bims-metlip Biomed News
on Methods and protocols in metabolomics and lipidomics
Issue of 2022–04–10
forty-five papers selected by
Sofia Costa, Icahn School of Medicine at Mount Sinai
  1. Reference materials for MS-based untargeted metabolomics and lipidomics: a review by the metabolomics quality assurance and quality control consortium (mQACC).
  2. Metabolomic Workflow for the Accurate and High-Throughput Exploration of the Pathways of Tryptophan, Tyrosine, Phenylalanine, and Branched-Chain Amino Acids in Human Biofluids.
  3. Determination of 15 human pharmaceutical residues in fish and shrimp tissues by high-performance liquid chromatography-tandem mass spectrometry.
  4. Ultrasound-assisted micellar cleanup coupled with large-volume-injection enrichment for the analysis of polar drugs in blood and zebrafish samples.
  5. Cyclophosphamide, hydroxycyclophosphamide and carboxyethyl phosphoramide mustard quantification with liquid chromatography mass spectrometry in a single run human plasma samples: A rapid and sensitive method development.
  6. Separation of isomers using a differential mobility analyser (DMA): Comparison of experimental vs modelled ion mobility.
  7. Simultaneous determination of clopidogrel, 2-oxo-clopidogrel, and the thiol metabolite of clopidogrel in human plasma by LC-MS/MS.
  8. Simultaneous Determination of Fifteen Polyphenols in Fruit Juice Using Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry Combining Dispersive Liquid-Liquid Microextraction.
  9. Development of a Method of Liquid Chromatography Coupled with Tandem Mass Spectrometry for Simultaneous Determination of Linezolid and Tedizolid in Human Plasma.
  10. In Silico Collision Cross Section Calculations to Aid Metabolite Annotation.
  11. Explore potential disease related metabolites based on latent factor model.
  12. Are Mass Spectrometry Imaging-Based Diagnostics Becoming Reality?
  13. Adding a diazo-transfer reagent to culture to generate secondary metabolite probes for click chemistry.
  14. Fluxomics - New Metabolomics Approaches to Monitor Metabolic Pathways.
  15. Open Search of Peptide Glycation Products from Tandem Mass Spectra.
  16. Simultaneous solvent extraction and quantification of eleven amine compounds related to Chemical Weapon Convention in soils via hydrophilic interaction liquid chromatography-tandem mass spectrometry.
  17. Novel carrier-mediated membrane-assisted three-phase liquid-liquid extraction coupled with liquid chromatography-mass spectrometry for the determination of eight biogenic amines in foods.
  18. Determination of selected α-keto acids in dried blood samples using HPLC with fluorescence detection.
  19. High-Sensitivity and High-Throughput Quantification of Everolimus in Human Whole Blood using Ultra-High-Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry.
  20. Bile Acid Detection Techniques and Bile Acid-Related Diseases.
  21. Parallel Operation of Electron Ionization and Chemical Ionization for GC-MS Using a Single TOF Mass Analyzer.
  22. A quantitative method for the simultaneous detection of SR9009 and SR9011 in equine plasma using liquid chromatography-electrospray ionization-tandem mass spectrometry.
  23. A single LC-MS/MS validated method for tulathromycin quantification in plasma, seminal plasma and urine to be applied in a pharmacokinetic study in bull.
  24. A simple preparation step to remove excess liquid lipids in white adipose tissue enabling improved detection of metabolites via MALDI-FTICR imaging MS.
  25. NEWS: The 2022 Metabolomics publication awards.
  26. The emerging role of lipidomics in prediction of diseases.
  27. Carbon quantum dots-functionalized silica stationary phase for pharmaceutical analysis by a green liquid chromatography mode.
  28. Characterisation and traceability of two generations of standard reference material for the measurement of vitamin K1 (phylloquinone) at endogenous concentrations in human plasma and serum.
  29. A validated method for the rapid quantification of melatonin in over-the-counter hypnotics by the atmospheric pressure solid analysis probe (ASAP).
  30. Comparison of three stationary phases in the separation of polyphenyls by liquid chromatography.
  31. Beyond Δ9-tetrahydrocannabinol and cannabidiol: chemical differentiation of cannabis varieties applying targeted and untargeted analysis.
  32. Untargeted metabolomics and proteomics approach using liquid chromatography-Orbitrap high resolution mass spectrometry to detect pork adulteration in Pangasius hypopthalmus meat.
  33. Development and Validation of a Dried Blood Spot Assay Using UHPLC-MS/MS to Identify and Quantify 12 Antihypertensive Drugs and 4 Active Metabolites: Clinical Needs and Analytical Limitations.
  34. Utilizing imaging mass spectrometry to analyze microbial biofilm chemical responses to exogenous compounds.
  35. Establishing a quantitative fluorescence assay for the rapid detection of kynurenine in urine.
  36. Analytical method to monitor contaminants of emerging concern in water and soil samples from a non-conventional wastewater treatment system.
  37. Advanced tuning of the ion management parameters in GC × GC-HRMS using a Fourier transform Orbitrap mass analyzer for pixel-based data handling and multivariate analysis.
  38. Unsupervised Multi-Omics Data Integration Methods: A Comprehensive Review.
  39. Quantification of Ephedrine Substances in Human Urine by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.
  40. Rapid and One-Step Screening of Taxane Compounds by a Two-Dimensional Carbon Microfiber Fractionation System Combined with Tandem Mass Spectrometry.
  41. Alterations in the Plasma Lipidome of Adult Women With Bipolar Disorder: A Mass Spectrometry-Based Lipidomics Research.
  42. Why tandem mass spectrometry for trace analysis: concepts of tandem analytical techniques.
  43. Fundamental and practical aspects of machine learning for the peak picking of biomolecular NMR spectra.
  44. Development and validation of dispersive liquid-liquid microextraction method for the determination of 15 polycyclic aromatic hydrocarbons in 200 Antarctica samples by gas chromatography mass spectrometry.
  45. Quantification of thyroid hormones and analogs by liquid chromatography coupled to mass spectrometry. Preliminary results in athletes and non-athletes serum samples.
  1. Metabolomics. 2022 Apr 09. 18(4): 24
    Reference materials for MS-based untargeted metabolomics and lipidomics: a review by the metabolomics quality assurance and quality control consortium (mQACC).
    Katrice A Lippa, Juan J Aristizabal-Henao, Richard D Beger, John A Bowden, Corey Broeckling, Chris Beecher, W Clay Davis, Warwick B Dunn, Roberto Flores, Royston Goodacre, Gonçalo J Gouveia, Amy C Harms, Thomas Hartung, Christina M Jones, Matthew R Lewis, Ioanna Ntai, Andrew J Percy, Dan Raftery, Tracey B Schock, Jinchun Sun, Georgios Theodoridis, Fariba Tayyari, Federico Torta, Candice Z Ulmer, Ian Wilson, Baljit K Ubhi.
       INTRODUCTION: The metabolomics quality assurance and quality control consortium (mQACC) is enabling the identification, development, prioritization, and promotion of suitable reference materials (RMs) to be used in quality assurance (QA) and quality control (QC) for untargeted metabolomics research.
    OBJECTIVES: This review aims to highlight current RMs, and methodologies used within untargeted metabolomics and lipidomics communities to ensure standardization of results obtained from data analysis, interpretation and cross-study, and cross-laboratory comparisons. The essence of the aims is also applicable to other 'omics areas that generate high dimensional data.
    RESULTS: The potential for game-changing biochemical discoveries through mass spectrometry-based (MS) untargeted metabolomics and lipidomics are predicated on the evolution of more confident qualitative (and eventually quantitative) results from research laboratories. RMs are thus critical QC tools to be able to assure standardization, comparability, repeatability and reproducibility for untargeted data analysis, interpretation, to compare data within and across studies and across multiple laboratories. Standard operating procedures (SOPs) that promote, describe and exemplify the use of RMs will also improve QC for the metabolomics and lipidomics communities.
    CONCLUSIONS: The application of RMs described in this review may significantly improve data quality to support metabolomics and lipidomics research. The continued development and deployment of new RMs, together with interlaboratory studies and educational outreach and training, will further promote sound QA practices in the community.
    Keywords:  Certified reference materials; Internal standards; Lipidomics; Mass spectrometry; Metabolomics; Metabolomics quality assurance and quality control consortium (mQACC); Reference materials; Untargeted analysis
    DOI:  https://doi.org/10.1007/s11306-021-01848-6
  2. J Proteome Res. 2022 Apr 05.
    Metabolomic Workflow for the Accurate and High-Throughput Exploration of the Pathways of Tryptophan, Tyrosine, Phenylalanine, and Branched-Chain Amino Acids in Human Biofluids.
    Andrea Anesi, Kirsten Berding, Gerard Clarke, Catherine Stanton, John F Cryan, Noel Caplice, R Paul Ross, Andrea Doolan, Urska Vrhovsek, Fulvio Mattivi.
      The modulation of host and dietary metabolites by gut microbiota (GM) is important for maintaining correct host physiology and in the onset of various pathologies. An ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the targeted quantitation in human plasma, serum, and urine of 89 metabolites resulting from human-GM cometabolism of dietary essential amino acids tryptophan, tyrosine, and phenylalanine as well as branched-chain amino acids. Ninety-six-well plate hybrid-SPE enables fast clean-up of plasma and serum. Urine was diluted and filtered. A 15 min cycle enabled the acquisition of 96 samples per day, with most of the metabolites stable in aqueous solution for up to 72 h. Calibration curves were specifically optimized to cover expected concentrations in biological fluids, and limits of detection were at the order of ppb. Matrix effects were in acceptable ranges, and analytical recoveries were in general greater than 80%. Inter and intraday precision and accuracy were satisfactory. We demonstrated its application in plasma and urine samples obtained from the same individual in the frame of an interventional study, allowing the quantitation of 51 metabolites. The method could be considered the reference for deciphering changes in human-gut microbial cometabolism in health and disease. Data are available via Metabolights with the identifier MTBLS4399.
    Keywords:  gut microbiota metabolites; host-gut microbiota cometabolism; mass spectrometry; plasma; serum; tryptophan and tyrosine metabolism; urine
    DOI:  https://doi.org/10.1021/acs.jproteome.1c00946
  3. Environ Monit Assess. 2022 Apr 04. 194(5): 325
    Determination of 15 human pharmaceutical residues in fish and shrimp tissues by high-performance liquid chromatography-tandem mass spectrometry.
    Reza Pashaei, Reda Dzingelevičienė, Sajjad Abbasi, Małgorzata Szultka-Młyńska, Boguslaw Buszewski.
      An efficient, reliable, and sensitive multiclass analytical method has been expanded to simultaneously determine 15 human pharmaceutical residues in fish and shrimp tissue samples by ultra-high-performance liquid chromatography-tandem mass spectrometry. The investigated compounds comprise ten classes, namely, analgesic, antibacterial, anticonvulsant, cardiovascular, fluoroquinolones, macrolides, nonsteroidal anti-inflammatory, penicillins, stimulant, and sulfonamide. A simple liquid extraction procedure based on 0.1% formic acid in methanol was developed. Chromatographic conditions were optimized, and mobile phase A was 0.1% ammonium acetate, and mobile phase B was acetonitrile. The mobile phase's gradient program was as follows: 0-2 min, 15% B; 2-5 min, linear to 95% B; 5-10 min, 95% B; and 10-12 min. The limits of detection were from 0.017 to 1.371 μg/kg, while a quantification range was measured from 0.051 to 4.113 μg/kg. Finally, amoxicillin, azithromycin, caffeine, carbamazepine, ciprofloxacin, clarithromycin, diclofenac, erythromycin, furosemide, ibuprofen, ketoprofen, naproxen, sulfamethoxazole, tetracycline, and triclosan were quantifiable in fish and shrimp samples.
    Keywords:  Fish; Liquid chromatography; Mass spectrometry; Pharmaceuticals; Shrimp; Solid-phase extraction
    DOI:  https://doi.org/10.1007/s10661-022-09993-8
  4. Ultrason Sonochem. 2022 Apr;pii: S1350-4177(22)00091-8. [Epub ahead of print]85 105998
    Ultrasound-assisted micellar cleanup coupled with large-volume-injection enrichment for the analysis of polar drugs in blood and zebrafish samples.
    Xiaotong Du, Jiahao Yuan, Hongjie Cao, Li Ye, Ande Ma, Juan Du, Jialiang Pan.
      A novel ultrasound-assisted micellar cleanup strategy (UAMC) coupled with large volume injection (LVI) high performance liquid chromatography (HPLC) method was proposed and successfully applied to the analysis of cefathiamidine in complex biological samples such as whole blood, plasma, serum and even zebrafish, a challenging positive real sample. Based on the micelle-biomacromolecule interaction, the phase-separation feature of surfactant micelles and ultrasound cavitation, UAMC possessed an impressive matrix cleanup capability and could rapidly reach distribution equilibrium (approximately 2 min), which enabled simultaneous sample cleanup and analyte extraction within 8 min. Due to the high cleanup efficiency of UAMC, large volume of pretreated samples could be injected for analysis without peak broadening, impurity interference and column degradation. Thus, online analyte enrichment could be automatically performed to significantly improve method sensitivity by the column-switching LVI-HPLC system, a commercial HPLC system with small modifications. The UAMC-LVI-HPLC method creatively integrated sample cleanup, analyte extraction and on-column enrichment into simple operation. In addition, the UAMC-LVI-HPLC method enabled non-matrix-matched analysis of cefathiamidine in complex biological samples. This feature was helpful to address the problems caused by conventional matrix-matched or internal standard calibration methods, such as matrix bias, increased workload, limited availability of suitable blank matrices and the use of expensive internal standards. The method had low limits of detections (e.g., 0.0051 mg/L and 0.038 μg/g), wide linear ranges (0.030-100 mg/L and 0.15-489 μg/g), good linear correlation (R2 = 0.9999), satisfactory accuracy (97.6-109.7%) and excellent intra- and interday precision (0.5-4.9%). Thus, UAMC-LVI-HPLC is expected to be a promising candidate for bioanalysis in therapeutic drug monitoring or pharmacokinetic and toxicology studies in the future.
    Keywords:  Column-switching; Large volume injection; Ultrasound-assisted micellar cleanup; Zebrafish
    DOI:  https://doi.org/10.1016/j.ultsonch.2022.105998
  5. J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Mar 30. pii: S1570-0232(22)00132-5. [Epub ahead of print]1198 123228
    Cyclophosphamide, hydroxycyclophosphamide and carboxyethyl phosphoramide mustard quantification with liquid chromatography mass spectrometry in a single run human plasma samples: A rapid and sensitive method development.
    Kripa Shanker Kasudhan, Ajay Patial, Nancy Mehra, Savita Verma Attri, Pankaj Malhotra, Smita Pattanaik, Deepesh Lad, Amol N Patil.
      A novel method for simultaneous quantification of cyclophosphamide along with its two major metabolites namely 4-hydroxycyclophosphamide (HCy) and carboxyethyl phosphoramide mustard (CEPM) in a single sample run was demonstrated in the present study. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) instrument was used for analysis. Semicarbazide was used as a stabilizing agent for HCy whereas ifosfamide, hexamethyl phosphoramide mustard and deuterated CEPM were the internal standards for quantification of Cy, HCy and CEPM respectively. Chromatographic separation was achieved by Chromsystems C18 reverse-phase column (50 mm × 4.6 mm, particle size 3.2 µm). The mobile phase was composed of eluent A (2 mM ammonium acetate in water with 2% formic acid) and eluent B (100 % acetonitrile). The flow rate was 1 ml/min. Linearity of the assay was assured in the range of 19.53 ng/ml to 10,000 ng/ml concentration in human plasma, which is adequate for pharmacokinetic studies of any dose Cy used clinically. The quality control(QC) accuracy was between 99.58% and 101.62%, 97.85% to 103.53% and 99.64% to 100.10% for Cy, HCy and CEPM respectively. Precision limits for QC samples were between 3.9% and 9.4%, 5.2% to 8.9% and 1.8% to 9.2% respectively. The analytical method was validated in ten leukaemia patients undergoing haploidentical hematopoietic cell transplantation.
    Keywords:  Carboxyethyl phosphoramide mustard; Cyclophosphamide; Hydroxy cyclophosphamide; Liquid chromatography mass spectrometry; Post transplant
    DOI:  https://doi.org/10.1016/j.jchromb.2022.123228
  6. Talanta. 2022 Jun 01. pii: S0039-9140(22)00135-7. [Epub ahead of print]243 123339
    Separation of isomers using a differential mobility analyser (DMA): Comparison of experimental vs modelled ion mobility.
    A Bianco, I Neefjes, D Alfaouri, H Vehkamäki, T Kurtén, L Ahonen, M Passananti, J Kangasluoma.
      Mass spectrometry is uniquely suited to identify and quantify environmentally relevant molecules and molecular clusters. Mass spectrometry alone is, however, not able to distinguish between isomers. In this study, we demonstrate the use of both an experimental set-up using a differential mobility analyser, and computational ion mobility calculations for identification of isomers. In the experimental set-up, we combined electrospray ionisation with a differential mobility analyser time-of-flight mass spectrometer to separate environmentally relevant constitutional isomers, such as catechol, resorcinol and hydroquinone, and configurational isomers, such as cyclohexanediols and fatty acids (i.e., oleic and elaidic acids). Computational ion mobility predictions were obtained using the Ion Mobility Software (IMoS) program. We find that isomer separation can be achieved with the differential mobility analyser, while for catechol, resorcinol and hydroquinone, the computational predictions can reproduce the experimental order of the ion mobilities between the isomers, confirming the isomer identification. Our experimental set-up allows analysis both in the gas and liquid phase. The differential mobility analyser can, moreover, be combined with any mass spectrometry set-up, making it a versatile tool for the separation of isomers.
    Keywords:  Differential mobility analyser; Electrospray ionisation; Ion mobility; Isobaric ions; Mass spectrometry
    DOI:  https://doi.org/10.1016/j.talanta.2022.123339
  7. J Biomed Res. 2022 Feb 28. 109-119
    Simultaneous determination of clopidogrel, 2-oxo-clopidogrel, and the thiol metabolite of clopidogrel in human plasma by LC-MS/MS.
    Lei Xu, Ran Li, Juan Li, Zhou Dong, Jiaxin Zong, Chuchu Tan, Zekang Ye, Lu Shi, Xiaoxuan Gong, Chunjian Li.
      Clopidogrel is a pro-drug which needs two-step metabolism to produce the active thiol metabolite. This study aimed to explore an efficient method to simultaneously determine the plasma clopidogrel, 2-oxo-clopidogrel (2-Oxo-CLP), and the clopidogrel active metabolite (CAM). A high-throughput liquid chromatography tandem mass spectrometry (LC-MS/MS) was therefore developed. The analytes were extracted from plasma by using methyl tert-butyl ether (MTBE). Chromatographic separation was performed on a C18 column under an isocratic elution, accompanied with acetonitrile and deionized water containing 0.1% formic acid. After optimizing the condition of LC-MS/MS, a stable linearity was observed in the standard curves over the concentration ranges of 0.05 to 50.0 ng/mL for clopidogrel, 0.5 to 50.0 ng/mL for 2-Oxo-CLP, and 0.5 to 100 ng/mL for clopidogrel active metabolite derivative (CAMD). The retention time was 4.78 minutes, 3.79 minutes, 3.59 minutes, and 4.82 minutes for clopidogrel, 2-Oxo-CLP, CAMD, and internal standard, respectively. Both the relative standard deviation and the relative error were within the requirement of operating criteria. No significant degradation of clopidogrel, 2-Oxo-CLP, and CAMD occurred under different storage conditions. This method was successfully validated in 3 patients with coronary artery disease. The results showed that the current LC-MS/MS method was efficient for simultaneously detecting clopidogrel, 2-Oxo-CLP, and CAM with fine linearity, accuracy, precision, and stability.
    Keywords:  clopidogrel; coronary artery disease; drug metabolites; liquid chromatography tandem mass spectrometry
    DOI:  https://doi.org/10.7555/JBR.36.20210125
  8. Int J Anal Chem. 2022 ;2022 5486290
    Simultaneous Determination of Fifteen Polyphenols in Fruit Juice Using Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry Combining Dispersive Liquid-Liquid Microextraction.
    Yuxiu Li, Zengyang He, Youmei Bao, Qingsheng Zhu, Yong Ning, Zhenfeng Tian, Xiaolan Zhu.
      Polyphenols are secondary metabolites of plants and used as effective antioxidants in dietary supplements, whose main sources are fruits, vegetables, and grains. To clarify the content and distribution of polyphenols in different fruit species samples accurately, a rapid and sensitive ultrahigh-pressure liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method combining dispersive liquid-liquid microextraction (DLLME) was developed for quantitative determination of fifteen polyphenol compounds in fruit juice. In this method, the targets were first extracted from 1 g of fruit juice sample using 10 mL of 80% ethanol solution by ultrasonic-assisted extraction (UAE). Then, 1.0 mL of UAE extracted solution, 60 μL of n-octanol and 2.0 mL of H2O were performed in the following DLLME procedure. A C18 reversed-phase column, ZORBAX SB (100 × 4.6 mm, 3.5 μm), was proposed under gradient elution with 0.1% formic acid aqueous solution and methanol mobile phases for the determination of 15 polyphenols, allowing us to obtain polyphenolic profiles in less than 23.0 min. Under the optimum conditions, the enrichment factors ranged from 162 to 194. The results showed that the 15 polyphenols had linear correlation coefficients (R 2) more than 0.99. The limits of detection (LODs) were between 18.3 and 103.5 ng/g, and the average recoveries were between 96.9 and 116.3% with interday relative standard deviations (RSDs) ranging from 4.4 to 8.2% in all cases. The method was successfully applied to the analysis of real fruit juice samples and presented itself as a simple, rapid, practical, and environment-friendly technique.
    DOI:  https://doi.org/10.1155/2022/5486290
  9. Biol Pharm Bull. 2022 ;45(4): 421-428
    Development of a Method of Liquid Chromatography Coupled with Tandem Mass Spectrometry for Simultaneous Determination of Linezolid and Tedizolid in Human Plasma.
    Yuki Sato, Yoh Takekuma, Takayuki Daisho, Hitoshi Kashiwagi, Shungo Imai, Mitsuru Sugawara.
      It is important to select appropriate antibiotics for infection control. Linezolid and tedizolid are newly developed and synthesized oxazolidinone antibacterial agents. It has been pointed out that there is a relationship between a high plasma concentration of the target drug and incidence of adverse effects, although it has been reported that neither linezolid nor tedizolid requires dose adjustment according to renal function. Due to the high incidence of adverse effects, both are often switched. Precise plasma concentration control by therapeutic drug monitoring (TDM) is desirable for reducing the adverse effects of both drugs and obtaining a better therapeutic effect. In this study, we aimed to establish a method for simultaneous quantification of linezolid and tedizolid in human plasma using LC coupled with tandem mass spectrometry. Sample preparation was performed by a simple operation with acetonitrile. Linezolid and tedizolid were separated by an octadecylsilyl column using a gradient elution of acetonitrile in aqueous 0.1% formic acid solution and were detected in the positive ion electrospray mode with multiple reaction monitoring. Quantification of linezolid and tedizolid ranged from 0.5 to 50 and 0.5 to 20 µg/mL, respectively. The intra-day and inter-day precision and accuracy of data were assessed and found to be acceptable. The developed method was successfully applied to measurement of the concentrations of linezolid and tedizolid. This simple method, which can simultaneously quantify both drug concentrations for daily TDM, could contribute to safer treatment of patients.
    Keywords:  LC/MS; linezolid; plasma concentration; simultaneous quantification; tedizolid; therapeutic drug monitoring
    DOI:  https://doi.org/10.1248/bpb.b21-00798
  10. J Am Soc Mass Spectrom. 2022 Apr 04.
    In Silico Collision Cross Section Calculations to Aid Metabolite Annotation.
    Susanta Das, Kiyoto Aramis Tanemura, Laleh Dinpazhoh, Mithony Keng, Christina Schumm, Lydia Leahy, Carter K Asef, Markace Rainey, Arthur S Edison, Facundo M Fernández, Kenneth M Merz.
      The interpretation of ion mobility coupled to mass spectrometry (IM-MS) data to predict unknown structures is challenging and depends on accurate theoretical estimates of the molecular ion collision cross section (CCS) against a buffer gas in a low or atmospheric pressure drift chamber. The sensitivity and reliability of computational prediction of CCS values depend on accurately modeling the molecular state over accessible conformations. In this work, we developed an efficient CCS computational workflow using a machine learning model in conjunction with standard DFT methods and CCS calculations. Furthermore, we have performed Traveling Wave IM-MS (TWIMS) experiments to validate the extant experimental values and assess uncertainties in experimentally measured CCS values. The developed workflow yielded accurate structural predictions and provides unique insights into the likely preferred conformation analyzed using IM-MS experiments. The complete workflow makes the computation of CCS values tractable for a large number of conformationally flexible metabolites with complex molecular structures.
    DOI:  https://doi.org/10.1021/jasms.1c00315
  11. BMC Genomics. 2022 Apr 06. 23(Suppl 1): 269
    Explore potential disease related metabolites based on latent factor model.
    Yongtian Wang, Liran Juan, Jiajie Peng, Tao Wang, Tianyi Zang, Yadong Wang.
       BACKGROUND: In biological systems, metabolomics can not only contribute to the discovery of metabolic signatures for disease diagnosis, but is very helpful to illustrate the underlying molecular disease-causing mechanism. Therefore, identification of disease-related metabolites is of great significance for comprehensively understanding the pathogenesis of diseases and improving clinical medicine.
    RESULTS: In the paper, we propose a disease and literature driven metabolism prediction model (DLMPM) to identify the potential associations between metabolites and diseases based on latent factor model. We build the disease glossary with disease terms from different databases and an association matrix based on the mapping between diseases and metabolites. The similarity of diseases and metabolites is used to complete the association matrix. Finally, we predict potential associations between metabolites and diseases based on the matrix decomposition method. In total, 1,406 direct associations between diseases and metabolites are found. There are 119,206 unknown associations between diseases and metabolites predicted with a coverage rate of 80.88%. Subsequently, we extract training sets and testing sets based on data increment from the database of disease-related metabolites and assess the performance of DLMPM on 19 diseases. As a result, DLMPM is proven to be successful in predicting potential metabolic signatures for human diseases with an average AUC value of 82.33%.
    CONCLUSION: In this paper, a computational model is proposed for exploring metabolite-disease pairs and has good performance in predicting potential metabolites related to diseases through adequate validation. The results show that DLMPM has a better performance in prioritizing candidate diseases-related metabolites compared with the previous methods and would be helpful for researchers to reveal more information about human diseases.
    Keywords:  Disease diagnosis; Disease similarity; Matrix decomposition; Metabolite
    DOI:  https://doi.org/10.1186/s12864-022-08504-w
  12. Proteomics Clin Appl. 2022 Apr 08. e2200017
    Are Mass Spectrometry Imaging-Based Diagnostics Becoming Reality?
    Erin H Seeley.
       : Traditional histological tissue-based diagnostics have been slow and often require large numbers of sections to interrogate for several different proteins with immunohistochemical stains. Often, due to small biopsy size, there is not sufficient material available to carry out all the desired tests on a patient sample. Mass Spectrometry Imaging (MSI) enables the simultaneous detection of hundreds to thousands of analytes from a single tissue section. In recent years, great strides have been made to standardize MSI workflows and data analysis to make it an accessible tool for clinicians to use in patient diagnoses. This commentary highlights the advances by Janßen, et al. toward this goal. This article is protected by copyright. All rights reserved.
    Keywords:  machine learning; mass spectrometry imaging; tissue diagnostics
    DOI:  https://doi.org/10.1002/prca.202200017
  13. Methods Enzymol. 2022 ;pii: S0076-6879(21)00509-7. [Epub ahead of print]665 49-71
    Adding a diazo-transfer reagent to culture to generate secondary metabolite probes for click chemistry.
    Michael P Gotsbacher, Rachel Codd.
      Converting discrete microbial metabolites into chemical probes for chemical biology and medicinal chemistry studies is typically preceded by lengthy purification and chemical derivatization processes. Standard practice involves purifying the target microbial metabolite from culture, followed by derivatization and/or conjugation chemistry to convert the pure metabolite into a tagged species. This multistep approach can pose difficulties in generating useful yields of chemical probes, particularly in the case of low-abundant metabolites, as common in metabolomes. This chapter describes a methodological approach to simplify the steps towards generating chemical probes from complex mixtures, that combines: (a) tailored purification processes; (b) compound identification using state-of-the-art tandem mass spectrometry and data-dependent fragmentation; and (c) in situ bioorthogonal bioconjugation chemistries. The combination of these methods, as illustrated by the conversion of a set of amine-bearing metabolites to the cognate azide analogs suitable for biotinylation through azide-alkyne cycloaddition, describes a powerful approach to access new chemical probes of low-abundant metabolites that might otherwise be inaccessible using traditional methods.
    Keywords:  Amine-to-azido conversion of natural products; Azido-desferrioxamine siderophores for click chemistry; Diazo-transfer reagent; Hydroxamic acid siderophores
    DOI:  https://doi.org/10.1016/bs.mie.2021.12.003
  14. Front Pharmacol. 2022 ;13 805782
    Fluxomics - New Metabolomics Approaches to Monitor Metabolic Pathways.
    Abdul-Hamid Emwas, Kacper Szczepski, Inas Al-Younis, Joanna Izabela Lachowicz, Mariusz Jaremko.
      Fluxomics is an innovative -omics research field that measures the rates of all intracellular fluxes in the central metabolism of biological systems. Fluxomics gathers data from multiple different -omics fields, portraying the whole picture of molecular interactions. Recently, fluxomics has become one of the most relevant approaches to investigate metabolic phenotypes. Metabolic flux using 13C-labeled molecules is increasingly used to monitor metabolic pathways, to probe the corresponding gene-RNA and protein-metabolite interaction networks in actual time. Thus, fluxomics reveals the functioning of multi-molecular metabolic pathways and is increasingly applied in biotechnology and pharmacology. Here, we describe the main fluxomics approaches and experimental platforms. Moreover, we summarize recent fluxomic results in different biological systems.
    Keywords:  flux; fluxomics; mass spectrometry (MS); metabolomics; nuclear magnetic resonance (NMR); pharmacometabolomics
    DOI:  https://doi.org/10.3389/fphar.2022.805782
  15. Anal Chem. 2022 Apr 07.
    Open Search of Peptide Glycation Products from Tandem Mass Spectra.
    Michelle T Berger, Daniel Hemmler, Philippe Diederich, Michael Rychlik, James W Marshall, Philippe Schmitt-Kopplin.
      Identification of chemically modified peptides in mass spectrometry (MS)-based glycation studies is a crucial yet challenging task. There is a need to establish a mode for matching tandem mass spectrometry (MS/MS) data, allowing for both known and unknown peptide glycation modifications. We present an open search approach that uses classic and modified peptide fragment ions. The latter are shifted by the mass delta of the modification. Both provide key structural information that can be used to assess the peptide core structure of the glycation product. We also leverage redundant neutral losses from the modification side chain, introducing a third ion class for matching referred to as characteristic fragment ions. We demonstrate that peptide glycation product MS/MS spectra contain multidimensional information and that most often, more than half of the spectral information is ignored if no attempt is made to use a multi-step matching algorithm. Compared to regular and/or modified peptide ion matching, our triple-ion strategy significantly increased the median interpretable fraction of the glycation product MS/MS spectra. For reference, we apply our approach for Amadori product characterization and identify all established diagnostic ions automatically. We further show how this method effectively applies the open search concept and allows for optimized elucidation of unknown structures by presenting two hitherto undescribed peptide glycation modifications with a delta mass of 102.0311 and 268.1768 Da. We characterize their fragmentation signature by integration with isotopically labeled glycation products, which provides high validity for non-targeted structure identification.
    DOI:  https://doi.org/10.1021/acs.analchem.2c00388
  16. J Chromatogr A. 2022 Mar 22. pii: S0021-9673(22)00188-1. [Epub ahead of print]1671 462990
    Simultaneous solvent extraction and quantification of eleven amine compounds related to Chemical Weapon Convention in soils via hydrophilic interaction liquid chromatography-tandem mass spectrometry.
    Pei-Yu Jiang, Ling Yuan, Shi-Lei Liu, Qiao Lv, Hui-Lan Yu, Long-Hui Liang, Yang Yang, Chang-Cai Liu.
      The detection of Chemical Weapon Convention (CWC)-related amine compounds including the precursors or degradation products of V-type organophosphorus nerve agent, nitrogen mustard and 3-quinuclidinyl benzilate is an important aspect for verifying their intact chemical warfare agents. This work focuses on the development of a novel formulation for the simultaneous solvent extraction of eleven CWC-related amine compounds, from the four-type soil matrices including environmental standard soil, sand, clay, and loam. Extracts were well separated on the hydrophilic interaction liquid chromatography (HILIC) and then detected by MS/MS multiple reaction monitoring mode. The type and component of solvent mixtures were optimized to cover a wide range of polarity over all eleven amine compounds with high extraction efficiencies. Extraction parameters, such as the proportion of methanol, water and NH4OH, the times and the period of extraction, and volumes of extraction solution were optimized. The results indicated that a mixed solvent of methanol/water (44:53, v/v) in 3.0% NH4OH was the optimal formulation for extraction of all 11 analytes with high mean extraction recoveries (64.4-96.1%). Specificity and sensitivity were well improved by the good separation of 11 analytes from four-type soil matrices using these optimized HILIC parameters. This method was fully validated for each analyte in four soil matrices. The linear range of 11 analytes was 0.50/0.75-500 ng·g-1 with correlation coefficient (R2) ≥0.990, and intra/inter-day accuracies were 70.3-125% with relative standard deviation (RSD) ≤19.3%. Limit of detection (LOD) of 11 analytes ranged from 0.01 to 0.5 ng·g-1, which was far lower than those reported in previous studies. The built method accomplishes simultaneously quantitative and trace measurement of all eleven CWC-related amine compounds within a single solvent extraction and detection. It only takes a small amount of soil samples and possesses the highest sensitivity over all previous methods. This study provides an optional recommended operating procedure for determination of CWC-related amine compounds in four typical types of complex soils during chemical weapons verification.
    Keywords:  Amine compounds; Chemical weapons verification; Environmental soils; HILIC-MS/MS analysis; Solvent extraction
    DOI:  https://doi.org/10.1016/j.chroma.2022.462990
  17. Food Chem. 2022 Mar 30. pii: S0308-8146(22)00819-6. [Epub ahead of print]387 132857
    Novel carrier-mediated membrane-assisted three-phase liquid-liquid extraction coupled with liquid chromatography-mass spectrometry for the determination of eight biogenic amines in foods.
    Tian-Tian Zhou, Aziguli Yigaimu, Turghun Muhammad, Peng-Li Jian, Li-Na Sha, Shu-Biao Zhang.
      Analysis of biogenic amines (BAs) is of great importance due to their toxicity and usage as indicators of food freshness. In this study, membrane-assisted three-phase liquid-liquid extraction (MA-3pLLE) was proposed to integrate extraction and back-extraction into a single step using a specially designed U-shaped device. Parameters affecting the performance of the extraction method were optimized. Coupled with liquid chromatography-mass spectrometry, the method was successfully applied for the simultaneous determination of eight BAs without derivatization in apple juice, orange juice, red wine, soy sauce and milk granules, with satisfactory recoveries and RSDs. The calibration curve of the method was linear in the range of 1.00~100.00 ng/mL, with a correlation coefficient (r2) ≥ 0.9908. The limits of detection were in the range of 0.03~1.00 ng/mL. MA-3pLLE is efficient, reproducible, and green and has great potential for application in the one-step extraction of analytes from complex matrices.
    Keywords:  Biogenic amines; Carrier agent; Liquid chromatography–mass spectrometry; Membrane separation; Three-phase liquid–liquid extraction
    DOI:  https://doi.org/10.1016/j.foodchem.2022.132857
  18. J Pharm Biomed Anal. 2022 Mar 26. pii: S0731-7085(22)00159-5. [Epub ahead of print]214 114738
    Determination of selected α-keto acids in dried blood samples using HPLC with fluorescence detection.
    Roman Kanďár, Michal Kopčil, Lenka Laštovičková.
      The determination of α-keto acids derived from amino acids is currently the most reliable approach for the diagnosis of some congenital metabolic diseases. An HPLC method for the simultaneous measurement of selected α-keto acids in dried blood samples has been developed and evaluated. Blood spot samples from a group of healthy blood donors were collected onto #903 Specimen Collection Paper. Prior the separation, the α-keto acids were derivatized with 1,2-diamino-4,5-dimethoxybenzene to the corresponding 3-substituted-6,7-dimethoxy-2(1 H)-quinoxalinol derivatives. For the separation, a reverse-phase column LichroCart 125-4, Purospher RP-18e, 5 µm, was used. The mixture of 25% ACN in deionized water (mobile phase A) and 100% ACN (mobile phase B) were used for a gradient elution of α-keto acids derivatives. Analytical performance of this method is satisfactory for all α-keto acids. The intra-assay and inter-assay coefficients were below 10% and recoveries were close to 100%. We have developed relatively simple, rapid, selective and sufficiently sensitive HPLC method with fluorescence detection for the determination of selected α-keto acids in dried blood samples. The presented method is suitable for clinical testing purposes.
    Keywords:  1,2-Diamino-4,5-dimethoxybenzene; Dried blood spot; HPLC with fluorescence detection; α-Keto acids
    DOI:  https://doi.org/10.1016/j.jpba.2022.114738
  19. Ther Drug Monit. 2022 Apr 04.
    High-Sensitivity and High-Throughput Quantification of Everolimus in Human Whole Blood using Ultra-High-Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry.
    Chika Miyagi, Ryota Tanaka, Kenshiro Hirata, Takuma Watanabe, Ryosuke Tatsuta, Shigeyuki Miyamura, Hiroki Itoh.
       BACKGROUND: Rigorous dose adjustment by therapeutic drug monitoring (TDM) is recommended when everolimus (EVR) is administered for immunosuppression. In this study, the authors developed a highly sensitive ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for measuring EVR concentrations in whole blood using a high-throughput solid-phase extraction method for sample pretreatment. Furthermore, the blood EVR concentrations in routine TDM samples from patients who underwent renal transplantation measured using the established UHPLC-MS/MS method were compared with those measured using the latex agglutination turbidimetric immunoassay (LTIA).
    METHODS: Blood samples were pretreated by solid-phase extraction using a 96-well HLB µElution plate. The clinical application of the newly developed method was evaluated using 87 blood samples from 19 kidney transplant patients.
    RESULTS: The calibration curve showed good linearity over a wide range of 0.1-50 ng/mL, with relative error ≤15% obtained from back-calculation of calibrators, and ≤20% for the lower limit of quantification. Within-batch and batch-to-batch accuracies and precisions fulfilled the acceptance criteria of the US Food and Drug Administration guidelines for bioanalytical method validation. The extraction recovery rates were good (≥65.2%), and almost no matrix effects were found in any of the quality control samples. Blood EVR concentrations measured by UHPLC-MS/MS were positively correlated with those measured by LTIA. A Bland-Altman plot indicated that the UHPLC-MS/MS method yielded better measurements than the LTIA method, regardless of the concentration.
    CONCLUSIONS: Therefore, the authors succeeded in developing a novel high-sensitivity and high-throughput method for measuring blood EVR concentration by UHPLC-MS/MS using a µElution plate for sample pretreatment.
    DOI:  https://doi.org/10.1097/FTD.0000000000000985
  20. Front Physiol. 2022 ;13 826740
    Bile Acid Detection Techniques and Bile Acid-Related Diseases.
    Xiang Zhao, Zitian Liu, Fuyun Sun, Lunjin Yao, Guangwei Yang, Kexin Wang.
      Bile acid is a derivative of cholinergic acid (steroidal parent nucleus) that plays an important role in digestion, absorption, and metabolism. In recent years, bile acids have been identified as signaling molecules that regulate self-metabolism, lipid metabolism, energy balance, and glucose metabolism. The detection of fine changes in bile acids caused by metabolism, disease, or individual differences has become a research hotspot. At present, there are many related techniques, such as enzyme analysis, immunoassays, and chromatography, that are used for bile acid detection. These methods have been applied in clinical practice and laboratory research to varying degrees. However, mainstream detection technology is constantly updated and replaced with the passage of time, proffering new detection technologies. Previously, gas chromatography (GS) and gas chromatography-mass spectrometry (GC-MS) were the most commonly used for bile acid detection. In recent years, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has developed rapidly and has gradually become the mainstream bile acid sample separation and detection technology. In this review, the basic principles, development and progress of technology, applicability, advantages, and disadvantages of various detection techniques are discussed and the changes in bile acids caused by related diseases are summarized.
    Keywords:  bile acid; chromatography; detection techniques; enzyme analysis; related diseases
    DOI:  https://doi.org/10.3389/fphys.2022.826740
  21. Anal Chem. 2022 Apr 07.
    Parallel Operation of Electron Ionization and Chemical Ionization for GC-MS Using a Single TOF Mass Analyzer.
    Steffen Bräkling, Kai Kroll, Carsten Stoermer, Urs Rohner, Marc Gonin, Thorsten Benter, Hendrik Kersten, Sonja Klee.
      This work describes a novel mass spectrometer coupled to gas chromatography (GC-MS) that simultaneously displays the mass spectral information of electron (EI)- and chemical ionization (CI)-generated ion populations for a single chromatographic peak. After GC separation, the eluent is equally split and supplied in parallel to an EI and a novel CI source, both operating continuously. Precise switching of the ion optics provides the exact timing to consecutively extract the respective ion population from both sources and transfer them into a time-of-flight (TOF) mass analyzer. This technique enables the acquisition of complementary information from both ion populations (EI and CI) within a single chromatographic run and with sufficient data points to retain the chromatographic fidelity. The carefully designed GC transfer setup, fast ion optical switching, and synchronized TOF data acquisition system provide an automatic and straightforward spectral alignment of two ion populations. With an eluent split ratio of about 50% between the two ion sources, instrument detection limits of <40 fg on the column (octafluoronaphthalene) for the EI and <2 pg (benzophenone) for the CI source were obtained. The system performance and the additional analytical value for compound identification are demonstrated by means of different common GC standard mixtures and a commercial perfume sample of unknown composition.
    DOI:  https://doi.org/10.1021/acs.analchem.2c00933
  22. Drug Test Anal. 2022 Apr 09.
    A quantitative method for the simultaneous detection of SR9009 and SR9011 in equine plasma using liquid chromatography-electrospray ionization-tandem mass spectrometry.
    Young Beom Kwak, Jundong Yu, Hye Hyun Yoo.
      SR9009 and SR9011 are metabolic modulators pharmacologically targeting REV-ERB receptors as synthetic agonists. A liquid chromatography-tandem mass spectrometry method for the detection of SR9009 and SR9011 in equine plasma was developed and validated. Plasma samples were pretreated by protein precipitation with methanol and were loaded onto an ACQUITY ultra performance liquid chromatography high-strength silica C18 column (2.1 × 150 mm, 1.8 μm) for chromatographic separation. The mobile phase consisted of 5 mM ammonium formate (pH 3.0) in distilled water and 0.1% formic acid in acetonitrile, and a gradient elution was used at a flow rate of 0.25 mL/min. For the mass spectrometry detection, the selected reaction monitoring mode was used with transitions of 438.2→124.9 for SR9009, 479.2→125.1 for SR9011, and 292.2→109.1 for the internal standard (testosterone-d3) in the positive ionization mode. The linearity, lower limit of quantification, intra- and inter-day precision, accuracy, matrix effect, recovery, and stability were evaluated. The method was found to be accurate and reproducible for the quantitation of SR9009 and SR9011. The developed method was successfully applied to plasma samples of thoroughbreds injected intramuscularly with SR9009.
    Keywords:  LC-MS/MS; REV-ERB agonist; SR9009; SR9011; equine
    DOI:  https://doi.org/10.1002/dta.3271
  23. Drug Test Anal. 2022 Apr 06.
    A single LC-MS/MS validated method for tulathromycin quantification in plasma, seminal plasma and urine to be applied in a pharmacokinetic study in bull.
    Andrea Barbarossa, Anisa Bardhi, Teresa Gazzotti, Gaetano Mari, Giampiero Pagliuca.
      Tulathromycin is a macrolide antibiotic generally used for the treatment of respiratory diseases in cattle and swine. This work proposes an improvement of a previously published LC-MS/MS method for tulathromycin determination in pig serum, here validated in three different bull matrices: plasma, seminal plasma and urine. The approach is based on a quick protein precipitation with acetonitrile, filtration and sample dilution before injection, allowing to rapidly process large batches of samples. Analytes separation was obtained using a BEH C18 (50 × 2.1 mm, 1.7 μm) column, maintained at 40 °C with a chromatographic run of 5 min. The method was fully validated over concentration ranges suitable for field levels of tulathromycin found in each matrix (0.01-1 μg/mL for plasma, 0.05-5 μg/mL for seminal plasma and 0.1-10 μg/mL for urine), showing good linearity during each day of testing (R2 always >0.99). Accuracy and precision were within ±15% at all QC concentrations in all the three matrices. Furthermore, the use of tulathromycine-d7 as internal standard mitigated the potential impacts of matrix effect. The validated technique was successfully applied to samples collected during a pharmacokinetic study in bulls, allowing to monitor tulathromycin concentrations over time in the three matrices. To our knowledge, this is the first validated approach for LC-MS/MS quantification of tulathromycin in seminal plasma and urine.
    Keywords:  LC-MS; Pharmacokinetics; Plasma; Seminal plasma; Tulathromycin; Urine
    DOI:  https://doi.org/10.1002/dta.3270
  24. Histochem Cell Biol. 2022 Apr 07.
    A simple preparation step to remove excess liquid lipids in white adipose tissue enabling improved detection of metabolites via MALDI-FTICR imaging MS.
    Qian Wang, Na Sun, Thomas Kunzke, Achim Buck, Jian Shen, Verena M Prade, Barbara Stöckl, Jun Wang, Annette Feuchtinger, Axel Walch.
      Matrix-assisted laser desorption ionization (MALDI) Fourier transform ion cyclotron resonance (FTICR) imaging mass spectrometry (MS) is a powerful technology used to analyze metabolites in various tissues. However, it faces significant challenges in studying adipose tissues. Poor matrix distribution and crystallization caused by excess liquid lipids on the surface of tissue sections hamper m/z species detection, an adverse effect that particularly presents in lipid-rich white adipose tissue (WAT). In this study, we integrated a simple and low-cost preparation step into the existing MALDI-FTICR imaging MS pipeline. The new method-referred to as filter paper application-is characterized by an easy sample handling and high reproducibility. The aforementioned filter paper is placed onto the tissue prior to matrix application in order to remove the layer of excess liquid lipids. Consequently, MALDI-FTICR imaging MS detection was significantly improved, resulting in a higher number of detected m/z species and higher ion intensities. After analyzing various durations of filter paper application, 30 s was found to be optimal, resulting in the detection of more than 3700 m/z species. Apart from the most common lipids found in WAT, other molecules involved in various metabolic pathways were detected, including nucleotides, carbohydrates, and amino acids. Our study is the first to propose a solution to a specific limitation of MALDI-FTICR imaging MS in investigating lipid-rich WAT. The filter paper approach can be performed quickly and is particularly effective for achieving uniform matrix distribution on fresh frozen WAT while maintaining tissue integrity. It thus helps to gain insight into the metabolism in WAT.
    Keywords:  Filter paper; Layer of excess liquid lipids; MALDI-FTICR imaging MS; Metabolite; White adipose tissue
    DOI:  https://doi.org/10.1007/s00418-022-02088-y
  25. Metabolomics. 2022 Apr 06. 18(4): 22
    NEWS: The 2022 Metabolomics publication awards.
    Royston Goodacre.
      
    DOI:  https://doi.org/10.1007/s11306-022-01882-y
  26. Nat Rev Endocrinol. 2022 Apr 07.
    The emerging role of lipidomics in prediction of diseases.
    Xianlin Han.
      
    DOI:  https://doi.org/10.1038/s41574-022-00672-9
  27. Mikrochim Acta. 2022 Apr 04. 189(5): 175
    Carbon quantum dots-functionalized silica stationary phase for pharmaceutical analysis by a green liquid chromatography mode.
    Qi Wu, Jiying Song, Yanli Wang, Hui Li, Liang Zhao, Haitao Lv, Xian-En Zhao.
      Facing the trends of green chemistry, this work tries to find a novel material for per aqueous liquid chromatography (PALC) aiming to reduce the consumption of hazardous reagents. As a kind of green nanomaterials, the chromatographic performance of carbon quantum dots (CQDs) in PALC was rarely studied. Here, hydrophilic CQDs were prepared by a simple hydrothermal method using citric acid and ethylenediamine as carbon sources. The synthesized CQDs with functional groups of amino, carboxyl, and hydroxyl were decorated on silica gels forming a novel Si-CQDs stationary phase. This Si-CQDs column possesses the typical retention feature of PALC. Compounds with different polarities including hydrophobic pesticides, polar sulfonamides, β-adrenoceptor blockers and agonists, as well as hydrophilic nucleosides and bases obtained satisfactory separation on this Si-CQDs column under PALC mode, even better resolution than in hydrophilic interaction liquid chromatography (HILIC) mode. A mixture of four sulfonamides can be separated within 6 min using a mobile phase containing only 5% acetonitrile, and the resolution achieves 2.39, 2.13, and 1.83 with an average column efficiency of 1400. For certain compounds, this Si-CQDs column showed better separation performance than commercial SiO2 column, NH2 column, and C18 column. The retention mechanism includes hydrophobic and electrostatic interactions due to the multifunctional groups of CQDs. This Si-CQDs column achieved the rapid detection of residual sulfonamides in milk with simplified sample pretreatment process and the detection of atenolol in commercial atenolol tablets. The developed Si-CQDs column has great prospects in low-cost and environmentally friendly separation and analysis.
    Keywords:  Carbon quantum dots; Green liquid chromatography; Per aqueous liquid chromatography
    DOI:  https://doi.org/10.1007/s00604-022-05291-9
  28. Biomed Chromatogr. 2022 Apr 02. e5378
    Characterisation and traceability of two generations of standard reference material for the measurement of vitamin K1 (phylloquinone) at endogenous concentrations in human plasma and serum.
    D J Card, E C Freke, D J Harrington.
      Vitamin K is an essential micronutrient required for blood coagulation, regulation of vascular calcification and bone mineralisation. Plasma and serum measurements of vitamin K1 (phylloquinone, K1 ) made using high performance liquid chromatography with fluorescence detection, or liquid chromatography with tandem mass spectrometry are used clinically and in population studies to assess vitamin K status. Standard reference materials provide a validation tool for laboratories, helping assure clinical diagnosis and the comparability of data from different populations. We manufactured two K1 standard reference materials, in 2009 (KEQAS SRM-001) and in 2019 (KEQAS SRM-002). The target concentrations of K1 were assigned to each SRM using the All Laboratory Trimmed Mean of results reported by selected laboratories enrolled in the Vitamin K External Quality Assurance Scheme (KEQAS). The assigned concentrations of K1 for KEQAS SRM-001 and SRM-002 were 0.25 and 0.36 μg/L respectively. In 2019 KEQAS SRM-001 was re-analysed simultaneously with KEQAS SRM-002 to provide traceability between the two standards, therefore aiding comparability of analysis performed using these materials. Both standards were stored as aliquots at -80o C in the dark, annual re-analyse of the materials indicated that K1 is stable for at least twelve years in these conditions.
    Keywords:  Vitamin K; high performance liquid chromatography; mass spectrometry; phylloquinone; standard reference material
    DOI:  https://doi.org/10.1002/bmc.5378
  29. Anal Methods. 2022 Apr 06.
    A validated method for the rapid quantification of melatonin in over-the-counter hypnotics by the atmospheric pressure solid analysis probe (ASAP).
    Daniel Moser, Shah Hussain, Matthias Rainer, Thomas Jakschitz, Günther K Bonn.
      Melatonin is a hormone that regulates the biological day and night cycle. It is mainly produced by the pineal gland during the night. People suffering from insomnia use it as a soporific drug. The aim of this study was to develop a method for the rapid quantification of melatonin in hypnotics. For that purpose, atmospheric pressure solid analysis probe-assisted mass spectrometry was applied, where no chromatographic separation is needed. Thereby, one single analysis takes less than 1 min. Reference measurements were performed with ultra-high-performance liquid chromatography coupled with a quadrupole-time-of-flight mass spectrometer. Both methods were validated and real sample extracts were tested. The coefficients of determination were above 0.97 for both methods. The limits of detection and quantification were below 1 mg kg-1. Both methods gave comparable results. Moreover, the content of melatonin differed from the specified value in many samples. The highest and lowest observed deviations were 78% and 1%, respectively.
    DOI:  https://doi.org/10.1039/d2ay00352j
  30. J Chromatogr A. 2022 Mar 23. pii: S0021-9673(22)00190-X. [Epub ahead of print]1671 462992
    Comparison of three stationary phases in the separation of polyphenyls by liquid chromatography.
    C L Brown, L M Dornan, M J Muldoon, R T Hembre, P J Stevenson, P Manesiotis.
      We present herein new analytical protocols for the separation and structural elucidation of polyphenyls. Three commercially available chromatographic stationary phases are compared in the separation of these non-polar, unfunctionalized, positional isomers. Baseline separation of nine terphenyl and quaterphenyl isomers is achieved in under ten minutes using a rapid gradient elution HPLC method. Complete separation of these, and a further five polyphenyls, is demonstrated. We finally present a linear correlation between solvent accessible surface area and the retention times of these closely related compounds.
    Keywords:  HPLC method development; Quaterphenyls; Solvent accessible surface area
    DOI:  https://doi.org/10.1016/j.chroma.2022.462992
  31. Anal Bioanal Chem. 2022 Apr 05.
    Beyond Δ9-tetrahydrocannabinol and cannabidiol: chemical differentiation of cannabis varieties applying targeted and untargeted analysis.
    Manuela Carla Monti, Priska Frei, Sophie Weber, Eva Scheurer, Katja Mercer-Chalmers-Bender.
      Cannabis sativa (C. sativa) is commonly chemically classified based on its Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content ratios. However, the plant contains nearly 150 additional cannabinoids, referred to as minor cannabinoids. Minor cannabinoids are gaining interest for improved plant and product characterization, e.g., for medical use, and bioanalytical questions in the medico-legal field. This study describes the development and validation of an analytical method for the elucidation of minor cannabinoid fingerprints, employing liquid chromatography coupled to high-resolution mass spectrometry. The method was used to characterize inflorescences from 18 different varieties of C. sativa, which were cultivated under the same standardized conditions. Complementing the targeted detection of 15 cannabinoids, untargeted metabolomics employing in silico assisted data analysis was used to detect additional plant ingredients with focus on cannabinoids. Principal component analysis (PCA) was used to evaluate differences between varieties. The overall purpose of this study was to examine the ability of targeted and non-targeted metabolomics using the mentioned techniques to distinguish cannabis varieties from each other by their minor cannabinoid fingerprint. Quantitative determination of targeted cannabinoids already gave valuable information on cannabinoid fingerprints as well as inter- and intra-variety variability of cannabinoid contents. The untargeted workflow led to the detection of 19 additional compounds. PCA of the targeted and untargeted datasets revealed further subgroups extending commonly applied phenotype classification systems of cannabis. This study presents an analytical method for the comprehensive characterization of C. sativa varieties.
    Keywords:  Cannabinomics; Chemotaxonomy; High-resolution mass spectrometry; Metabolomics; Minor cannabinoids; Principal component analysis
    DOI:  https://doi.org/10.1007/s00216-022-04026-2
  32. Food Chem. 2022 Mar 29. pii: S0308-8146(22)00818-4. [Epub ahead of print]386 132856
    Untargeted metabolomics and proteomics approach using liquid chromatography-Orbitrap high resolution mass spectrometry to detect pork adulteration in Pangasius hypopthalmus meat.
    Anjar Windarsih, Suratno, Hendy Dwi Warmiko, Anastasia Wheni Indrianingsih, Abdul Rohman, Yaya Ihya Ulumuddin.
      Pangasius hypopthalmus is well known as a good source of protein. However, Pangasius hypopthalmus meat (PHM) can be adulterated with pork for economic concern, thus, analytical methods for authentication are required. Untargeted metabolomics and proteomics using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and chemometrics of principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) was successfully used to differentiate authentic and adulterated PHM with the good of fitness (R > 0.95) and good of predictivity (Q > 0.5). Metabolites of PC(o-18:0/18:2(9Z,12Z)) was found to be a potential marker for pork whereas DMPC (dimyristoylphosphatidylcholine) was a potential marker for PHM. Meanwhile, pork peptide marker of myoglobin (HPGDFGADAQGAMSK) and β-hemoglobin (FFESFGDLSNADAVMGNPK) could be identified. Both metabolomics and proteomics using LC-HRMS could detect pork at the lowest concentration level (0.5% w/w). In conclusion, untargeted metabolomics and proteomics using LC-HRMS in combination with chemometrics could be used as powerful methods to detect pork adulteration in fish meat.
    Keywords:  Halal authentication; Pangasius hypopthalmus meat; Pork; Proteomics; Untargeted metabolomics
    DOI:  https://doi.org/10.1016/j.foodchem.2022.132856
  33. Ther Drug Monit. 2022 Apr 04.
    Development and Validation of a Dried Blood Spot Assay Using UHPLC-MS/MS to Identify and Quantify 12 Antihypertensive Drugs and 4 Active Metabolites: Clinical Needs and Analytical Limitations.
    Laura E J Peeters, Soma Bahmany, Tim Dekker, Aya Aliawi, B van Domburg, Jorie Versmissen, Birgit C P Koch.
       PURPOSE: As non-adherence to antihypertensive drugs (AHDs) can increase the risk of cardiovascular events, hospitalization, and higher costs, there is a need for a reliable, objective, and easy method to assess non-adherence in patients. The dried blood spot (DBS) sampling method used to measure drug concentrations meets these requirements. For detecting non-adherence, identification is more important than quantification. Due to their use in clinical practice, it is important to measure multiple AHDs with a single method. Therefore, we developed and validated a single DBS method for 17 commonly used AHDs and 4 active metabolites using ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
    METHODS: Analytical validation of the DBS assay was performed in accordance with the guidelines on bioanalytical method validation of the European Medicines Agency (EMA) and US Food and Drug Administration (FDA), as well as the International Association of Therapeutic Drug Monitoring and Clinical Toxicology guidelines.
    RESULTS: We validated 12 out of the 17 AHDs according to the EMA and FDA requirements for bioanalytical method validation. Eleven AHDs were validated for both identification and quantification of drug concentrations, while nifedipine was only validated for identification. However, 5 of the 17 AHDs were excluded due to suboptimal validation results. Lercanidipine was excluded due to non-linearity, and all four AHDs measured in the negative mode of UHPLC-MS/MS were not in accordance with one or more of the acceptance criteria and were therefore excluded.
    CONCLUSION: The described method accurately measured AHDs in DBS, and can be used to determine non-adherence in patients. However, method validation revealed a challenging balance between analytical limitations and clinical needs when analyzing multiple drugs using the same method.
    DOI:  https://doi.org/10.1097/FTD.0000000000000984
  34. Methods Enzymol. 2022 ;pii: S0076-6879(21)00492-4. [Epub ahead of print]665 281-304
    Utilizing imaging mass spectrometry to analyze microbial biofilm chemical responses to exogenous compounds.
    Catherine S McCaughey, Michael A Trebino, Fitnat H Yildiz, Laura M Sanchez.
      Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is an appealing label-free method for imaging biological samples which focuses on the spatial distribution of chemical signals. This approach has been used to study the chemical ecology of microbes and can be applied to study the chemical responses of microbes to treatment with exogenous compounds. Specific conjugated cholic acids such as taurocholic acid (TCA), have been shown to inhibit biofilm formation in the enteric pathogen Vibrio cholerae and MALDI-IMS can be used to directly observe the chemical responses of V. cholerae biofilm colonies to treatment with TCA. A major challenge of MALDI-IMS is optimizing the sample preparation and drying for a particular growth condition and microbial strain. Here we demonstrate how V. cholerae is cultured and prepared for MALDI-IMS analysis and highlight critical steps to ensure proper sample adherence to a MALDI target plate and maintain spatial distributions when applying this technique to any microbial strain. We additionally show how to use both manual interrogation and statistical analyses of MALDI-IMS data to establish the adequacy of the sample preparation protocol. This protocol can serve as a guideline for the development of sample preparation techniques and the acquisition of high quality MALDI-IMS data.
    Keywords:  Imaging mass spectrometry; Matrix-assisted laser desorption/ionization; Microbial biofilm
    DOI:  https://doi.org/10.1016/bs.mie.2021.11.014
  35. Analyst. 2022 Apr 07.
    Establishing a quantitative fluorescence assay for the rapid detection of kynurenine in urine.
    Kamlesh Patel, Marcos Fernandez-Villamarin, Craig Ward, Janet M Lord, Peter Tino, Paula M Mendes.
      The kynurenine metabolite is associated with many diseases and disorders, ranging from diabetes and sepsis to more recently COVID-19. Here we report a fluorescence-based assay for the detection of kynurenine in urine using a specific chemosensor, 3-formyl-4-(ethylthio)-7-(diethylamino)-coumarin. The assay produces a linear response at clinically relevant ranges (1-20 μM), with a limit of detection of 0.7 μM. The average standard addition recoveries of kynurenine in synthetic urine samples are near to 100%, and the relative standard deviation values are less than 8%. The established fluorescence assay for quantitative analysis of kynurenine in urine is facile, sensitive and accurate and holds great potential for low-cost and high-throughput analysis of kynurenine in clinical laboratory settings.
    DOI:  https://doi.org/10.1039/d2an00107a
  36. J Chromatogr A. 2022 Mar 28. pii: S0021-9673(22)00204-7. [Epub ahead of print]1671 463006
    Analytical method to monitor contaminants of emerging concern in water and soil samples from a non-conventional wastewater treatment system.
    Blanca Huidobro-López, Isabel López-Heras, Covadonga Alonso-Alonso, Virtudes Martínez-Hernández, Leonor Nozal, Irene de Bustamante.
      Nonconventional wastewater treatments, such as vegetation filters (VFs), are propitious systems to attenuate contaminants of emerging concern (CECs) in small municipalities. The development of standardised multiresidue and multimatrix methods suitable for measuring a reliable number of CEC in environmental samples is crucial for monitoring infiltrating concentrations and for ensuring these systems' treatment capacity. The objective of this study is to develop and validate an analytical method for the simultaneous determination of CECs, including transformation products (TPs), with diverse physico-chemical properties, in environmental samples. The optimised method is based on sample clean-up and preconcentration by solid-phase extraction (SPE), followed by liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). The method is able to detect and quantify 40 target CECs, including pharmaceuticals of different classes (analgesics, antibiotics, antihypertensives, lipid regulators, anticonvulsants, antidepressants, antiarrhythmics, beta-blockers, amongst others), hormones and lifestyle products with good reproducibility (variations below 23%), in different water matrices, and 28 CECs, in soil samples. Acceptable recoveries (65-120%) were obtained for most of the CECs in all the matrices. However in the soil samples, as complexity required a prior extraction treatment, the recovery of some analytes was affected, which reduced the number of target CECs. The achieved methodological quantification limits (0.05-5 ng/L and 0.04-1.1 ng/g levels for the water and the soil matrices, respectively) were reasonably low for most CECs. The proposed method was successfully applied to monitor CECs in a VF. The CECs detected at higher concentrations are some of the world's most widely used products (e.g. acetaminophen or caffeine and its main TP, paraxanthine). The results showed an almost 70% reduction in CEC concentrations during infiltration. The groundwater data indicated that the VF treatment operation did not affect the underlying aquifer (Cmax found in GW <1 µg/L).
    Keywords:  Contaminants of emerging concern; Liquid chromatography-tandem mass spectrometry; Non-conventional wastewater treatments; Solid-phase extraction; Vegetation filter; Water and soil matrices
    DOI:  https://doi.org/10.1016/j.chroma.2022.463006
  37. Anal Methods. 2022 Apr 06.
    Advanced tuning of the ion management parameters in GC × GC-HRMS using a Fourier transform Orbitrap mass analyzer for pixel-based data handling and multivariate analysis.
    Amilton Moreira de Oliveira, Carlos Alberto Teixeira, Leandro Wang Hantao.
      GC × GC investigations are well known to generate a substantial amount of information-rich and structurally complex data, requiring advanced data processing strategies like chemometrics. Many workflows are available for data handling and processing, such as the peak-table and pixel-based approaches. The goal of this work is to present a solution based on method development to solve the missing pixel problem that may be encountered in experiments performed with GC and GC × GC coupled to the Fourier transform orbital ion trap (FT-Orbitrap) mass analyzer. Data input is vital for pixel-based chemometric analyses, as some post-processing solutions may lead to significant loss of chemical information in the data set. Hence, a key requisite is that the chemical information is consistently indexed in the data arrays for proper pixel-based data handling and analysis. In this study, we carefully evaluated the ion management parameters to preserve the intrinsic structure and information of the data arrays of the GC × GC-FT-Orbitrap for future pixel-oriented chemometric analysis. The most acceptable conditions yielded acquisition rates up to 42.6 spectra per s, while a routine setting of 24.7 Hz was successfully employed in analyses of different petroleum fractions, producing both consistent tensor sizes and acceptable peak reconstructions. A data acquisition rate of 24.7 spectra per s and a mass resolving power of 15 000 allowed the resolution of a mass split of only 0.004 Da - which is an interesting configuration for challenging applications in petroleomics. Using such advanced settings, the missing pixel problem was reduced from up to 30% to much less than 0.04% of the data array dimension. Thus, the proposed configuration can be employed in studies that require pixel-oriented multivariate data analysis.
    DOI:  https://doi.org/10.1039/d2ay00314g
  38. Front Genet. 2022 ;13 854752
    Unsupervised Multi-Omics Data Integration Methods: A Comprehensive Review.
    Nasim Vahabi, George Michailidis.
      Through the developments of Omics technologies and dissemination of large-scale datasets, such as those from The Cancer Genome Atlas, Alzheimer's Disease Neuroimaging Initiative, and Genotype-Tissue Expression, it is becoming increasingly possible to study complex biological processes and disease mechanisms more holistically. However, to obtain a comprehensive view of these complex systems, it is crucial to integrate data across various Omics modalities, and also leverage external knowledge available in biological databases. This review aims to provide an overview of multi-Omics data integration methods with different statistical approaches, focusing on unsupervised learning tasks, including disease onset prediction, biomarker discovery, disease subtyping, module discovery, and network/pathway analysis. We also briefly review feature selection methods, multi-Omics data sets, and resources/tools that constitute critical components for carrying out the integration.
    Keywords:  clustering method; data-ensemble; model-ensemble; multi-omics; network analysis; sequential analysis; unsupervised integration
    DOI:  https://doi.org/10.3389/fgene.2022.854752
  39. J Chromatogr Sci. 2022 Apr 02. pii: bmac022. [Epub ahead of print]
    Quantification of Ephedrine Substances in Human Urine by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.
    Yunfei Wang, Kuan Yan, Zhanliang Wang, Genye He, Wei Chang.
      An accurate quantitative method for four prohibited ephedrine substances in human urine has been established, based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The quantitative bias caused by pretreatment operations and matrix effects was reduced by the dilute and shoot pretreatment method. The good separation of isomers was achieved with the advantages of the UPLC instrument and Agilent Poroshell 120 EC-C8 UPLC column. Stable quantitative ions were selected during the analysis with MS/MS. The result of the method validation experiment showed an excellent linearity between 50% and 200% threshold concentration with a correlation coefficient (r2) greater than 0.999. The coefficient of variation at the limit of quantification and threshold was <20% and 10%, respectively. The uncertainty was below the maximum uncertainty specified in the technical document of the World Anti-Doping Agency (WADA). The analytical result using this method has passed the WADA-external quality assessment scheme. The anti-doping laboratory has applied the method in routine tests and reported adverse analytical finding.
    DOI:  https://doi.org/10.1093/chromsci/bmac022
  40. J Agric Food Chem. 2022 Apr 07.
    Rapid and One-Step Screening of Taxane Compounds by a Two-Dimensional Carbon Microfiber Fractionation System Combined with Tandem Mass Spectrometry.
    Zhao Wang, Meiyu Cui, Biao Ma, Lei Yang, Yingli Yu, Haiyan Cui, Dongri Jin, Haibo Shang, Donghao Li.
      Taxane compounds have attracted wide attention due to the basic chemical structure of taxol as an alternative anticancer drug. The full-scan tandem mass spectrometry (MS/MS) fragmentation behaviors of seven taxane compounds were studied. For taxanes of Sc-T and Sc-T-Xyl types, diagnostic product ions are originated from a cleavage in the ester bond of the C13 position and the C-O bond of the C7 position, and the subsequent fragmentation pattern is similar to those of M-type taxanes with the loss of different numbers of acetic acid moieties (AcOH), benzoic acid moieties (BzOH), and H2O molecules. A rapid (7 min) and one-step screening method of two-dimensional microscale carbon fiber and active carbon fiber columns combined with tandem mass spectrometry (2DμCFs-MS/MS) was developed for the screening of taxane compounds from Taxus cuspidata samples. Before MS/MS analysis, the 2DμCFs system can group the sample extract without any pretreatment into three chromatographic-type fractions of strong, medium, and weak polarity to avoid matrix interference, such as lipids and pigments. The 2DμCFs-MS/MS can also conduct qualitative and quantitative analysis of taxane compounds, which is evaluated by limits of detection ranging from 3 to 50 ng mL-1, limits of quantitation ranging from 10 to 150 ng mL-1, satisfactory recoveries from 75.2 to 112.2%, and reproducibilities with relative standard deviations from 1.4 to 11.7%.
    Keywords:  2DμCFs; Taxus cuspidata; rapid and one-step screening; taxane
    DOI:  https://doi.org/10.1021/acs.jafc.2c00573
  41. Front Psychiatry. 2022 ;13 802710
    Alterations in the Plasma Lipidome of Adult Women With Bipolar Disorder: A Mass Spectrometry-Based Lipidomics Research.
    Lin Guo, Ting Zhang, Rui Li, Zhi-Quan Cui, Jing Du, Jia-Bin Yang, Fen Xue, Yi-Huan Chen, Qing-Rong Tan, Zheng-Wu Peng.
      Lipidomics has become a pivotal tool in biomarker discovery for the diagnosis of psychiatric illnesses. However, the composition and quantitative analysis of peripheral lipids in female patients with bipolar disorder (BD) have been poorly addressed. In this study, plasma samples from 24 female patients with BD and 30 healthy controls (HCs) were analyzed by comprehensive lipid profiling and quantitative validation based on liquid chromatography-mass spectrometry. Clinical characteristics and a correlation between the level of lipid molecules and clinical symptoms were also observed. We found that the quantitative alterations in several lipid classes, including acylcarnitine, lysophosphatidylethanolamine, GM2, sphingomyelin, GD2, triglyceride, monogalactosyldiacylglycerol, phosphatidylinositol phosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylethanolamine, phosphatidylserine, and lysophosphatidylinositol, were remarkably upregulated or downregulated in patients with BD and were positively or negatively correlated with the severity of psychotic, affective, or mania symptoms. Meanwhile, the composition of different carbon chain lengths and degrees of fatty acid saturation for these lipid classes in BD were also different from those of HCs. Moreover, 55 lipid molecules with significant differences and correlations with the clinical parameters were observed. Finally, a plasma biomarker set comprising nine lipids was identified, and an area under the curve of 0.994 was obtained between patients with BD and the HCs. In conclusion, this study provides a further understanding of abnormal lipid metabolism in the plasma and suggests that specific lipid species can be used as complementary biomarkers for the diagnosis of BD in women.
    Keywords:  bipolar disorder; healthy controls; lipidomics; plasma; women
    DOI:  https://doi.org/10.3389/fpsyt.2022.802710
  42. Rapid Commun Mass Spectrom. 2022 Apr 05.
    Why tandem mass spectrometry for trace analysis: concepts of tandem analytical techniques.
    Richard A Yost.
      The triple quadrupole mass spectrometer, typically in combination with a gas or liquid chromatograph (GC/MS/MS and LC/MS/MS), is perhaps the most iconic example today of a tandem analytical instrument. Whenever I present a lecture on these instrumental techniques, I spend some time talking about the concepts of such tandem or hyphenated techniques for trace analysis (that is, the detection and/or quantitation of one or more analytes present in a mixture at low levels). Often, I find that many practitioners of these techniques have never spent much time thinking about the fundamental principles and basic concepts. So here I present a tutorial on the principles of tandem trace analytical techniques such as GC/MS/MS and LC/MS/MS. The topics include the capabilities and requirements for such tandem techniques, the role of sensitivity and selectivity in tandem techniques, ways to assess the "informing power" of these techniques, and a comparison of tandem techniques to individual techniques at high resolution. I have illustrated these points with several examples of trace analysis using tandem analytical techniques.
    DOI:  https://doi.org/10.1002/rcm.9310
  43. J Biomol NMR. 2022 Apr 07.
    Fundamental and practical aspects of machine learning for the peak picking of biomolecular NMR spectra.
    Da-Wei Li, Alexandar L Hansen, Lei Bruschweiler-Li, Chunhua Yuan, Rafael Brüschweiler.
      Rapid progress in machine learning offers new opportunities for the automated analysis of multidimensional NMR spectra ranging from protein NMR to metabolomics applications. Most recently, it has been demonstrated how deep neural networks (DNN) designed for spectral peak picking are capable of deconvoluting highly crowded NMR spectra rivaling the facilities of human experts. Superior DNN-based peak picking is one of a series of critical steps during NMR spectral processing, analysis, and interpretation where machine learning is expected to have a major impact. In this perspective, we lay out some of the unique strengths as well as challenges of machine learning approaches in this new era of automated NMR spectral analysis. Such a discussion seems timely and should help define common goals for the NMR community, the sharing of software tools, standardization of protocols, and calibrate expectations. It will also help prepare for an NMR future where machine learning and artificial intelligence tools will be common place.
    Keywords:  Deep learning; Deep neural network; Machine learning; NMR spectroscopy; Peak picking; Spectral analysis
    DOI:  https://doi.org/10.1007/s10858-022-00393-1
  44. Environ Monit Assess. 2022 Apr 06. 194(5): 328
    Development and validation of dispersive liquid-liquid microextraction method for the determination of 15 polycyclic aromatic hydrocarbons in 200 Antarctica samples by gas chromatography mass spectrometry.
    Maral Selin Fındıkoğlu Ercan, Merve Fırat Ayyıldız, Elif Yazıcı, Berfin Metin, Dotse Selali Chormey, Elif Seda Koçoğlu, Sezgin Bakırdere.
      Antarctica has seen an increase in scientific research and tourism, and anthropogenic activities such as incineration of waste products and fuel combustion for energy and transportation are potential contamination sources to the ecosystem. Polycyclic aromatic hydrocarbons are common products of incomplete combustion of organic compounds and could be among accumulating contaminants in Antarctica. Thus, this study sought to develop a sensitive dispersive liquid-liquid microextraction method for the determination of 15 polycyclic aromatic hydrocarbons by gas chromatography mass spectrometry. Parameters that were relevant to the extraction method were carefully optimized and validated using aqueous standard solutions. The optimum method recorded detection limits in the range of 0.20-6.1 µg/L for the analytes. Spike recovery experiments were carried out on artificial seawater, rock-soil, and moss samples, using matrix matching calibration to mitigate effects of the sample matrices. The samples analyzed included seawater, lake, rock-soil, moss, seaweed, and feces samples all collected from the Horseshoe and Faure Islands in Antarctica. The percent recovery results obtained for the samples spiked at different concentrations ranged between 86 and 115%.
    Keywords:  Antarctica; Gas chromatography mass spectrometry (GC–MS); Matrix matching calibration; Microextraction; Polycyclic aromatic hydrocarbon (PAH)
    DOI:  https://doi.org/10.1007/s10661-022-09991-w
  45. Drug Test Anal. 2022 Apr 02.
    Quantification of thyroid hormones and analogs by liquid chromatography coupled to mass spectrometry. Preliminary results in athletes and non-athletes serum samples.
    Dayamin Martínez Brito, Patrizia Leogrande, Francesco Donati, Xavier de la Torre, Francesco Botrè.
      This paper aimed to assess a method to measure eight thyroid-related compounds in serum by liquid chromatography-mass spectrometry (LC-MS/MS), to verify the correlation with radioimmunoassay (RIA), to evaluate the possible cross-reactivity and, to observe differences between athletes declaring the consumption of sodium levothyroxine and non-athletes serum samples. Validation was carried out to assess carryover, working range and linearity, limit of detection and limit of quantification, precision, matrix influence, recovery, accuracy, and uncertainty. Comparisson between RIA and LC-MS/MS results were done. The assay was applied to serum samples and comparison with RIA was done for T3 and T4 levels supported by RIA TSH measurements. Validation parameters showed satisfactory results. Correlation between RIA and LC-MS/MS for T3 and T4 showed good results but a cross-reactivity between T3 and T3AA was observed. Although no significant differences were proved, preliminary comparison between athletes and non-athletes serum samples showed a shift towards high values of TSH and lower for T4 values in the athletes' group. Differences between thyronine and T4AA concentrations and ratios were observed. The trend of T4 values supported by TSH measures might indicate subclinical hypothyroidism in athletes. This represents one of the most controversial thyroid statuses as different criteria about its treatment are described, especially since one of the exogenous causes is inadequate levothyroxine therapy. Because the variation of thyroid hormones and TSH have been extensively studied in high-performance sports, it is worth considering the need to set an adequate reference interval to accurately assess the thyroid status in athletes.
    Keywords:  LC-MS/MS; RIA; sport performance; thyroid hormones; thyronacetic acids; thyronine; validation
    DOI:  https://doi.org/10.1002/dta.3269
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