bims-metlip 2023-04-23 papers

bims-metlip

Biomed News

on Methods and protocols in metabolomics and lipidomics

Issue of 2023–04–23
thirty papers selected by
Sofia Costa, Matterworks

Comparison of chromatographic conditions for the targeted tandem mass spectrometric determination of 354 mammalian metabolites.
Structural elucidation of 3-nitrophenylhydrazine derivatives of tricarboxylic acid cycle acids and optimization of their fragmentation to boost sensitivity in liquid chromatography-mass spectrometry.
LipidOz enables automated elucidation of lipid carbon-carbon double bond positions from ozone-induced dissociation mass spectrometry data.
3D-MSNet: A point cloud based deep learning model for untargeted feature detection and quantification in profile LC-HRMS data.
Simultaneous quantification of fatty acids in serum with dual derivatization by Liquid Chromatography-Tandem Mass Spectrometry.
Extractive-liquid sampling electron ionization-mass spectrometry (E-LEI-MS): a new powerful combination for direct analysis.
SmartGate is a spatial metabolomics tool for resolving tissue structures.
Single-Filament Imaging Mass Spectrometry Lipidomics in Arthrospira platensis.
Development and validation of a simple HPLC-MS/MS method for the quantification of methylmalonic acid without a derivatization step in human serum.
Validated LC-MS/MS method for determination of paxalisib in mouse plasma: An application to pharmacokinetic study in mice.
A rapid and sensitive LC-MS/MS method for simultaneous determination of melphalan and its monohydroxy and dihydroxy metabolites in human plasma.
Determination of Ruboxistaurin analysis in rat plasma utilizing LC-MS/MS technique.
Simultaneous determination of four antibiotics in human plasma by high-performance LC-MS/MS: application to therapeutic drug monitoring.
[Determination of amantadine, rimantadine and dimethylamantadine residues in poultry by ultra-performance liquid chromatography-tandem mass spectrometry].
Gaussian Mixture Modeling Extensions for Improved False Discovery Rate Estimation in GC-MS Metabolomics.
Determination of olverembatinib in human plasma and cerebrospinal fluid by an LC-MS/MS method: Validation and clinical application.
Analytical Techniques for Single-Cell Biochemical Assays of Lipids.
Expeditious quantification of plasma tacrolimus with liquid chromatography tandem mass spectrometry in solid organ transplantation.
[Determination of three furfural compounds in coffee and coffee products by gas chromatography-tandem mass spectrometry with internal standard isotope].
A novel smartphone HPTLC assaying platform versus traditional densitometric method for simultaneous quantification of alfuzosin and solifenacin in their dosage forms as well as monitoring content uniformity and drug residues on the manufacturing equipment.
LC-MS/MS method for the quantitation of OCT1 biomarker isobutyrylcarnitine in human plasma with clinical sample analysis.
Analysis of 10 phthalate esters in water-based adhesives by supercritical fluid chromatography-tandem mass spectrometry combined with spherical carbons-based dispersion solid-phase extraction.
Simultaneous Determination of Rifamycin Antibiotics and Their Active Metabolites in Human Plasma Using UHPLC-MS/MS to Evaluate Their Impact on Target Peak Concentrations: A Short Communication.
Efficient Sample Preparation System for Multi-Omics Analysis via Single Cell Mass Spectrometry.
Analytical methods for the analysis of volatile natural products.
XAI-enabled neural network analysis of metabolite spatial distributions.
Rapid and Direct Assessment of Asphalt Volatile Organic Compound Emission Based on Carbon Fiber Ionization Mass Spectrometry.
What about nitrogen? Using nitrogen as a carrier gas during the analysis of petroleum biomarkers by gas chromatography mass spectrometry.
Isolation and Mass Spectrometry-Based Profiling of Major Lipids in Brown Adipose Tissue.
An Antiviral Drug-Peramivir: Degradation and Identification of Impurities and the Endorsement of HPLC-MS Method.

J Chromatogr A. 2023 Apr 09. pii: S0021-9673(23)00211-X. [Epub ahead of print]1697 463985

Comparison of chromatographic conditions for the targeted tandem mass spectrometric determination of 354 mammalian metabolites.

Dimitrios J Floros, Kangkang Xu, Franz Berthiller, Heidi Schwartz-Zimmermann.

  Metabolomics is becoming increasingly popular in livestock research, but no single analytical method can cover the entire metabolome. As such, we compared similar and complementary chromatographic methods with respect to analyte coverage and chromatographic properties of mammalian metabolites. We investigated 354 biologically relevant primary metabolites from 19 compound classes including amino acids, bile acids, biogenic amines, carboxylic acids, lipids, nucleotides and sugars. A total of 2063 selected reaction monitoring transitions were optimized on a triple quadrupole mass spectrometer. We then determined the retention profiles and peak parameters of our compounds using an anion exchange chromatography (AIC), three reversed-phase (RP) and three hydrophilic interaction liquid chromatography (HILIC) methods. On average, HILIC methods covered 54% of all metabolites with retention factors >1, while average RP coverage was 41%. In contrast to RP, HILIC methods could also retain polar metabolites such as amino acids and biogenic amines. Carboxylic acids, nucleotides, and sugar related compounds were best separated by AIC or zwitterionic pHILIC with alkaline eluents. Combining two complementary HILIC and RP methods increased the library coverage to 92%. By further including important short chain fatty acids, a combination of HILIC, RP and AIC methods achieved a coverage of 97%. The resulting dataset of LC and MS/MS parameters will facilitate the development of tailor-made quantitative targeted LC-MS/MS methods to investigate the mammalian metabolome.

Keywords:  Anion-exchange chromatography; HILIC; LC-MS/MS; Metabolomics; Reversed phase chromatography

DOI:  https://doi.org/10.1016/j.chroma.2023.463985
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Apr 11. pii: S1570-0232(23)00129-0. [Epub ahead of print]1222 123719

Structural elucidation of 3-nitrophenylhydrazine derivatives of tricarboxylic acid cycle acids and optimization of their fragmentation to boost sensitivity in liquid chromatography-mass spectrometry.

Ondřej Hodek, John Henderson, Lidia Argemi-Muntadas, Adnan Khan, Thomas Moritz.

  Carboxylic acids participate in many metabolic pathways including tricarboxylic acid (TCA) cycle. Therefore, there have been ongoing attempts to develop sensitive liquid chromatography-mass spectrometry methods over the last decades. Derivatization of the carboxylic acids with 3-nitrophenylhydrazine presents a well-established methodology, and yet the derivatized species of polycarboxylic acids and their fragmentation in collision-induced dissociation have not been fully studied before. In our study, we elucidated how annotation of most abundant 3-nitrophenylhydrazine derivatives and optimization of their fragmentation in multiple reaction monitoring can boost the sensitivity, especially for polycarboxylic acids. Finally, the optimized liquid chromatography-tandem mass spectrometry method allowed for low detection limits ranging from 10 pM for 2-oxoglutaric acid to 800 pM for pyruvic acid. All TCA carboxylates were quantified in 20 µL of human plasma and the targeted method was validated in the same matrix. The same methodology with a modified gradient elution was also applied to untargeted screening of fatty acids by using high-resolution mass spectrometry enabling identification of 29 medium- to long-chain fatty acids in human plasma. The TCA carboxylates were also quantified in 105 of C2C12 mouse myuotube cells grown under different treatments to proof applicability of the methodology to biological studies in a wider sense. However, unfortunately all the TCA carboxylates were also found in the derivatized blanks in substantial amounts, which prevents from using the methodology for quantification of the carboxylates in less than 105 cells.

Keywords:  3-nitrophenylhydrazine; Carboxylic acid; Derivatization; Liquid chromatography-mass spectrometry

DOI:  https://doi.org/10.1016/j.jchromb.2023.123719
Commun Chem. 2023 Apr 19. 6(1): 74

LipidOz enables automated elucidation of lipid carbon-carbon double bond positions from ozone-induced dissociation mass spectrometry data.

Dylan H Ross, Joon-Yong Lee, Aivett Bilbao, Daniel J Orton, Josie G Eder, Meagan C Burnet, Brooke L Deatherage Kaiser, Jennifer E Kyle, Xueyun Zheng.

Lipids play essential roles in many biological processes and disease pathology, but unambiguous identification of lipids is complicated by the presence of multiple isomeric species differing by fatty acyl chain length, stereospecifically numbered (sn) position, and position/stereochemistry of double bonds. Conventional liquid chromatography-mass spectrometry (LC-MS/MS) analyses enable the determination of fatty acyl chain lengths (and in some cases sn position) and number of double bonds, but not carbon-carbon double bond positions. Ozone-induced dissociation (OzID) is a gas-phase oxidation reaction that produces characteristic fragments from lipids containing double bonds. OzID can be incorporated into ion mobility spectrometry (IMS)-MS instruments for the structural characterization of lipids, including additional isomer separation and confident assignment of double bond positions. The complexity and repetitive nature of OzID data analysis and lack of software tool support have limited the application of OzID for routine lipidomics studies. Here, we present an open-source Python tool, LipidOz, for the automated determination of lipid double bond positions from OzID-IMS-MS data, which employs a combination of traditional automation and deep learning approaches. Our results demonstrate the ability of LipidOz to robustly assign double bond positions for lipid standard mixtures and complex lipid extracts, enabling practical application of OzID for future lipidomics.

DOI: https://doi.org/10.1038/s42004-023-00867-9
Bioinformatics. 2023 Apr 18. pii: btad195. [Epub ahead of print]

3D-MSNet: A point cloud based deep learning model for untargeted feature detection and quantification in profile LC-HRMS data.

Ruimin Wang, Miaoshan Lu, Shaowei An, Jinyin Wang, Changbin Yu.

MOTIVATION: Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is widely used in composition profiling in untargeted metabolomics research. While retaining complete sample information, mass spectrometry (MS) data naturally have the characteristics of high dimensionality, high complexity, and huge data volume. In mainstream quantification methods, none of the existing methods can perform direct three-dimensional analysis on lossless profile MS signals. All software simplifies calculations by dimensionality reduction or lossy grid transformation, ignoring the full three-dimensional signal distribution of mass spectrometry data and resulting in inaccurate feature detection and quantification.
RESULTS: On the basis that the neural network is effective for high-dimensional data analysis and can discover implicit features from large amounts of complex data, in this work, we propose 3D-MSNet, a novel deep-learning-based model for untargeted feature extraction. 3D-MSNet performs direct feature detection on three-dimensional MS point clouds as an instance segmentation task. After training on a self-annotated 3D feature dataset, we compared our model with 9 popular software (MS-DIAL, MZmine 2, XCMS Online, MarkerView, Compound Discoverer, MaxQuant, Dinosaur, DeepIso, PointIso) on two metabolomics and one proteomics public benchmark datasets. Our 3D-MSNet model outperformed other software with significant improvement in feature detection and quantification accuracy on all evaluation datasets. Furthermore, 3D-MSNet has high feature extraction robustness and can be widely applied to profile MS data acquired with various high-resolution mass spectrometers with various resolutions.
AVAILABILITY: 3D-MSNet is open-source and freely available at https://github.com/CSi-Studio/3D-MSNet under a permissive license. Benchmark datasets, training dataset, evaluation methods and results are available at https://doi.org/10.5281/zenodo.6582912.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

DOI: https://doi.org/10.1093/bioinformatics/btad195
J Sep Sci. 2023 Apr 19. e2300003

Simultaneous quantification of fatty acids in serum with dual derivatization by Liquid Chromatography-Tandem Mass Spectrometry.

Zhibo Fu, Xuefeng Xu, Chuhui Lin, Haoyu Yang, Linghao Zhao, Yuanyuan Zhou, Yanbin Song, Min Zhang, Hongyang Zhang, Ping Hu.

  Fatty acids have multitudinous biological functions and play a crucial role in many biological processes, but due to poor ionization efficiency and lack of appropriate internal standard, the comprehensive quantification of fatty acids by liquid chromatography-tandem mass spectrometry is still challenging. In this study, a new, accurate and reliable method for quantifying 30 fatty acids in serum using dual derivatization was proposed. Indole-3-acetic acid hydrazide derivants of fatty acids were used as the internal standard and Indole-3-carboxylic acid hydrazide derivants of them were used to quantify. The derivatization conditions were systematically optimized and the method validation results showed a good linearity with R2 > 0.9942, low detection limit (0.03-0.6 nM), precision (1.6% - 9.8% for intra-day and 4.6% - 14.1% for inter-day), recovery (88.2% - 107.2% with RSD < 10.5%), matrix effect (88.3% - 105.2% with the RSD < 9.9%) and stability (3.4% - 13.8% for fatty acids derivants in 24 h at 4°C and 4.2% - 13.8% for three freeze-thaw cycles). Finally, this method was successfully applied to quantify fatty acids in serum samples of Alzheimer's patients. In contrast to the healthy control group, nine fatty acids showed a significant increase in the Alzheimer's disease group. This article is protected by copyright. All rights reserved.

Keywords:  Dual derivatization; Fatty acids; Indole-3-acetic acid hydrazide; Indole-3-carboxylic acid hydrazide; Liquid Chromatography-Tandem Mass Spectrometry

DOI:  https://doi.org/10.1002/jssc.202300003
Sci Rep. 2023 Apr 20. 13(1): 6429

Extractive-liquid sampling electron ionization-mass spectrometry (E-LEI-MS): a new powerful combination for direct analysis.

Adriana Arigò, Giorgio Famiglini, Nicole Marittimo, Marco Agostini, Caterina Renzoni, Pierangela Palma, Achille Cappiello.

One of modern analytical chemistry main challenges is providing as fast as possible results in different application fields. In this view, real-time analysis techniques are experiencing ever-increasing success as they can provide data quickly, almost without sample preparation steps. Most of real-time approaches are based on direct mass spectrometry (DMS), a method of analyzing samples without the need for separation or pre-treatment steps. Instead, the sample is directly introduced into the mass spectrometer for analysis. In this context, ambient ionization mass spectrometry (AIMS) techniques are widely represented and successfully used. Extractive-liquid sampling electron ionization-mass spectrometry (E-LEI-MS) represents a different analytical strategy that allows coupling ambient sampling with electron ionization (EI), avoiding any sample preparation step and providing identification based on the comparison with the National Institute of Standards and Technology (NIST) library spectra. E-LEI-MS consists of a dispositive for solvent release and sampling at ambient conditions coupled with an EI source of a single quadrupole mass spectrometer. A micromanipulator allows fine (x,y,z) positioning of a sampling tip. MS can operate in scan or SIM modes depending on the application goals and requirements. Several preliminary successful results were already obtained due to the highly informative EI mass spectra generation. The system was applied to the analysis of active ingredients in pharmaceutical tablets, pesticides on fruit peel, a drug of abuse (cocaine) determination in banknotes, and analysis of unknown components on painting surfaces. Both forensic and artwork applications allowed determining the spatial distribution of the analytes. Here we present a proof-of-concept of E-LEI-MS for targeted/non-targeted analysis and semi-quantitative detection.

DOI: https://doi.org/10.1038/s41598-023-33647-5
Brief Bioinform. 2023 Apr 17. pii: bbad141. [Epub ahead of print]

SmartGate is a spatial metabolomics tool for resolving tissue structures.

Kaixuan Xiao, Yu Wang, Kangning Dong, Shihua Zhang.

  Imaging mass spectrometry (IMS) is one of the powerful tools in spatial metabolomics for obtaining metabolite data and probing the internal microenvironment of organisms. It has dramatically advanced the understanding of the structure of biological tissues and the drug treatment of diseases. However, the complexity of IMS data hinders the further acquisition of biomarkers and the study of certain specific activities of organisms. To this end, we introduce an artificial intelligence tool, SmartGate, to enable automatic peak selection and spatial structure identification in an iterative manner. SmartGate selects discriminative m/z features from the previous iteration by differential analysis and employs a graph attention autoencoder model to perform spatial clustering for tissue segmentation using the selected features. We applied SmartGate to diverse IMS data at multicellular or subcellular spatial resolutions and compared it with four competing methods to demonstrate its effectiveness. SmartGate can significantly improve the accuracy of spatial segmentation and identify biomarker metabolites based on tissue structure-guided differential analysis. For multiple consecutive IMS data, SmartGate can effectively identify structures with spatial heterogeneity by introducing three-dimensional spatial neighbor information.

Keywords:  automatic peak picking; imaging mass spectrometry; spatial metabolomics; spatial segmentation

DOI:  https://doi.org/10.1093/bib/bbad141
Rapid Commun Mass Spectrom. 2023 Apr 16. e9525

Single-Filament Imaging Mass Spectrometry Lipidomics in Arthrospira platensis.

Kaitlin C Lesco, Steven M Rowland, S Kim Ratanathanawongs Williams, Lieve M L Laurens.

RATIONALE: Elucidating intra-organismal biochemical and lipid organization in photosynthetic biological cell factories of filamentous cyanobacteria, i.e., Arthrospira platensis (Spirulina), is important to track physiological response mechanisms during growth. Little is known about the filaments' biochemical organization and cellular structure and no label-free imaging techniques exist that provide molecular mapping.
METHODS: We applied ultra-high resolution mass spectrometry (7T FT-ICR-MS) matrix-assisted laser desorption ionization (MALDI) imaging to immobilized Spirulina filaments to investigate the localization of lipids across distinct physiological regions. We optimized matrix selection and deposition methods with the goal of facilitating high spatial, and intra-filament, resolution using untargeted multivariate statistical spectral deconvolution across MS pixels.
RESULTS: Our results demonstrate an improved two step application with an optimized procedure for intra-organismal lipid profiling to improve analyte sensitivity and achieve higher spatial resolution, whereby we evaluate three conventional matrices 2,5-dihydroxybenzoic acid (DHB), a 9:1 ratio of DHB:superDHB (sDHB), 1,5- diaminonaphthalene (DAN) and a 50:50 mix of DHB:sDHB and compare delineation and pixel-based elucidation of intra-filament lipidomics. We identified a total of 1,626 features that could be putatively assigned a lipid-like formula based on database query and 46 unique features, with associated lipid assignments that were significantly distinct in their intra-filament location.
CONCLUSIONS: MALDI- imaging MS with untargeted statistical spectral deconvolution was used to visualize intra-filament lipidomics organization in Spirulina filaments. Improvements in matrix deposition, including sequential sublimation and pneumatic spraying, increased signal abundance at high spatial resolution and allowed for identification of distinct lipid composition regions. This work outlines a methodology that may be used for micro-ecological untargeted molecular phenotyping.

DOI: https://doi.org/10.1002/rcm.9525
Biomed Chromatogr. 2023 Apr 17. e5657

Development and validation of a simple HPLC-MS/MS method for the quantification of methylmalonic acid without a derivatization step in human serum.

Sabrina Hofmann, Julian Gebauer, Dušan Krnáč, Anja Prantz, Katarína Reiffová, Boris Rolinski, Rastislav Serbin.

  A simple and rapid HPLC-MS/MS analytical method was developed and validated for the determination of methylmalonic acid without a derivatization step in human serum. Serum samples with a volume of 200 μL were pre-treated in a simple way based on ultrafiltration using a VIVASPIN 500 ultrafiltration column. Chromatographic separation was achieved on a Luna Omega C18 column with a PS C18 precolumn guard by a gradient elution using 0.1% (v/v) formic acid in water (component A of the mobile phase) and 0.5% (v/v) formic acid in acetonitrile (component B of the mobile phase) with flow rate 0.2 ml.min-1 . The total run time of the analysis was 4.5 minutes. Negative electrospray ionization and multiple reaction monitoring mode were used. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for methylmalonic acid were determined to be 13.6 nmol. L-1 and 42.3 nmol. L-1 , respectively. The developed method allows the quantification of methylmalonic acid in a wide linear range of 42.3-4230 nmol. L-1 with a correlation coefficient of 0.9991.

Keywords:  HPLC-MS/MS; Methylmalonic acid; human serum; ultrafiltration; vitamin B12 deficiency

DOI:  https://doi.org/10.1002/bmc.5657
Biomed Chromatogr. 2023 Apr 17. e5650

Validated LC-MS/MS method for determination of paxalisib in mouse plasma: An application to pharmacokinetic study in mice.

A B Vinod, Arunava Das.

  A sensitive and rapid LC-MS/MS method has been developed and validated for the quantification of paxalisib in mouse plasma. Liquid-liquid extraction method was used for the extraction of paxalisib and filgotinib (internal standard, IS) from mouse plasma. A clean chromatographic separation of paxalisib and the IS was achieved on an Atlantis dC18 column using an isocratic mobile phase (10 mM ammonium formate and acetonitrile; 30:70%, v/v) delivered at a flow rate of 0.7 mL/min. The total run time was 2.5 min. Paxalisib and filgotinib were eluted at 1.21 and 0.94 min, respectively. The MS/MS transitions monitored were m/z 383.25→309.20 and 426.30→291.20 for paxalisib and filgotinib, respectively. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The method was proved to be accurate and precise at a linearity range of 1.39-2287 ng/mL. The intra- and inter-day precision for paxalisib in mouse plasma were in the range of 1.42-9.61 and 4.70-9.63%, respectively. Paxalisib was stable in a series of stability conditions. Post-oral administration to mice, paxalisib maximum plasma concentrations were attained at 2.0 h. Paxalisib half-life ranged between 3.2-4.2 h. Paxalisib exhibited low clearance and moderate volume of distribution. Oral bioavailability was 71%.

Keywords:  LC-MS/MS; Paxalisib; filgotinib; method validation; mouse plasma; pharmacokinetics

DOI:  https://doi.org/10.1002/bmc.5650
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Apr 06. pii: S1570-0232(23)00108-3. [Epub ahead of print]1222 123698

A rapid and sensitive LC-MS/MS method for simultaneous determination of melphalan and its monohydroxy and dihydroxy metabolites in human plasma.

Sanwang Li, Yikun Wang, Bikui Zhang, Hualin Cai.

  As a hydrolysis mediated drug in vivo, the pharmacokinetics of melphalan are highly variable in patients. Few methodologies could simultaneously measure the concentrations of melphalan and its hydrolyzed metabolites in plasma. The aim of this study was to develop a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of melphalan and its hydrolyzed metabolites, monohydroxy melphalan (MOH melphalan) and dihydroxy melphalan (DOH melphalan). A simple protein precipitation was employed for sample preparation and melphalan-d8 was used as internal standard. Baseline separation of target analytes was achieved using an XSelect HSS T3 column (2.1 × 50 mm, 5 µm) with a gradient elution at a flow rate of 0.5 mL/min in 5 min. The monitored transitions were m/z 305.1 → 287.7 for melphalan, m/z 287.1 → 228.0 for MOH melphalan, m/z 269.3 → 251.8 for DOH melphalan, and m/z 313.1 → 295.7 for melphalan-d8. The method was fully validated in accordance with the FDA guideline. The calibration curves were established over the range of 5.22-5220 ng/mL for melphalan, 7.94-1588 ng/mL for MOH-melphalan, and 15.0-3000 ng/mL for DOH-melphalan with the regression coefficients greater than 0.99. The intra- and inter-day coefficients of variation for the analytes were ≤11.0% and all the biases were less than 8.3%. The method has been successfully applied to the quantification of melphalan and its metabolites in clinical plasma samples obtained from hematopoietic stem cell transplantation patients who received a dose of melphalan for pre-transplant conditioning.

Keywords:  Determination; Human plasma; Hydrolysis; LC-MS/MS; Melphalan; Metabolites

DOI:  https://doi.org/10.1016/j.jchromb.2023.123698
Saudi Pharm J. 2023 Apr;31(4): 547-553

Determination of Ruboxistaurin analysis in rat plasma utilizing LC-MS/MS technique.

Bushra T AlQuadeib, Fadilah S Aleanizy, Fulwah Y Alqahtani, Rehab A Alshammari, Amal Aldarwesh, Ibrahim Alsarra.

   Background: Ruboxistaurin (RBX) used to treat retinopathy in diabetic patients which caused by microvascular damage and leakage which contributes to visual loss. There are no published studies on the use of liquid chromatography-tandem mass spectrometry for development and validation of a simple, sensitive, and accurate method for measuring RBX in rat plasma.
Method: Chromatographic separation of RBX was achieved using ultra-performance liquid chromatography. Multiple-reaction monitoring quantification used RBX [M + H] + ion at m/z 469.18 and daughter ions at m/z 84, 58.12, and 98.10. Atorvastatin was used as internal standard (IS), has a single daughter ion, and was identified using m/z 559.6 → 249.9. Validation of the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for RBX in rat plasma for linearity (greater than0.997) was carried out at 25-1000 ng/mL.
Results: In rat plasma, the accuracy was within 3.4%, and the intra- and inter-day precision was within 11.8%. Stability, recovery, and matrix effect were all within acceptable limits. The drug retention time (0.85 ± 0.03 min) was remarkably short.
Conclusion: The method developed in the current study is suitable to quantify RBX in plasma or bulk doses.

Keywords:  LC-MS/MS; Plasma; Rat; Ruboxistaurin; Validation

DOI:  https://doi.org/10.1016/j.jsps.2023.02.007
Bioanalysis. 2023 Apr 21.

Simultaneous determination of four antibiotics in human plasma by high-performance LC-MS/MS: application to therapeutic drug monitoring.

Hongchuan Liu, Xiaojia Yu, Ting Hu, Feifei Han, Zhuoling An, Rui Zhao.

  Background: Aimed to simultaneously measure linezolid, voriconazole, cefoperazone and fluconazole in human plasma suitable for therapeutic drug monitoring applications, a robust, rapid and easy-to-use HPLC-MS/MS approach was developed and validated. Materials & methods: Protein precipitation was used to prepare analytes from 100 μl plasma. HPLC was employed for analyte separation, and quantification was conducted via multiple reaction monitoring in positive ion mode. The methodology was fully validated. Results & conclusion: All four antibiotics were found to be stable under the tested conditions, and accuracy values ranged from 90.96 to 113.25% and CV values were <14.0%. This HPLC-MS/MS method can be used for routine clinical therapeutic drug monitoring of linezolid, voriconazole, cefoperazone and fluconazole simultaneously.

Keywords:  HPLC–MS/MS; antibiotics; human plasma analysis; method validation; therapeutic drug monitoring

DOI:  https://doi.org/10.4155/bio-2023-0020
Wei Sheng Yan Jiu. 2023 Mar;52(2): 286-291

[Determination of amantadine, rimantadine and dimethylamantadine residues in poultry by ultra-performance liquid chromatography-tandem mass spectrometry].

Jian Ma, Yanhong Chen, Ming Zhang, Yuankun Zhao.

   OBJECTIVE: To establish a method for determination of amantadine, rimantadine and dimethylamantadine residues in poultry matrix by ultra-performance liquid chromatography-tandem mass spectrometry.
METHODS: Poultry samples were extracted with acid acetonitrile, salting out, and then the organic phase was cleaned up by C_(18) and PSA. A Waters ACQUITYTM UPLC HSS T3 column(100 mm×2.1 mm, 1.7 mm)was used for liquid chromatography separation, ESI positive ion scan was used with multiple reaction monitoring(MRM) mode and quantified by matrix-matched external standard method.
RESULTS: At the spiked level of 0.5, 1.0 and 5.0 μg/kg, the recoveries of each compound were in the range of 81.3%-91.1% with the relative standard deviations of 6.5%-11.3%. The qualitative limits of detections were 0.06-0.2 μg/kg and the quantitative limits were 0.2-0.5 μg/kg for the 3 target compounds. The established method was applied to the detection of the 3 target compounds in 30 poultry samples, and none of the target compounds exceeded the residue limits.
CONCLUSION: The method is simple, rapid, high sensitivity and good stability, with a wide variety and a certain development. It can be used for the daily monitoring of the veterinary drug residues in poultry.

Keywords:  QuEChERS; amantadine; poultry; rimantadine and dimethylamantadine; ultra-high performance liquid chromatography-tandem mass spectrometry; veterinary drug residues

DOI:  https://doi.org/10.19813/j.cnki.weishengyanjiu.2023.02.018
J Am Soc Mass Spectrom. 2023 Apr 21.

Gaussian Mixture Modeling Extensions for Improved False Discovery Rate Estimation in GC-MS Metabolomics.

Javier E Flores, Lisa M Bramer, David J Degnan, Vanessa L Paurus, Yuri E Corilo, Chaevien S Clendinen.

  The ability to reliably identify small molecules (e.g., metabolites) is key toward driving scientific advancement in metabolomics. Gas chromatography-mass spectrometry (GC-MS) is an analytic method that may be applied to facilitate this process. The typical GC-MS identification workflow involves quantifying the similarity of an observed sample spectrum and other features (e.g., retention index) to that of several references, noting the compound of the best-matching reference spectrum as the identified metabolite. While a deluge of similarity metrics exist, none quantify the error rate of generated identifications, thereby presenting an unknown risk of false identification or discovery. To quantify this unknown risk, we propose a model-based framework for estimating the false discovery rate (FDR) among a set of identifications. Extending a traditional mixture modeling framework, our method incorporates both similarity score and experimental information in estimating the FDR. We apply these models to identification lists derived from across 548 samples of varying complexity and sample type (e.g., fungal species, standard mixtures, etc.), comparing their performance to that of the traditional Gaussian mixture model (GMM). Through simulation, we additionally assess the impact of reference library size on the accuracy of FDR estimates. In comparing the best performing model extensions to the GMM, our results indicate relative decreases in median absolute estimation error (MAE) ranging from 12% to 70%, based on comparisons of the median MAEs across all hit-lists. Results indicate that these relative performance improvements generally hold despite library size; however FDR estimation error typically worsens as the set of reference compounds diminishes.

Keywords:  false positive rate; metabolite identification; spectral similarity score

DOI:  https://doi.org/10.1021/jasms.3c00039
J Pharm Biomed Anal. 2023 Mar 31. pii: S0731-7085(23)00151-6. [Epub ahead of print]230 115382

Determination of olverembatinib in human plasma and cerebrospinal fluid by an LC-MS/MS method: Validation and clinical application.

Dong Xiang, Tinghui Zhao, Jue Wang, Yang Cao, Qiuxia Yu, Lu Liu, Hengyi Yu, Xiping Li, Ninghong Li, Yang Yi, Xuepeng Gong.

  A sensitive and robust LC-MS/MS method has been developed and validated for olverembatinib quantification in human plasma and cerebrospinal fluid (CSF). The method involved liquid-liquid extraction with methyl tertiary butyl ether for plasma pretreatment and precipitation enrichment with methanol for CSF pretreatment. Separation was achieved on the C18 column with gradient elutions of 10 mM ammonium formate in water and methanol-acetonitrile (50:50,v/v). Analyte detection was conducted by electrospray ionization (ESI) in a positive ion mode using multiple reaction monitoring (MRM). The m/z transitions were 533.4→433.2 for olverembatinib and m/z 502.4→394.2 for the internal standard (IS, Imatinib-d8). Calibration curves ranged from 0.500 to 50.0 ng/mL for plasma and from 0.0100 to 1.00 ng/mL for CSF. The intra- and inter-day precision and accuracy were < 15% for both plasma and CSF with four different quality control concentrations. The relative matrix effect was < 10% in plasma and artificial CSF. This method was successfully utilized for the measurement of olverembatinib concentrations in plasma and CSF from chronic myeloid leukemia patients.

Keywords:  Cerebrospinal fluid; LC-MS/MS; Olverembatinib; Plasma

DOI:  https://doi.org/10.1016/j.jpba.2023.115382
Annu Rev Biomed Eng. 2023 Apr 17.

Analytical Techniques for Single-Cell Biochemical Assays of Lipids.

Ming Yao, Manibarathi Vaithiyanathan, Nancy L Allbritton.

Lipids are essential cellular components forming membranes, serving as energy reserves, and acting as chemical messengers. Dysfunction in lipid metabolism and signaling is associated with a wide range of diseases including cancer and autoimmunity. Heterogeneity in cell behavior including lipid signaling is increasingly recognized as a driver of disease and drug resistance. This diversity in cellular responses as well as the roles of lipids in health and disease drive the need to quantify lipids within single cells. Single-cell lipid assays are challenging due to the small size of cells (∼1 pL) and the large numbers of lipid species present at concentrations spanning orders of magnitude. A growing number of methodologies enable assay of large numbers of lipid analytes, perform high-resolution spatial measurements, or permit highly sensitive lipid assays in single cells. Covered in this review are mass spectrometry, Raman imaging, and fluorescence-based assays including microscopy and microseparations. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 25 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

DOI: https://doi.org/10.1146/annurev-bioeng-110220-034007
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Apr 07. pii: S1570-0232(23)00119-8. [Epub ahead of print]1222 123709

Expeditious quantification of plasma tacrolimus with liquid chromatography tandem mass spectrometry in solid organ transplantation.

Tanja R Zijp, Tim J Knobbe, Kai van Hateren, Jan Roggeveld, Hans Blokzijl, C Tji Gan, Stephan Jl Bakker, Erwin M Jongedijk, TransplantLines Investigators, Daan J Touw.

  Traditionally, tacrolimus is assessed in whole blood samples, but this is suboptimal from the perspective that erythrocyte-bound tacrolimus is not a good representative of the active fraction. In this work, a straightforward and rapid method was developed for determination of plasma tacrolimus in solid organ transplant recipients, using liquid chromatography tandem mass spectrometry (LC-MS/MS) with heated electrospray ionisation. Sample preparation was performed through protein precipitation of 200 µl plasma with 500 µl stable isotopically labelled tacrolimus I.S. in methanol, where 20 µl was injected on the LC-MS/MS system. Separation was done using a chromatographic gradient on a C18 column (50 × 2.1 mm, 2.6 µm). The method was linear in the concentration range 0.05-5.00 µg/L, with within-run and between-run precision in the range 2-6 % and a run time of 1.5 min. Furthermore, the method was validated for selectivity, sensitivity, carry-over, accuracy and precision, process efficiency, recovery, matrix effect, and stability following EMA and FDA guidelines. Clinical validation was performed in 2333 samples from 1325 solid organ transplant recipients using tacrolimus (liver n = 312, kidney n = 1714, and lung n = 307), which had median plasma tacrolimus trough concentrations of 0.10 µg/L, 0.15 µg/L and 0.23 µg/L, respectively. This method is suitable for measurement of tacrolimus in plasma and will facilitate ongoing observational and prospective studies on the relationship of plasma tacrolimus concentrations with clinical outcomes.

Keywords:  Alternative matrices; Bioanalysis; LC-MS/MS; Tacrolimus; Transplant

DOI:  https://doi.org/10.1016/j.jchromb.2023.123709
Wei Sheng Yan Jiu. 2023 Mar;52(2): 280-291

[Determination of three furfural compounds in coffee and coffee products by gas chromatography-tandem mass spectrometry with internal standard isotope].

Jianguo Wang, Yue Wang, Fang Wang, Hong Chang, Kai Lei, Guofeng Zhang, Yanchun Wang.

   OBJECTIVE: To establish a method for the determination of three furfural compounds in coffee and its products by gas chromatography-tandem mass spectrometry.
METHODS: The samples were extracted with ethanol water(1∶2, V∶V) solution, ultrasonic with 10% Na_2CO_3 solution for 5 min, purified with 100 mg C_(18), 50 mg Srong Cation exchang(SCX), 150 mg anhydrous MgSO_4, separated by HP-INNOWAX capillary column(30 m×0.25 mm, 0.25 μm), detected by gas chromatography-tandem mass spectrometry, and quantified by isotope internal standard method.
RESULTS: The correlation coefficients(r) of the three furfural compounds were all greater than 0.999, the limits of detection were 0.004-0.011 mg/kg, and the limits of quantitation were 0.013-0.031 mg/kg. The average recoveries were 86.0%-112% and the relative standard deviations were 4.1%-10.6%(n=6), at 3 supplemental levels in 3 different coffee substrates. Nine samples of coffee beans, instant coffee and coffee drinks were tested, and all three components to be tested were detected.
CONCLUSION: The method is simple, rapid, sensitive, with good accuracy and precision. It is suitable for the determination of three furfural compounds in coffee and its products.

Keywords:  coffee; furfural compounds; gas chromatography-tandem mass spectrometry

DOI:  https://doi.org/10.19813/j.cnki.weishengyanjiu.2023.02.017
RSC Adv. 2023 Apr 11. 13(17): 11642-11651

A novel smartphone HPTLC assaying platform versus traditional densitometric method for simultaneous quantification of alfuzosin and solifenacin in their dosage forms as well as monitoring content uniformity and drug residues on the manufacturing equipment.

Mina Wadie, Ezzat M Abdel-Moety, Mamdouh R Rezk, Hoda M Marzouk.

The large popularity and rapid technology of smartphones have opened new avenues for their integration into different analytical methodologies and drug quality monitoring as a portable, easily accessible, and user-friendly detector. Herein, a novel and portable smartphone-based high-performance thin layer chromatographic (HPTLC) approach is proposed for the simultaneous analysis of two urological drugs, alfuzosin and solifenacin, which treat benign prostatic hyperplasia accompanied by overactive bladder syndrome. First, chromatographic separation was accomplished using an ecofriendly mobile phase, then the developed plates were visualized using Dragendorff's reagent and photographed via a smartphone's rear-facing camera fixed on a fabricated two-illumination-source chamber. The intensities of the drug spots were quantified using open-source image analysis software ImageJ over the concentration ranges of 2.0 to 30.0 μg per band for both drugs with acceptable results in ICH validation parameters. To improve the method's accuracy and reproducibility, various construction and shooting key parameters were investigated and optimized. Moreover, the study was extended to compare the obtained results with those of a benchtop densitometric method using a Camag TLC Scanner 3 at 215.0 nm; the densitometric method provided an additional assessment tool for peak purity and was capable of assaying lower drug concentrations over a linearity range of 0.2-8.0 μg per band for alfuzosin and 0.1-6.0 μg per band for solifenacin. The fast, simple, reliable, green merits of the proposed HPTLC/smartphone method suggest that it is an excellent platform for assaying marketed combined capsules and assuring their content uniformity. Moreover, the high sensitivity of the densitometric method was used, for the first time, to determine the residual content of the cited drugs on manufacturing equipment surfaces for cleaning validation. Finally, the environmental impact of the developed methods was evaluated based on green analytical chemistry principles.

DOI: https://doi.org/10.1039/d3ra01211e
Bioanalysis. 2023 Apr 19.

LC-MS/MS method for the quantitation of OCT1 biomarker isobutyrylcarnitine in human plasma with clinical sample analysis.

Amy Troop, Eugene Kadar, Emi Kimoto, A David Rodrigues, Christopher Holliman.

  Aim: Isobutyrylcarnitine (IBC) is a possible biomarker for hepatic OCT1, as IBC plasma concentrations are reduced when OCT1 is inhibited. An accessible, characterized assay is needed to quantitate IBC in human plasma. Materials & methods: A triple quadrupole MS surrogate matrix assay for the quantitation of IBC was characterized to support a first-in-human study. Results: An assay for IBC quantitation was fully characterized for accuracy, precision, selectivity and parallelism. IBC was measured in a clinical study and the data were correlated to the in vitro model prediction. Conclusion: A triple quadrupole-based assay for IBC should broaden the monitoring of IBC for OCT1 inhibition in early clinical trials, generating the data needed to establish IBC as a valid biomarker.

Keywords:  OCT1 transporter; biomarkers; characterization; drug–drug interaction; isobutyrylcarnitine

DOI:  https://doi.org/10.4155/bio-2022-0228
J AOAC Int. 2023 Apr 20. pii: qsad048. [Epub ahead of print]

Analysis of 10 phthalate esters in water-based adhesives by supercritical fluid chromatography-tandem mass spectrometry combined with spherical carbons-based dispersion solid-phase extraction.

Jun Yan, Zhiyan Chen, Chunqiong Wang, Yun Xue, Li Lin, Chen He, Xiao Zhou, Fei Yang, Yun Zhou, Gangling Tang.

BACKGROUND: Spherical carbons have porous structure and large surface area for adsorption of macromolecules in water-based adhesives. SFC can improve selectivity and obtain better separation for phthalate esters.
OBJECTIVE: The aim of this study was to develop a simple and green method for the simultaneous determination of 10 phthalate esters in water-based adhesive using supercritical fluid chromatography-tandem mass spectrometry with dispersion solid-phase extraction by spherical-carbons.
METHOD: Separation of phthalate esters on a Viridis HSS C18 SB column and the parameters affecting the extraction were evaluated.
RESULTS: Good accuracy and precision were obtained with the recoveries at 0.5, 2.0, and 10.0 mg/kg ranging from 82.9% to 99.5% and the intra- and inter-day precision less than 7.0%. The method had excellent sensitivity with limits of detection in the range of 0.015-0.029 mg/kg. In the 10-500 ng/mL concentration range, the linear correlation coefficients of all compounds were between 0.9975 and 0.9995.
CONCLUSIONS: The method was applied to the determination of 10 phthalate esters in actual samples. This method is simple and rapid with low solvent consumption and high extraction efficiency. When applied to the determination of phthalate esters in actual samples, the method is sensitive and accurate and can meet the batch processing requirements for trace phthalate esters in water-based adhesives.
HIGHLIGHTS: Phthalate esters in water-based adhesives can be determined using inexpensive materials and simple procedures with supercritical fluid chromatography.

DOI: https://doi.org/10.1093/jaoacint/qsad048
Ther Drug Monit. 2023 Apr 14.

Simultaneous Determination of Rifamycin Antibiotics and Their Active Metabolites in Human Plasma Using UHPLC-MS/MS to Evaluate Their Impact on Target Peak Concentrations: A Short Communication.

Ling-Jie Wu, Zhen-Jie Ye, Xiao-Ying Zhang, Xiao-Long Zhang, Ai-Xian Zheng, Xiao-Long Liu, Xiao-Ling Yu.

BACKGROUND: Standard and proper antituberculosis (anti-TB) treatment is essential for patients with TB, and rifamycin antibiotics are key components of anti-TB therapy. Therapeutic drug monitoring (TDM) of rifamycin antibiotics can shorten the time to response and complete treatment of TB. Notably, antimicrobial activities of the major active metabolites of rifamycin are similar to those of their parent compounds. Thus, a rapid and simple assay was developed for simultaneous determination of rifamycin antibiotics and their major active metabolites in plasma to evaluate their impact on target peak concentrations. Here, the authors have developed and validated a method for simultaneous determination of rifamycin antibiotics and their active metabolites in human plasma using ultrahigh-performance liquid chromatography tandem mass spectrometry.
METHODS: Analytical validation of the assay was performed in accordance with the bioanalytical method validation guidance for industry described by the US Food and Drug Administration and the guidelines for bioanalytical method validation described by the European Medicines Agency.
RESULTS: The drug concentration quantification method for rifamycin antibiotics, including rifampicin, rifabutin, and rifapentine, and their major active metabolites was validated. Significant differences in the proportions of active metabolites in rifamycin antibiotics may affect the redefinition of their effective concentration ranges in the plasma. The method developed herein is expected to redefine the ranges of "true" effective concentrations of rifamycin antibiotics (including parent compounds and their active metabolites).
CONCLUSIONS: The validated method can be successfully applied for high-throughput analysis of rifamycin antibiotics and their active metabolites for TDM in patients receiving anti-TB treatment regimens containing these antibiotics. Proportions of active metabolites in rifamycin antibiotics markedly varied among individuals. Depending on the clinical indications of patients, the therapeutic ranges for rifamycin antibiotics may be redefined.

DOI: https://doi.org/10.1097/FTD.0000000000001098
Anal Chem. 2023 Apr 20.

Efficient Sample Preparation System for Multi-Omics Analysis via Single Cell Mass Spectrometry.

Peng Zhao, Yongxiang Feng, Junhan Wu, Junwen Zhu, Jinlei Yang, Xiaoxiao Ma, Zheng Ouyang, Xinrong Zhang, Wenpeng Zhang, Wenhui Wang.

Mass spectrometry (MS) has become a powerful tool for metabolome, lipidome, and proteome analyses. The efficient analysis of multi-omics in single cells, however, is still challenging in the manipulation of single cells and lack of in-fly cellular digestion and extraction approaches. Here, we present a streamlined strategy for highly efficient and automatic single-cell multi-omics analysis by MS. We developed a 10-pL-level microwell chip for housing individual single cells, whose proteins were found to be digested in 5 min, which is 144 times shorter than traditional bulk digestion. Besides, an automated picoliter extraction system was developed for sampling of metabolites, phospholipids, and proteins in tandem from the same single cell. Also, 2 min MS2 spectra were obtained from 700 pL solution of a single cell sample. In addition, 1391 proteins, phospholipids, and metabolites were detected from one single cell within 10 min. We further analyzed cells digested from cancer tissue samples, achieving up to 40% increase in cell classification accuracy using multi-omics analysis in comparison with single-omics analysis. This automated single-cell MS strategy is highly efficient in analyzing multi-omics information for investigation of cell heterogeneity and phenotyping for biomedical applications.

DOI: https://doi.org/10.1021/acs.analchem.2c05728
Nat Prod Rep. 2023 Apr 17.

Analytical methods for the analysis of volatile natural products.

Yue Li.

Covering: 2000 to 2022This article reviews the latest developments of analytical methods of volatile natural products. Volatile organic compounds (VOCs) released from biological systems correspond to a series of compounds, originating from primary and secondary metabolites. These compounds are important for intra- and interspecies chemical communication and interaction of living organisms. These valuable natural products can find applications in many fields, including foods, human nutrition, pharmaceuticals, perfumes, cosmetics and so on. Therefore, the deciphering of their structures is of increasing importance in many fields of natural product chemistry. Due to the large diversity of these compounds, there is no "single" analytical instrument or method that can be used to study all of them. Furthermore, most of the volatile compounds can be collected only in low concentrations. Therefore, their detection, identification and structural characterization are challenging tasks. The review briefly describes the extraction and preparation methods of samples, then introduces the tools of instrumental analysis utilized to identify or quantify the VOCs of natural products, including spectroscopic and mass spectrometric methods, such as offline GC-MS, multi-dimensional GC-MS, and online approaches including PTR-MS, SIFT-MS, SEMI-MS, DART-MS etc. The current challenges of analytical techniques and future directions are also briefly discussed.

DOI: https://doi.org/10.1039/d2np00079b
Anal Bioanal Chem. 2023 Apr 21.

XAI-enabled neural network analysis of metabolite spatial distributions.

Wenwu Ma, Lanfang Luo, Kun Liang, Taoyan Liu, Jiali Su, Yuefan Wang, Jun Li, S Kevin Zhou, Ng Shyh-Chang.

  We used deep neural networks to process the mass spectrometry imaging (MSI) data of mouse muscle (young vs aged) and human cancer (tumor vs normal adjacent) tissues, with the aim of using explainable artificial intelligence (XAI) methods to rapidly identify biomarkers that can distinguish different classes of tissues, from several thousands of metabolite features. We also modified classic neural network architectures to construct a deep convolutional neural network that is more suitable for processing high-dimensional MSI data directly, instead of using dimension reduction techniques, and compared it to seven other machine learning analysis methods' performance in classification accuracy. After ascertaining the superiority of Channel-ResNet10, we used a novel channel selection-based XAI method to identify the key metabolite features that were responsible for its learning accuracy. These key metabolite biomarkers were then processed using MetaboAnalyst for pathway enrichment mapping. We found that Channel-ResNet10 was superior to seven other machine learning methods for MSI analysis, reaching > 98% accuracy in muscle aging and colorectal cancer datasets. We also used a novel channel selection-based XAI method to find that in young and aged muscle tissues, the differentially distributed metabolite biomarkers were especially enriched in the propanoate metabolism pathway, suggesting it as a novel target pathway for anti-aging therapy.

Keywords:  Aging; Deep neural networks; Feature extraction; Mass spectrometry imaging; Pathway analysis

DOI:  https://doi.org/10.1007/s00216-023-04694-8
ACS Omega. 2023 Apr 11. 8(14): 12968-12979

Rapid and Direct Assessment of Asphalt Volatile Organic Compound Emission Based on Carbon Fiber Ionization Mass Spectrometry.

Shanshan Wang, Chenchen Yang, Junteng Zhao, Chenyao Li, Xinhao Fan.

Due to the complicacy of asphalt fumes, the analytical methods for investigating volatile organic compounds (VOCs) are very limited. In this study, a direct and real-time analysis method based on carbon fiber ionization mass spectrometry (CFI-MS), an ambient mass spectrometric technique, was established and successfully applied in the analysis of asphalt VOCs. The asphalt VOCs can be directly detected in the open atmosphere without the collection step of asphalt fumes, and the mass spectra of one asphalt sample can be obtained in a few seconds in both positive and negative ion modes. By investigating the mass spectral changes of asphalt fumes at different heating temperatures ranging from 50 to 200 °C, the temperature factor of asphalt fume emission was demonstrated in this work. The research results demonstrate that the complexity of asphalt fumes is positively related to the applied temperature. Moreover, the VOCs of saturates, aromatics, resins, and asphaltenes fractions were also analyzed by the direct analysis method. The result shows that aromatics contribute most to the emission of VOCs. In addition, the obtained mass spectra combined with the principal component analysis method show the great potential to quickly screen VOC inhibitors of asphalt materials.

DOI: https://doi.org/10.1021/acsomega.3c00163
J Chromatogr A. 2023 Apr 17. pii: S0021-9673(23)00215-7. [Epub ahead of print]1697 463989

What about nitrogen? Using nitrogen as a carrier gas during the analysis of petroleum biomarkers by gas chromatography mass spectrometry.

Colin W Taylor, Stephen A Bowden.

  Gas chromatography mass spectrometry (GC-MS) is a commonly used method for organic geochemistry for both academic research and applications such as petroleum analysis. Gas chromatography requires a carrier gas, which needs to be both volatile and stable and in most organic geochemical applications helium or hydrogen have been used, with helium predominating for gas chromatography mass spectrometry. Helium, however, is becoming an increasingly scarce resource and is not sustainable. Hydrogen is the most commonly considered alternative carrier gas to helium but has characteristics that in certain respects make its use less practical, foremost is that hydrogen is flammable and explosive. But as hydrogen is increasingly used as a fuel, higher demand may also make its use less desirable. Here we show that nitrogen can be used for the GC-MS analysis of fossil lipid biomarkers. Using nitrogen, chromatographic separation of isomers and homologues can be achieved, but sensitivity is orders of magnitude less than for helium. It is reasonable to use nitrogen as a carrier gas in applications where low levels of detection are not needed, such as the characterization of samples of crude oil or foodstuffs, or potentially as part of a gas-mixture seeking to reduce helium-demand but maintain a level of chromatographic separation sufficient to support proxy-based characterizations of petroleum.

Keywords:  Carrier gas; Gas chromatography mass spectrometry (GC-MS); Organic geochemistry; Petroleum biomarker; Sustainability

DOI:  https://doi.org/10.1016/j.chroma.2023.463989
Methods Mol Biol. 2023 ;2662 219-239

Isolation and Mass Spectrometry-Based Profiling of Major Lipids in Brown Adipose Tissue.

Dongliang Lu, Hideji Fujiwara, Irfan J Lodhi, Fong-Fu Hsu.

  Brown adipose tissue (BAT) is an important regulator of metabolic homeostasis through its role in adaptive thermogenesis and control of whole-body glucose metabolism. Lipids play multiple roles in BAT functions, including serving as a fuel source for thermogenesis, mediating inter-organelle cross talk, and acting as BAT-derived signaling molecules that influence systemic energy metabolism. Profiling of various lipids in BAT under distinct metabolic states could provide new insights into their roles in the biology of the thermogenic fat. In this chapter, we describe a step-by-step workflow starting from sample preparations to mass spectrometry-based analysis of fatty acids and phospholipids in BAT.

Keywords:  Brown adipose tissue; Folch method; Free fatty acid; Mass spectrometry; Phospholipid; Solid phase extraction; Sphingolipid

DOI:  https://doi.org/10.1007/978-1-0716-3167-6_20
J AOAC Int. 2023 Apr 18. pii: qsad046. [Epub ahead of print]

An Antiviral Drug-Peramivir: Degradation and Identification of Impurities and the Endorsement of HPLC-MS Method.

Thulaseedhar Alumuri, Karuna Sree Merugu, Namburi L A Amarababu, Aravind Kurnool, Arunachalam SaravanaVadivu, Selvakumar Balasubramanian.

BACKGROUND: Peramivir, a neuraminidase inhibitor that serves as a transition-state analogue for influenza, inhibiting the formation of new viruses in infected cells and also been approved for intravenous administration.
OBJECTIVE: To validate the HPLC method to identify the degraded products of the antiviral drug Peramivir.
METHODS: Herein, we report the identification of degraded compounds formed after the degradation of the Peramvir an antiviral drug done by the acid, alkali, peroxide, thermal and photolytic degradation. At the level of toxicology, a technique was devised for the isolation and measurement of the compound known as peramivir.
RESULTS: A sensitive and reliable liquid chromatography-tandem mass spectrometry technique to the quantitative measurement of Peramivir and also its impurities was developed and verified in order to comply with the recommendations made by ICH. The proposed protocol was in the 50-750 µg/mL range. RSD values less than 2.0% indicate good recovery in the range of 98.36%-102.57%. Within the studied range, the calibration curves demonstrated good linearity, in addition, the coefficient of fitting correlation was more than 0.999 for every impurity. Contaminant quantitative analysis revealed the high efficiency at a low level.
CONCLUSION: Given its ability to separate degradation products, quantitative analysis is used to detect and quantify known and unknown impurities and degradants in the Peramivir drug substance during routine analysis and stability studies. No significant degradation was found in peroxide and photolytic degradation studies.
HIGHLIGHTS: An HPLC method was developed and put to the test in order to analyse the behavior of the impurities of peramivir as they degraded when subjected to the stress conditions suggested by the ICH.The compound was discovered to be stable under peroxide and photo conditions but degradable towards the acid, base and thermal. The method developed was extremely precise, linear, accurate, robust, and rugged.As a result, this technology has the potential to be used in the medication production process for regular impurity analysis as well as for the stability analysis of peramivir.

DOI: https://doi.org/10.1093/jaoacint/qsad046