scientific Committee of the Brazilian Society for Mass Spectrometry. She works with separation techniques (capillary electrophoresis, liquid chromatography, and gas chromatography) and mass spectrometry mainly dedicated to metabolomic studies of human disease biomarkers and medicine residues in meat. Cancer is responsible for millions of deaths worldwide, but most base diseases may be cured if detected early. Screening tests may be used to identify early-stage malignant neoplasms. However, the major screening tool for prostate cancer, the prostate-specific antigen test, has unsuitable sensitivity. Since cancer cells may affect the pattern of consumption and excretion of nucleosides, such biomolecules are putative biomarkers that can be used for diagnosis and treatment evaluation. Using a previously validated method for the analysis of nucleosides in blood serum by capillary electrophoresis with UV–vis spectroscopy detection, we investigated 60 samples from healthy individuals and 42 samples from prostate cancer patients. The concentrations of nucleosides in both groups were compared and a multivariate partial least squares–discriminant analysis classification model was optimized for prediction of prostate cancer. The validation of the model with an independent sample set resulted in the correct classification of 82.4% of the samples, with sensitivity of 90.5% and specificity of 76.7%. A significant downregulation of 5-methyluridine and inosine was observed, which can be indicative of the carcinogenic process. Therefore, such analytes are potential candidates for prostate cancer screening. Graphical Abstract Separation of the studied nucleosides and the internal standard 8-Bromoguanosine by CE-UV (a); classification of the external validation samples (30 from healthy volunteers and 21 from prostate cancer patients) by the developed Partial Least Square – Discriminant Analysis (PLS-DA) model with accuracy of 82.4% (b); Receiver Operating Characteristics (ROC) curve (c); and Variable Importance in the Projection (VIP) values for the studied nucleosides (d). A significant down-regulation of 5- methyluridine (5mU) and inosine (I) was observed, which can be indicative of the presence of prostate tumors.
Keywords: Blood serum; Micellar electrokinetic capillary chromatography,·Tumor biomarker; Nucleosides; Target metabolome; Prostate cancer; Carcinogenesis

A hybrid LIBS–Raman system combined with chemometrics: an efficient tool for plastic identification and sorting by K. M. Muhammed Shameem; Khoobaram S. Choudhari; Aseefhali Bankapur; Suresh D. Kulkarni; V. K. Unnikrishnan; Sajan D. George; V. B. Kartha; C. Santhosh (3299-3308).
Classification of plastics is of great importance in the recycling industry as the littering of plastic wastes increases day by day as a result of its extensive use. In this paper, we demonstrate the efficacy of a combined laser-induced breakdown spectroscopy (LIBS)–Raman system for the rapid identification and classification of post-consumer plastics. The atomic information and molecular information of polyethylene terephthalate, polyethylene, polypropylene, and polystyrene were studied using plasma emission spectra and scattered signal obtained in the LIBS and Raman technique, respectively. The collected spectral features of the samples were analyzed using statistical tools (principal component analysis, Mahalanobis distance) to categorize the plastics. The analyses of the data clearly show that elemental information and molecular information obtained from these techniques are efficient for classification of plastics. In addition, the molecular information collected via Raman spectroscopy exhibits clearly distinct features for the transparent plastics (100% discrimination), whereas the LIBS technique shows better spectral feature differences for the colored samples. The study shows that the information obtained from these complementary techniques allows the complete classification of the plastic samples, irrespective of the color or additives. This work further throws some light on the fact that the potential limitations of any of these techniques for sample identification can be overcome by the complementarity of these two techniques. Graphical Abstract ᅟ
Keywords: Laser ablation; Raman spectroscopy; Chemometrics; Complementarity; Polymers

As one of the most important posttranslational modifications, protein phosphorylation plays an important role in vital movement. However, an efficiency enrichment treatment prior to MS detection is still a crucial step to protein phosphorylation analysis. In this work, a novel hybrid microsphere for efficient phosphopeptide enrichment was prepared by reverse-phase suspension polymerization of cellulose derivative and chitosan. The microspheres bore different kinds of amine groups and the main enrichment mechanism was based on anion exchange. This approach exhibited high selectivity for phosphopeptides from β-casein, α-casein, and non-fat milk. Three phosphopeptides could still be detected when the amount of β-casein was as low as 10 fmol. This study demonstrated a new attractive solid-phase support for phosphopeptide enrichment to meet the increasing need of phosphoproteomics analysis.
Keywords: Phosphopeptide; Mass spectrometry; Cellulose; Chitosan; Quaternization

A fast and reliable spectroscopic method for multicomponent quantitative analysis of targeted compounds with overlapping signals in complex mixtures has been established. The innovative analytical approach is based on the preliminary chemometric extraction of qualitative and quantitative information from UV–vis and IR spectral profiles of a calibration system using independent component analysis (ICA). Using this quantitative model and ICA resolution results of spectral profiling of “unknown” model mixtures, the absolute analyte concentrations in multicomponent mixtures and authentic samples were then calculated without reference solutions. Good recoveries generally between 95% and 105% were obtained. The method can be applied to any spectroscopic data that obey the Beer–Lambert–Bouguer law. The proposed method was tested on analysis of vitamins and caffeine in energy drinks and aromatic hydrocarbons in motor fuel with 10% error. The results demonstrated that the proposed method is a promising tool for rapid simultaneous multicomponent analysis in the case of spectral overlap and the absence/inaccessibility of reference materials.
Keywords: Standardless analysis; Independent component analysis; Absorption spectroscopy; UV–vis; IR spectroscopy

Development of a matrix-based candidate reference material of total homocysteine in human serum by Yu Liu; Dewei Song; Bei Xu; Hongmei Li; Xinhua Dai; Baorong Chen (3329-3335).
We developed and evaluated a candidate serum reference material to help improve clinical routine measurement, and to provide traceability of the measurement results. D8-Homocystine, dithiothreitol, and acetonitrile were used as an internal standard, the reducing agent, and the protein precipitating agent, respectively. A triple quadrupole mass spectrometer with an electrospray ionization source was used for monitoring the transitions (m/z 140.0 → 94.0, 136.0 → 90.0) in multiple-reaction-monitoring mode. We used a calibration model relying on bracketing and gravimetric measurements to give SI-traceability and higher accuracy to serum value assignments. The method was evaluated for accuracy using NIST Standard Reference Material SRM1955. The results of the three concentrations (1, 2, and 3) of total homocysteine in human serum samples were determined by an isotope-dilution liquid chromatography-tandem mass spectrometry method; tHcy 1 is 28.8 ± 1.1 μmol/L, tHcy 2 is 17.93 ± 0.57 μmol/L, and tHcy 3 is 14.38 ± 0.46 μmol/L. Graphical abstract The workflow diagram.
Keywords: Homocysteine; Human serum; Reference material; Isotope dilution mass spectrometry

Alkyl moieties which can retain target analytes due to their lipophilicity are important in sample preparation. In this work, hexadecyl-functionalized magnetic core-shell microspheres (Fe3O4@SiO2-C16) was successfully prepared by one-pot sol–gel method and used for magnetic solid-phase extraction of polychlorinated biphenyls (PCBs) in environmental water samples. Optimized preparation method was achieved by altering the adding moment of hexadecyl-silane. The resultant materials were systematically characterized by scanning electron microscope, transmission electron microscope, Fourier transform infrared spectroscopy, energy dispersive X-ray spectrometry, tensionmeter, and vibrating sample magnetometer. The results demonstrated that the optimized adsorbent exhibited core-shell structure, superparamagnetic (66 emu/g), and extremely hydrophobic (water contact angle of 122°) properties. To evaluate the extraction performance, the prepared material coupled with gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) was applied to determinate PCBs. The extraction conditions were optimized. Under the optimal conditions, the proposed method showed a good linearity range of 1–100 ng L−1 with correlation coefficients (R) of 0.9989–0.9993. Based on a signal-to-noise ratio of 3 and 10, the limits of detection (LODs) and limits of quantification (LOQs) were in the range 0.14–0.27 and 0.39–0.91 ng L−1, respectively. The intra- and inter-day relative standard deviations (RSDs) were less than 9.06%. The absolute recoveries of PCBs in spiked real water samples were in the range of 75.17 to 101.20%. Additionally, reusability and batch-to-batch reproducibility of the resultant material were acceptable with RSDs less than 5.64 and 3.25%, respectively. Graphical Abstract The synthesis procedure of Fe3O4@SiO2-C16 and determination of PCBs in water sample 129 × 50 mm (300 × 300 DPI)
Keywords: Hexadecyl; Magnetic microsphere; Polychlorinated biphenyl; Gas chromatography-tandem mass spectrometry; Water

Analytical strategy for determination of known and unknown destruxins using hybrid quadrupole-Orbitrap high-resolution mass spectrometry by Natalia Arroyo-Manzanares; José Diana Di Mavungu; Inmaculada Garrido-Jurado; Lourdes Arce; Lynn Vanhaecke; Enrique Quesada-Moraga; Sarah De Saeger (3347-3357).
An analytical strategy based on a hybrid quadrupole-Orbitrap mass spectrometry was proposed for the simultaneous screening of known destruxins and characterization of potential members of this class of secondary metabolites, in order to evaluate the metabolite production of entomopathogenic fungi used as biocontrol agents. Initially, the fragmentation pathway of the known and commercially available destruxin A was established combining high resolution mass spectrometry (HRMS) and multiple stage MS data in order to obtain the strategy for the characterization of other destruxins for which reference standards were not available. Nineteen known destruxins including A, B, C, D, Ed, F, A1, B1, Ed1, A2, B2, D2, A3, DesmA, DesmB, DesmC, DesmB2, and two chloro-derivatives (Cl and E2 chlorohydrin) were unequivocally identified in Metarhizium brunneum using the proposed strategy. In addition, four unknown destruxins, namely C1, Ed2, G, and G1, were structurally elucidated and characterized for the first time in this fungal strain.
Keywords: Destruxins identification; Untargeted analysis; Hybrid quadrupole-Orbitrap; Fragmentation pathway

An automated method is presented for fast simulation of (bio)transformation products (TPs) of the organophosphate insecticide chlorpyrifos (CPF) based on electrochemistry coupled online to liquid chromatography-mass spectrometry (EC-LC-MS). Oxidative TPs were produced by a boron doped diamond (BDD) electrode, separated by reversed phase HPLC and online detected by electrospray ionization-mass spectrometry (ESI-MS). Furthermore, EC oxidative TPs were investigated by HPLC-tandem mass spectrometry (LC-MS/MS) and FT-ICR high resolution mass spectrometry (HRMS) and compared to in vitro assay metabolites (rat and human liver microsomes). Main phase I metabolites of CPF: chlorpyrifos oxon (CPF oxon), trichloropyridinol (TCP), diethylthiophosphate (DETP), diethylphosphate (DEP), desethyl chlorpyrifos (De-CPF), and desethyl chlorpyrifos oxon (De-CPF oxon), were successfully identified by the developed EC-LC-MS method. The EC-LC-MS method showed similar metabolites compared to the in vitro assay with possibilities of determining reactive species. Our results reveal that online EC-(LC)-MS brings an advantage on time of analysis by eliminating sample preparation steps and matrix complexity compared to conventional in vivo or in vitro methods.
Keywords: Organophosphate agrochemicals; Electrochemical oxidation; Metabolism; In vitro; EC-LC-MS; LC-MS/MS

Multi-mycotoxin analysis using dried blood spots and dried serum spots by Bernd Osteresch; Susana Viegas; Benedikt Cramer; Hans-Ulrich Humpf (3369-3382).
In this study, a rapid multi-mycotoxin approach was developed for biomonitoring and quantification of 27 important mycotoxins and mycotoxin metabolites in human blood samples. HPLC-MS/MS detection was used for the analysis of dried serum spots (DSS) and dried blood spots (DBS). Detection of aflatoxins (AFB1, AFB2, AFG1, AFG2, AFM1), trichothecenes (deoxynivalenol, DON; DON-3-glucoronic acid, DON-3-GlcA; T-2; HT-2; and HT-2-4-GlcA), fumonisin B1 (FB1), ochratoxins (OTA and its thermal degradation product 2’R-OTA; OTα; 10-hydroxychratoxin A, 10-OH-OTA), citrinin (CIT and its urinary metabolite dihydrocitrinone, DH-CIT), zearalenone and zearalanone (ZEN, ZAN), altenuene (ALT), alternariols (AOH; alternariol monomethyl ether, AME), enniatins (EnA, EnA1, EnB, EnB1) and beauvericin (Bea) was validated for two matrices, serum (DSS), and whole blood (DBS). HPLC-MS/MS analysis showed signal suppression as well as signal enhancement due to matrix effects. However, for most analytes LOQs in the lower pg/mL range and excellent recovery rate were achieved using matrix-matched calibration. Besides validation of the method, the analyte stability in DBS and DSS was also investigated. Stability is a main issue for some analytes when the dried samples are stored under common conditions at room temperature. Nevertheless, the developed method was applied to DBS samples of a German cohort (n = 50). Besides positive findings of OTA and 2’R-OTA, all samples were positive for EnB. This methodical study establishes a validated multi-mycotoxin approach for the detection of 27 mycotoxins and metabolites in dried blood/serum spots based on a fast sample preparation followed by sensitive HPLC-MS/MS analysis. Graphical Abstract ᅟ
Keywords: Biomonitoring; Dried blood spot; Dried serum spot; HPLC-MS/MS; Mass spectrometry; Mycotoxin

The combination of dried blood spots (DBS) and bottom-up LC-MS-based protein analysis was investigated in the present paper using six model proteins (1 mg/mL of each protein) with different physicochemical properties. Two different materials for DBS were examined: a water-soluble DBS material (carboxymethyl cellulose, (CMC)) and a commercially available (non-soluble) material (DMPK-C). The sample preparation was optimised regarding the water-soluble material and achieving acceptable repeatability of the signal was emphasised. Five microlitres of whole blood were deposited and dried on either CMC or DMPK-C. The samples were dissolved (CMC) or extracted (DMPK-C) prior to tryptic digest and matrix precipitation. The optimization of the sample preparation showed that an increased buffer concentration (100 mM ammonium bicarbonate) for dissolving the DBS samples gave better repeatability combined with a decrease in analyte signal. CMC seemed to add extra variability (RSD 8–60%) into the analysis compared to sample prepared without CMC (RSD 6–36%), although equal performance compared to DMPK-C material (RSD 13–60%) was demonstrated. The stability of the analytes was examined for different storage periods (1 and 4 weeks) and different storage temperatures (−25, 25, and 40 °C). The stability on both CMC (> 70% compared to reference) and DMPK-C (> 50% compared to reference) was acceptable for most of the peptides. This paper shows that both DBS materials can be used in targeted LC-MS-based protein analysis of proteins with different physicochemical properties. Graphical Abstract Overview of the experimental set-up for expanding the knowledge of dried blood spots in LC-MS-based protein anaysis
Keywords: LC-MS; Protein analysis; Bottom-up; Dried blood spots (DBS)

Molecularly imprinted polymers as selective adsorbents for ambient plasma mass spectrometry by Michał Cegłowski; Marek Smoluch; Edward Reszke; Jerzy Silberring; Grzegorz Schroeder (3393-3405).
The application of molecularly imprinted polymers (MIPs) as molecular scavengers for ambient plasma ionization mass spectrometry has been reported for the first time. MIPs were synthesized using methacrylic acid as functional monomer; nicotine, propyphenazone, or methylparaben as templates; ethylene glycol dimethacrylate as a cross-linker; and 2,2′-azobisisobutyronitrile as polymerization initiator. To perform ambient plasma ionization experiments, a setup consisting of the heated crucible, a flowing atmospheric-pressure afterglow (FAPA) plasma ion source, and a quadrupole ion trap mass spectrometer has been used. The heated crucible with programmable temperature allows for desorption of the analytes from MIPs structure which results in their direct introduction into the ion stream. Limits of detection, linearity of the proposed analytical procedure, and selectivities have been determined for three analytes: nicotine, propyphenazone, and methylparaben. The analytes used were chosen from various classes of organic compounds to show the feasibility of the analytical procedure. The limits of detections (LODs) were 10 nM, 10, and 0.5 μM for nicotine, propyphenazone, and methylparaben, respectively. In comparison with the measurements performed for the non-imprinted polymers, the values of LODs were improved for at least one order of magnitude due to preconcentration of the sample and reduction of background noise, contributing to signal suppression. The described procedure has shown linearity in a broad range of concentrations. The overall time of single analysis is short and requires ca. 5 min. The developed technique was applied for the determination of nicotine, propyphenazone, and methylparaben in spiked real-life samples, with recovery of 94.6–98.4%. The proposed method is rapid, sensitive, and accurate which provides a new option for the detection of small organic compounds in various samples. Graphical abstract The experimental setup used for analysis
Keywords: Molecularly imprinted polymers; Ambient plasma mass spectrometry; Selective adsorption; Molecular scavengers; Flowing atmospheric pressure afterglow

Thyrotropin or thyroid-stimulating hormone (TSH) is used as a marker for thyroid function. More precise and more sensitive immunoassays are needed to facilitate continuous monitoring of thyroid dysfunctions and to assess the efficacy of the selected therapy and dosage of medication. Moreover, most thyroid diseases are autoimmune diseases making TSH assays very prone to immunoassay interferences due to autoantibodies in the sample matrix. We have developed a super-sensitive TSH immunoassay utilizing nanoparticle labels with a detection limit of 60 nU L−1 in preprocessed serum samples by reducing nonspecific binding. The developed preprocessing step by affinity purification removed interfering compounds and improved the recovery of spiked TSH from serum. The sensitivity enhancement was achieved by stabilization of the protein corona of the nanoparticle bioconjugates and a spot-coated configuration of the active solid-phase that reduced sedimentation of the nanoparticle bioconjugates and their contact time with antibody-coated solid phase, thus making use of the higher association rate of specific binding due to high avidity nanoparticle bioconjugates. Graphical Abstract We were able to decrease the lowest limit of detection and increase sensitivity of TSH immunoassay using Eu(III)-nanoparticles. The improvement was achieved by decreasing binding time of nanoparticle bioconjugates by small capture area and fast circular rotation. Also, we applied a step to stabilize protein corona of the nanoparticles and a serum-preprocessing step with a structurally related antibody.
Keywords: Sandwich-type immunoassay; Time-resolved fluoroimmunoassay; Nanoparticle bioconjugate; Immunoassay interference; Nanoparticle protein corona

Thiols (-SH) play various roles in biological systems. They are divided into protein thiols (PSH) and non-protein thiols (NPSH). Due to the significant roles thiols play in various physiological/pathological functions, numerous analytical methods have been developed for thiol assays. Most of these methods are developed for glutathione, the major form of NPSH. Majority of these methods require tissue/cell homogenization before analysis. Due to a lack of effective thiol-specific fluorescent/fluorogenic reagents, methods for imaging and quantifying thiols in live cells are limited. Determination of an analyte in live cells can reveal information that cannot be revealed by analysis of cell homogenates. Previously, we reported a thiol-specific thiol-sulfide exchange reaction. Based on this reaction, a benzofurazan sulfide thiol-specific fluorogenic reagent was developed. The reagent was able to effectively image and quantify total thiols (PSH+NPSH) in live cells through fluorescence microscopy. The reagent was later named as GUALY’s reagent. Here we would like to report an extension of the work by synthesizing a novel benzofurazan sulfide triphenylphosphonium derivative [(((7,7′-thiobis(benzo[c][1,2,5]oxadiazole-4,4′-sulfonyl))bis(methylazanediyl))bis(butane-4,1-diyl))bis(triphenylphosphonium) (TBOP)]. Like GUALY’s reagent, TBOP is a thiol-specific fluorogenic agent that is non-fluorescent but forms fluorescent thiol adducts in a thiol-specific fashion. Different than GUALY’s reagent, TBOP reacts only with NPSH but not with PSH. TBOP was effectively used to image and quantify NPSH in live cells using fluorescence microscopy. TBOP is a complementary reagent to GUALY’s reagent in determining the roles of PSH, NPSH, and total thiols in thiol-related physiological/pathological functions in live cells through fluorescence microscopy. Graphical Abstract Live cell imaging and quantification of non-protein thiols by TBOP
Keywords: Non-protein thiol; Thiol-specific fluorogenic agent; Live cell thiol imaging; Fluorescence microscopy

Covalent organic frameworks as a novel fiber coating for solid-phase microextraction of volatile benzene homologues by Shuaihua Zhang; Qian Yang; Zhi Li; Wenchang Wang; Chun Wang; Zhi Wang (3429-3439).
Covalent organic frameworks (COFs) have attracted great research interest due to their fascinating structures and potential applications in various fields. Here, the COF-SCU1 (SCU for Sichuan University) coated solid-phase microextraction (SPME) fibers were fabricated by coating it on prior functionalized stainless steel wires via a simple physical coating method, and applied to extract some volatile benzene homologues from indoor air samples. The main experimental parameters affecting the extraction efficiency were optimized, including extraction temperature, extraction time, and desorption time. The developed method, which combined the COF-SCU1 coated fiber-based SPME with gas chromatography-mass spectrometric detection, gave large enrichment factors (276–887), low limits of detection (0.03–0.15 ng L−1), and good linearity (0.10–20 ng L−1) for the determination of gaseous benzene homologues from three different indoor air samples. The precision (expressed as the relative standard deviations, RSDs) for six replicate determinations of the analytes at 10 ng L−1 each of the analytes using the same COF-SCU1 coated fiber ranged from 5.8 to 8.9%. The fiber-to-fiber reproducibility for three parallel COF-SCU1 coated fibers varied from 6.9 to 10.7%. The recoveries of the analytes for the method for the spiked indoor air samples with the benzene homologues at the two concentrations of 1 and 10 ng L−1 were in the range of 88.6–101.5% and 87.9–103.4% with the RSDs ranging from 3.9 to 10.3% and 3.4 to 8.5%, respectively. Graphical Abstract The covalent organic frameworks were applied as a novel fiber coating material for the solid-phase microextraction of volatile benzene homologues.
Keywords: Covalent organic frameworks; Solid-phase microextraction; Benzene homologues; Indoor air samples

Chemical degradation is an efficient method to obtain bio-oils and other compounds from lignin. Lignin bio-oils are potential substitutes for the phenol component of phenol formaldehyde (PF) resins. Here, we developed an analytical method based on high resolution mass spectrometry that provided structural information for the synthesized lignin-derived resins and supported the prediction of their properties. Different model resins based on typical lignin degradation products were analyzed by electrospray ionization in negative ionization mode. Utilizing enhanced mass defect filter techniques provided detailed structural information of the lignin-based model resins and readily complemented the analytical data from differential scanning calorimetry and thermogravimetric analysis. Relative reactivity and chemical diversity of the phenol substitutes were significant determinants of the outcome of the PF resin synthesis and thus controlled the areas of application of the resulting polymers. Graphical abstract ᅟ
Keywords: Bio-oils; Lignin; High resolution mass spectrometry; Mass defect; Phenol formaldehyde resin

A novel three-dimensional (3D) magnetic imprinted polymer was prepared with bovine serum albumin as the template molecule, dopamine as the functional monomer, and a graphene oxide and carbon nanotube hybrid 3D nanocomposite as the carrier. The preparation conditions for the 3D magnetic molecularly imprinted polymers were optimized. The 3D magnetic molecularly imprinted polymers were characterized in detail by scanning electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. The 3D magnetic molecularly imprinted polymers possessed a fast adsorption rate and excellent adsorption performance toward bovine serum albumin, with a maximum adsorption capacity of 78.12 mg g-1. The extraction conditions, including the washing solvent, the pH of the eluent, and the desorption time, were also optimized. Combined with high-performance liquid chromatography, the 3D magnetic molecularly imprinted polymers were successfully applied to enrich and separate bovine serum albumin from bovine calf serum samples with recoveries of 84.0–94.5%. Graphical Abstract ᅟ
Keywords: 3D magnetic molecularly imprinted polymers; Bovine serum albumin; Magnetic solid-phase extraction; Graphene oxide; Carbon nanotubes

Chlorinated polycyclic aromatic hydrocarbons (ClPAHs), including polychlorinated naphthalenes (PCNs), are hazardous and widespread in the environment, but studies of these substances in the wastewater environment are lacking. In this study, five typical PCNs and five typical ClPAHs (other than PCNs) were simultaneously detected along with their parent polycyclic aromatic hydrocarbons in wastewater samples. All these compounds could be analyzed by gas chromatography– electron ionization mass spectrometry in selected ion monitoring mode and separated on a DB-17ms column. Calibration curves were created both in pure solvent and in wastewater matrix samples. The coefficients of determination for most compounds were greater than 0.99, indicating a satisfactory degree of linearity in the complex matrix samples. The influence of the matrix on the true concentrations of the environmental samples was corrected by use of the matrix calibration curve. The recoveries of all compounds were between 58% and 127%, with standard deviations lower than 20%. The method detection and quantification limits were less than 27.6 ng/L and less than 91.9 ng/L respectively in the aqueous phase, and less than 0.18 ng/L and less than 0.61 ng/L respectively in the solid phase of 4-L wastewater samples. This analytical method was successfully used to detect PCNs and ClPAHs in the water from a river receiving effluent from a wastewater treatment plant. The concentrations of each compound ranged from 3.1 to 29.6 ng/L. This method could also be used for detection of other polycyclic aromatic hydrocarbon derivatives with similar physical and chemical properties in different matrix samples. Graphical Abstract ᅟ
Keywords: Chlorinated polycyclic aromatic hydrocarbons; Polychlorinated naphthalenes; Solid-phase extraction; Accelerated solvent extraction; Water matrix

Measuring transdermal glucose levels in neonates by passive diffusion: an in vitro porcine skin model by Cristina Tiangco; Abhay Andar; Juliana Quarterman; Xudong Ge; Fortunato Sevilla III; Govind Rao; Audra Stinchcomb; Annette Bunge; Leah Tolosa (3475-3482).
Current glucose monitoring techniques for neonates rely heavily on blood glucose monitors which require intermittent blood collection through skin-penetrating pricks on the heel or fingers. This procedure is painful and often not clinically conducive, which presents a need for a noninvasive method for monitoring glucose in neonates. Our motivation for this study was to develop an in vitro method for measuring passive diffusion of glucose in premature neonatal skin using a porcine skin model. Such a model will allow us to initially test new devices for noninvasive glucose monitoring without having to do in vivo testing of newborns. The in vitro model is demonstrated by comparing uncompromised and tape-stripped skin in an in-line flow-through diffusion apparatus with glucose concentrations that mimic the hypo-, normo-, and hyper-glycemic conditions in the neonate (2.0, 5.0, and 20 mM, respectively). Transepidermal water loss (TEWL) of the tape-stripped skin was approximately 20 g m−2 h−1, which closely mimics TEWL for neonatal skin at about 190 days post-conceptional age. The tape-stripped skin showed a >15-fold increase in glucose diffusion compared to the uncompromised skin. The very small concentrations of collected glucose were measured with a highly selective and highly sensitive fluorescent glucose biosensor based on the glucose binding protein (GBP). The demonstrated method of glucose determination is noninvasive and painless, which makes it especially desirable for glucose testing in neonates and children. This study is an important step towards an in vitro model for noninvasive real-time glucose monitoring that may be easily transferred to the clinic for glucose monitoring in neonates. Graphical Abstract Glucose diffusion through model skin was measured using an in-line flow-through diffusion apparatus with glucose solutions mimicking hypo-, normo- and hyperglycemia in the neonate. Phosphate buffered saline was added to the top chamber and the glucose that diffused through the model skin into the buffer was measured using a fluorescent glucose binding protein biosensor.
Keywords: Biosensors; Bioassays; In-line flow-through diffusion cell; Passive diffusion; Transdermal glucose monitoring; Neonates

Development of certified reference materials for electrolytes in human serum (GBW09124-09126) by Liuxing Feng; Jun Wang; Yanjie Cui; Naijie Shi; Haifeng Li; Hongmei Li (3483-3493).
Three reference materials, at relatively low, middle, and high concentrations, were developed for analysis of the mass fractions of electrolytes (K, Ca, Na, Mg, Cl, and Li) in human serum. The reference materials were prepared by adding high purity chloride salts to normal human serum. The concentration range of the three levels is within ±20% of normal human serum. It was shown that 14 units with duplicate analysis is enough to demonstrate the homogeneity of these candidate reference materials. The statistical results also showed no significant trends in both short-term stability test for 1 week at 40 °C and long-term stability test for 14 months. The certification methods of the six elements include isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS), inductively coupled plasma optical emission spectroscopy (ICP-OES), atomic absorption spectroscopy (AAS), ion chromatography (IC), and ion-selective electrode (ISE). The certification methods were validated by international comparisons among a number of national metrology institutes (NMIs). The combined relative standard uncertainties of the property values were estimated by considering the uncertainties of the analytical methods, homogeneity, and stability. The range of the expanded uncertainties of all the elements is from 2.2% to 3.9%. The certified reference materials (CRMs) are primarily intended for use in the calibration and validation of procedures in clinical analysis for the determination of electrolytes in human serum or plasma. Graphical Abstract Certified reference materials for K, Ca, Mg, Na, Cl and Li in human serum (GBW09124-09126)
Keywords: Certified reference material; Electrolytes; Human serum; International comparison