bims-metlip Biomed News
on Methods and protocols in metabolomics and lipidomics
Issue of 2025–04–13
39 papers selected by
Sofia Costa, Matterworks
  1. Evaluation of ion source parameters and liquid chromatography methods for plasma untargeted metabolomics using orbitrap mass spectrometer.
  2. Automated and Fully Validated High-Throughput LC-MS/MS Assay for Analyzing Multiple Drugs of Abuse in Oral Fluids Using Novel Features in Sample Preparation and Chromatographic Conditions.
  3. Acoustic ejection Mass spectrometry: the potential for personalized medicine.
  4. Multispectrum ModiFinder Site Localization Performance.
  5. Development and validation of a highly sensitive HPLC method for quantifying cardiovascular drugs in human plasma using dual detection.
  6. Development and validation of an LC-MS/MS method for quantitative determination of LXT-101 sustained-release suspension, a novel drug in treating prostate cancer, in beagle plasma.
  7. Development and validation of a fast LC-MS/MS method for the quantitation of creatine and taurine in sports supplements.
  8. Simultaneous determination of three iodinated contrast media in human plasma by LC/MS-MS and its clinical application.
  9. Instrument Multiplexing: Amplified Throughput for Measurement of Vitamin B1 in Whole Blood Using Parallel Liquid Chromatography Systems Interfaced to a Single Mass Spectrometer.
  10. Rank annihilation factor analysis for kinetic spectrophotometric determination of morphine in unknown samples.
  11. Protocol for dual metabolomics and proteomics using nanoflow liquid chromatography-tandem mass spectrometry.
  12. Liquid chromatography tandem mass spectrometry (LC-MS/MS) candidate reference measurement procedure for urine albumin.
  13. Comparison of Dip-it-DART-Orbitrap-MS With Nitrogen Plasma to HPLC/Orbitrap-MS in Profiling Aromatic Glycoconjugation in White Grapes.
  14. In-depth characterization of acylcarnitines: utilizing nitroxide radical-directed dissociation in tandem mass spectrometry.
  15. Pharmacometabolomics: An emerging platform for understanding the pathophysiological processes and therapeutic interventions.
  16. High-performance liquid chromatography-tandem mass spectrometry for simultaneous determination of 23 antidepressants and active metabolites in human serum and its application in therapeutic drug monitoring.
  17. A rapid and sensitive LC-MS/MS method for the simultaneous determination of chlorfenapyr and its major metabolite tralopyril in human plasma: From method development, validation to clinical application.
  18. Determination by UHPLC-QTOF-HRMS of Phosphatidylethanol (PEth) in Dried Blood Spots: Method Validation and Practical Application of a Rising Alcohol Abuse Biomarker With Minimally Invasive Sampling.
  19. MSIght: A Modular Platform for Improved Confidence in Global, Untargeted Mass Spectrometry Imaging Annotation.
  20. Towards Generalizable In Silico Predictions of Differential Ion Mobility Using Machine Learning and Customized Fingerprint Engineering.
  21. Preparation of multicellular spheroid sections embedded with sodium carboxymethyl cellulose for mass spectrometry imaging.
  22. Optimization of Parallel Artificial Liquid Membrane Extraction for the Determination of Over 50 Psychoactive Substances in Oral Fluid Through UHPLC-MS/MS.
  23. Simultaneous quantification of methotrexate, 7-hydroxymethotrexate and creatinine in serum by LC-MS/MS for predicting delayed elimination.
  24. Internal Standard Utilization Strategies for Quantitative Paper Spray Mass Spectrometry.
  25. Building a Bridge Between Ambient MS and LC-MS by Non-Exhaustive Microdesorption.
  26. Spatial Glycomics and Kidney Disease.
  27. Integrating Ambient Ionization Mass Spectrometry Imaging and Spatial Transcriptomics on the Same Cancer Tissues to Identify Gene-Metabolite Correlations.
  28. RapidMass: A Graphical Data Processing Application for Automated Species Authentication in High-Throughput Mass Spectrometry.
  29. An ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of deoxycholic acid and application to a pharmacokinetic study in human plasma.
  30. Comprehensive and Explainable Fragmentation: A Machine Learning Approach for Fast and Accurate Mass Spectrum Prediction.
  31. Innovation in venlafaxine detection: Development and application of electroanalytical method using a boron-doped diamond electrode and performance comparison with UHPLC-MS/MS.
  32. Regulated bioanalysis of antibody-drug conjugates using LC-MS.
  33. An ultra-high-performance tandem mass spectrometry method to quantify tryptophan metabolites in aqueous humor of primary angle-closure glaucoma patients.
  34. Distinguishing the Metabolic Effect of Fetal and Adult Fibrinogen on Human Fibroblast Cell Culture by IR-MALDESI Mass Spectrometry Imaging.
  35. Electrophoresis-enhanced paper spray mass spectrometry.
  36. Metabolomic Profiling of Three Body Fluids Differentiates UWS and MCS in Disorders of Consciousness.
  37. Harmonization of FT-ICR-MS Instruments for Interoperable Multi-Laboratory Comprehensive Compositional Profiling.
  38. Lipidomics and temporal-spatial distribution of organelle lipid.
  39. Development of High-Throughput Quantitative Imaging Mass Spectrometry for Analysis of Drug Distribution in Tissues.
  1. J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Mar 19. pii: S1570-0232(25)00116-3. [Epub ahead of print]1257 124564
    Evaluation of ion source parameters and liquid chromatography methods for plasma untargeted metabolomics using orbitrap mass spectrometer.
    Hailemariam Abrha Assress, Ahsan Hameed, Lindsay M Pack, Mario G Ferruzzi, Renny S Lan.
      Although untargeted metabolomics holds promise for study of metabolites in human health and disease, robust method development and optimization are needed to reduce potential analytical biases and to ensure comprehensive, high-throughput results. In this study, the effect of mass spectrometer (MS) ion source parameters on the signal reproducibility and number of metabolite annotations during untargeted metabolomics is shown. Furthermore, different mobile phase gradients and columns (five reversed phase (RP)-C18 and two hydrophilic interaction liquid chromatography (HILIC) columns) were evaluated for untargeted metabolomics of blood plasma extracts. Positioning the electrospray needle at the farthest on the Z-direction and the closest tested position on the Y-direction with respect to the mass spectrometry inlet produced the best signal reproducibility and the greatest number of metabolite annotations. Moreover, optimal ion source conditions included a positive spray voltage between 2.5 and 3.5 kV, a negative spray voltage between 2.5 and 3.0 kV, vaporization and ion transfer tube (ITT) temperature between 250 and 350 °C, 30 to 50 arbitrary units of sheath gas, and at least 10 auxiliary gas units. Despite the differences in chromatographic characteristics, the different RP columns assessed showed comparable performance in terms of number of metabolites annotated. For HILIC columns, a zwitterionic column demonstrated better performance than an amide column. Finally, as compared with use of a RP column alone, use of both the optimal RP and HILIC approaches expanded metabolome coverage: the number of metabolites annotated increased by 60 %. This study highlights the significance of fine-tuning the MS ion source parameters and optimizing chromatographic conditions on metabolome coverage during untargeted metabolomics of plasma samples.
    Keywords:  ESI needle position; ESI parameters; HILIC columns; Liquid chromatography gradient; Reversed phase columns; Untargeted metabolomics
    DOI:  https://doi.org/10.1016/j.jchromb.2025.124564
  2. J Mass Spectrom. 2025 May;60(5): e5132
    Automated and Fully Validated High-Throughput LC-MS/MS Assay for Analyzing Multiple Drugs of Abuse in Oral Fluids Using Novel Features in Sample Preparation and Chromatographic Conditions.
    Joakim Tan, Alexia Rylski, Anders Bergqvist, Niclas Nikolai Stephanson.
      Oral fluid sampling offers advantages over other biological matrices, mainly due to its noninvasive procedure avoiding privacy intrusion. The fully automated sample preparation procedure is based on salting-out assisted liquid-liquid extraction (SALLE) combined with high-efficiency LC-MS/MS methods for both screening and confirmation of 37 drugs and incorporates novel features enabling direct injection of acetonitrile extracts into an innovative chromatographic system. The methods' drug panel includes opioids, benzodiazepines, benzodiazepine-like drugs, cannabinoids, and stimulants. A full method validation was performed using OF/buffer from Greiner Bio-ONE International and Quantisal saliva collection devices. The validation included assessments of linearity, sensitivity, precision, accuracy, extraction recovery, matrix effects, process efficiency, stability, and carryover. All compounds demonstrated linearity across the concentration range 1-25 ng/mL, with R2 ≥ 0.99. Both methods' limit of detection ranged between 0.001 and 0.03 ng/mL, and the limit of quantification ranged between 0.02 and 0.09 ng/mL. Precision was ≤ 14.8% for screening and ≤ 8.5% for the confirmation method. Accuracy was ± 13.6% for screening and ± 8.7% (except at 0.5 and 1 ng/mL, where it was ± 25.3% and ± 17.6%, respectively) for the confirmation method. Extraction recoveries ranged from 40.0% to 95.1%, except for hydromorphone (27.4%) and morphine (34.4%). Although matrix effects were observed for a large number of compounds to varying degrees, they were largely compensated for by the use of deuterium- and 13C-labeled internal standards (IS). IS-corrected overall process efficiency ranged from 100.7% to 119.1% with precision (CV%) ≤ 10.8% for all compounds. Spiked calibrators and QC samples in OF were stable in autosampler for up to 72 h and in the freezer for 3 days. Methanol working solutions were stable for 6 months. No significant carryover was observed. The methods have been successfully implemented in the routine analysis of approximately > 1000 samples per month since March 2024.
    Keywords:  Greiner Bio‐One; LC‐MS/MS; Quantisal; SALLE; drugs of abuse; liquid chromatography tandem mass spectrometry; oral fluid; saliva; salting‐out assisted liquid–liquid extraction
    DOI:  https://doi.org/10.1002/jms.5132
  3. Expert Rev Proteomics. 2025 Apr 09.
    Acoustic ejection Mass spectrometry: the potential for personalized medicine.
    Chang Liu.
       INTRODUCTION: The emergence of personalized medicine (PM) has shifted the focus of healthcare from the traditional 'one-size-fits-all' approach to strategies tailored to individual patients, accounting for genetic, environmental, and lifestyle factors. Acoustic ejection mass spectrometry (AEMS) is a novel technology that offers a robust and scalable platform for high-throughput MS readout. AEMS achieves analytical speeds of one sample per second while maintaining high data quality, broad compound coverage, and minimal sample preparation, making it an invaluable tool for PM.Areas covered: This article explores the potential of AEMS in critical PM applications, including therapeutic drug monitoring (TDM), proteomics, metabolomics, and mass spectrometry imaging. AEMS simplifies conventional workflows by minimizing sample preparation, enhancing automation compatibility, and enabling direct analysis of complex biological matrices.
    EXPERT OPINION: Integrating AEMS with orthogonal separation techniques such as differential mobility spectrometry (DMS) further addresses challenges in isomer discrimination, expanding the platform's analytical capabilities. Additionally, the development of high-throughput data processing tools could further enable AEMS to accelerate the development of personalized medicine.
    Keywords:  High-throughput analysis; Metabolomics; Personalized medicine; Proteomics; acoustic ejection mass spectrometry; mass spectrometry imaging; therapeutic drug monitoring
    DOI:  https://doi.org/10.1080/14789450.2025.2491356
  4. J Am Soc Mass Spectrom. 2025 Apr 09.
    Multispectrum ModiFinder Site Localization Performance.
    Mohammad Reza Zare Shahneh, James Pyke, Emma E Rennie, Mingxun Wang.
      Tandem mass spectrometry (MS/MS) is a powerful technique for structural identification of small molecules, yet a significant portion of MS/MS spectra from untargeted experiments remain unidentifiable through spectrum library matching. ModiFinder, a computational tool, tackles this issue by predicting the site of chemical modifications on known analogs of the unidentified compounds using MS/MS data. However, ModiFinder's performance is limited by insufficient peak data and fragmentation annotation ambiguities. In this study, we investigate how incorporating MS/MS spectra from multiple collision energies and mass spectrometry adducts can enhance ModiFinder's localization accuracy. Using a data set from Agilent Technologies comprising 2150 data-rich compounds (five times larger than previously available data sets), we evaluated the impact of complementary spectral information. Our results show that combining spectra from different adducts and collision energies expands ModiFinder's localization abilities to more compounds and improves the overall performance.
    Keywords:  library search; mass spectrometry; modification site localization; structural identification
    DOI:  https://doi.org/10.1021/jasms.4c00464
  5. Sci Rep. 2025 Apr 10. 15(1): 12229
    Development and validation of a highly sensitive HPLC method for quantifying cardiovascular drugs in human plasma using dual detection.
    Khalid A M Attia, Ahmed H Abdel-Monem, Ahmed M Abdel-Raoof, Amr S Eissa.
      Cardiovascular diseases are the major cause of global mortality, and often require the concomitant use of a number of drugs to prevent and reduce these deaths. The challenge is to find effective and accurate methods for analyzing these drugs in plasma. This research introduces an innovative, sustainable HPLC-FLD method for the concurrent determination of bisoprolol (BIS), amlodipine besylate (AML), telmisartan (TEL), and atorvastatin (ATV) within human plasma. Chromatographic separation was achieved using an isocratic elution mode on a Thermo Hypersil BDS C18 column (150 × 4.6 mm, 5.0 μm), while the mobile phase comprised of ethanol and 0.03 M potassium phosphate buffer (pH 5.2) in a 40:60 ratio, with a flow rate of 0.6 mL/min. The eluate was analyzed using UV detection within the wavelength range of 210-260 nm to confirm effective separation of the four cardiovascular drugs. For enhanced specificity, a fluorescence detector was set to 227ex/298em for BIS, 294ex/365em for TEL, 274ex/378em for ATV, and 361ex/442em for amlodipine. The method was validated following the International Council for Harmonisation (ICH) guidelines. Linearity was established within the ranges of 5-100 ng/mL for BIS and AML, 0.1-5 ng/mL for TEL, and 10-200 ng/mL for ATV, ensuring accuracy and precision. The significant of the current work represented in introduction of a highly sensitive, and selective analytical method, utilizing an economical sample preparation strategy, for the simultaneous determination of four different cardiovascular drugs (bisoprolol, amlodipine, telmisartan, and atorvastatin) in spiked human plasma. The extraction of sample was carried by liquid-liquid extraction (LLE) and analyzed by LC-fluorescence detector. The chromatographic run was short (less than10 min) which is a greet economical value.
    Keywords:  Cardiovascular drugs; Fluorescence; HPLC; Human plasma; Liquid liquid extraction
    DOI:  https://doi.org/10.1038/s41598-025-94907-0
  6. Sci Rep. 2025 Apr 07. 15(1): 11868
    Development and validation of an LC-MS/MS method for quantitative determination of LXT-101 sustained-release suspension, a novel drug in treating prostate cancer, in beagle plasma.
    Jinglai Li, Lan Yin, Yuexin Li, Yutao Xue, Xiaoying Wang, Wenxia Xu, Zhenqing Zhang, Shan Xiong.
      The pharmacokinetics of LXT-101 sustained-release suspension, an anti-prostate cancer polypeptide, were studied on beagle dogs using a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Samples were prepared by the protein precipitation, evaporation and reconstitution. Chromatographic separation was performed using a Hypersil GOLD C18 column (50 mm × 2.1 mm, I.D. 5 μm). The mobile phase consisted of acetonitrile, water and formic acid (20:80:0.1, v/v/v) at a flow rate of 0.3 mL/min. The acquisition was carried out in selected reaction monitoring (SRM). The method was validated in terms of selectivity, linearity, precision and accuracy, extraction recovery and matrix effect, and stability. It showed good linearity over the range of 2-600 ng/mL (R2 = 0.9977). The intra- and inter-batch accuracy were within 93.36-93.94% and 95.61-99.27%, while the intra- and inter-batch precision were in the range of 3.23-14.26% and 5.03-11.10%, respectively. The extraction recovery and matrix effect data for LXT-101 in beagle dog plasma ranged from 75.90-126.40% and 83.13-95.50%, respectively. The stability results proved that the storage conditions, disposal, intermittent analysis and analysis techniques were valid and reliable for LXT-101 in beagle dog plasma. In the single-dose groups (20 mg/kg and 40 mg/kg), the values of AUC0-t (588.09 ± 137.79 ng/mL·d vs. 1203.62 ± 877.42 ng/mL·d) and AUC0-∞ (592.89 ± 134.21 ng/mL·d vs. 1209.97 ± 873.78 ng/mL·d) were observed increasing proportionately with the increasing dose of LXT-101 sustained-release suspension. The results in the repeated-dose group suggested the possibility of accumulation in beagle dogs.
    Keywords:  Beagle dogs; LC–MS/MS; LXT-101; Pharmacokinetics; Prostate cancer; Sustained-release suspension
    DOI:  https://doi.org/10.1038/s41598-025-96764-3
  7. Pharmazie. 2025 Mar 31. 80(1): 2-6
    Development and validation of a fast LC-MS/MS method for the quantitation of creatine and taurine in sports supplements.
    R van der Merwe, W Liebenberg, H J R Lemmer, F van der Kooy.
      Sports supplements containing a combination of creatine and taurine have seen a dramatic rise in popularity. However, adequate analytical techniques for the quantification of these metabolites in tissue samples and supplements are essential. Liquid chromatography mass spectrometry offers a selective and sensitive alternative but to date, no method has been reported for the quantification of both compounds in combination. The main objective was to develop and validate a fast analytical method using LC-MS/MS and to test its suitability on seven commercial sports supplements. An isocratic method with a run time of 2.5 min using a hydrophilic interaction liquid chromatography column and multiple reaction monitoring transitions was developed and validated for linearity, precision, LOD and LOQ, ruggedness and recovery. Spiking experiments on seven commercial samples were conducted to test for possible ion enhancement/suppression. All validation parameters fell well within acceptable limits and the spiking recoveries of the commercial samples all fell between 81-116%. The seven products revealed large discrepancies between the measured values by as much as +99.66% for creatine and as low as -83.81% for taurine as compared to the label claims. These discrepancies highlight the importance of quality control, as inaccurate labelling could lead to unintentional overdosing, which may cause gastric issues and, in severe cases, kidney problems.
    DOI:  https://doi.org/10.1691/ph.2025.4059
  8. J Pharm Biomed Anal. 2025 Apr 03. pii: S0731-7085(25)00208-0. [Epub ahead of print]262 116867
    Simultaneous determination of three iodinated contrast media in human plasma by LC/MS-MS and its clinical application.
    Shupeng Liu, Yaoyao Wang, Xiaofei Wu, Jianfang Cai, Hongyun Wang.
      Iodinated contrast media (ICM), including iohexol, iopromide and iodixanol, have significantly enhanced diagnostic accuracy, particularly in cardiovascular and cerebrovascular diseases. The three ICM is tailored to specific patient needs and diagnostic contexts. However, excessive doses of ICM may induce adverse reactions, including nephrotoxicity. Accurate measurement of ICM concentration is essential for reducing renal burden and ensuring patient safety. Current methods for quantifying ICM are often limited to single-analyte detection (especially iohexol), which is inefficient for clinical practice. Therefore, this method aims to develop and validate a rapid, generic LC-MS/MS method for simultaneously quantifying iohexol, iopromide, and iodixanol in human plasma to improve patient management and prognosis. An LC-MS/MS-based approach was established utilizing an C18 column coupled with a Xevo TQ-S triple quadrupole mass spectrometer. Sample preparation involved protein precipitation, while chromatographic separation was achieved using acetonitrile and 0.1 % formic acid in water. The developed LC-MS/MS method achieved satisfactory separation of the three ICM within 1.5 min. Calibration curves for iohexol, iopromide, and iodixanol showed good linearity in 5.00-5000, 5.00-5000 and 10.0 ∼ 10000 µg/mL, respectively. The method was effectively applied to analyze 71 plasma samples from 9 patients, highlighting its clinical utility. A rapid and generic LC-MS/MS method streamlines sample preparation and standardizes laboratory workflows, making it suitable for clinical bio-samples.
    Keywords:  Iodinated contrast media; Liquid chromatography mass spectrometry; Quantification
    DOI:  https://doi.org/10.1016/j.jpba.2025.116867
  9. Clin Chem. 2025 Apr 09. pii: hvaf029. [Epub ahead of print]
    Instrument Multiplexing: Amplified Throughput for Measurement of Vitamin B1 in Whole Blood Using Parallel Liquid Chromatography Systems Interfaced to a Single Mass Spectrometer.
    Preejith P Vachali, Erik Kish-Trier, Sophie Steckel, Elizabeth L Frank.
       BACKGROUND: Thiamine diphosphate (TDP), the active form of vitamin B1, plays an essential role in energy metabolism. TDP is analyzed in the clinical laboratory to assess the nutritional status of individuals at risk of deficiency. In recent years, demand for vitamin B1 testing has increased dramatically, prompting implementation of a high-throughput assay. We developed a method using rapid sample preparation and multiplex electrospray LC-MS/MS analysis.
    METHODS: Whole blood samples were deproteinized using trichloroacetic acid after the addition of isotope-labeled analyte (TDP-d3). TDP was separated by reversed-phase chromatography on extended pH, trifunctional silane-bonded C18 columns and analyzed using positive electrospray ionization and multiple reaction monitoring mass spectrometry. The system consisted of 4 LC instruments plumbed to a single mass spectrometer. TDP eluted in 3.15 ± 0.08 min with a run time of 9.0 min for a single stream; results for 4 streams were produced every 2.25 min. Passivation of the system was required to optimize sensitivity and peak quality.
    RESULTS: The method was linear from 20 to 1000 nmol/L. Spike-recovery experiments showed an accuracy of ±15%. The intra- and inter-day assay imprecision was ≤3%. Repeated injections of calibrators and QC materials across the four LC streams showed excellent parity (<2% imprecision). No carryover was detected. Each plate produced 81 results in 4.5 h.
    CONCLUSIONS: An accurate, specific, and high-throughput LC-MS/MS method was developed and validated to measure TDP in whole blood. Simple, fast sample preparation was employed for adaptation to a staggered injection, multiple LC-stream platform, which minimized mass spectrometer idle time significantly and improved efficiency.
    DOI:  https://doi.org/10.1093/clinchem/hvaf029
  10. Sci Rep. 2025 Apr 11. 15(1): 12523
    Rank annihilation factor analysis for kinetic spectrophotometric determination of morphine in unknown samples.
    Morteza Bahram, Somayeh Khezri, Reza Dadashi.
      The accurate and selective determination of morphine in biological and pharmaceutical samples remains a critical challenge due to matrix interferences and the need for highly sensitive detection methods. While traditional techniques such as GC-MS, HPLC-UV, and LC-MS/MS offer high sensitivity and selectivity, they often require complex sample preparation, expensive instrumentation, and extensive calibration procedures. In this study, we employ rank annihilation factor analysis (RAFA) in combination with kinetic spectrophotometry to enhance the accuracy and robustness of morphine quantification. RAFA effectively eliminates matrix interferences and resolves overlapping spectral data, thereby improving both sensitivity and selectivity compared to conventional spectrophotometric and chromatographic methods. The Marquis reagent, as a simple, known reagent, was used to acquire kinetic-spectrophotometric data for rank annihilation factor analysis of morphine in several unknown samples. Marquis reagent is composed of a mixture of formaldehyde and concentrated sulfuric acid. Usually, different compounds produce different color reactions when using this reagent. The proposed method was first investigated using simulated data before a couple of tested opiate samples were analyzed by the proposed method to further investigate its performance. The proposed method was also successfully applied to determine morphine in a human urine sample.
    Keywords:  Kinetic-spectrophotometric; Marquis reagent; Morphine; RAFA
    DOI:  https://doi.org/10.1038/s41598-025-97220-y
  11. STAR Protoc. 2025 Apr 05. pii: S2666-1667(25)00151-0. [Epub ahead of print]6(2): 103745
    Protocol for dual metabolomics and proteomics using nanoflow liquid chromatography-tandem mass spectrometry.
    Weiwei Lin, Fatemeh Mousavi, Benjamin C Blum, Christian F Heckendorf, Matthew Lawton, Noah Lampl, Ryan Hekman, Mark McComb, Andrew Emili.
      Nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS) benefits untargeted metabolomics by enhancing sensitivity and integrating proteomics for the same sample. Here, we present a protocol to enable nLC-MS for dual metabolomics and proteomics. We describe steps for solid-phase micro-extraction (SPME)-assisted metabolite cleaning and enrichment, which avoids capillary column blockage. We then detail nLC-MS data acquisition and analysis. This protocol has been applied in diverse specimens including biofluids, cell lines, and tissues. For complete details on the use and execution of this protocol, please refer to Lin et al.1.
    Keywords:  Bioinformatics; Mass Spectrometry; Metabolomics; Proteomics; Systems biology
    DOI:  https://doi.org/10.1016/j.xpro.2025.103745
  12. Clin Chem Lab Med. 2025 Apr 08.
    Liquid chromatography tandem mass spectrometry (LC-MS/MS) candidate reference measurement procedure for urine albumin.
    Seiei Shiba, Zoi E Sychev, Michael D Evans, Jesse C Seegmiller.
       OBJECTIVES: Urine albumin is a key biomarker utilized for diagnosis and monitoring progression of chronic kidney disease (CKD). These characteristics highlight the importance urine albumin serves in patient management. However, laboratory results are confounded by a lack of standardization where results may exceed 40 % difference between diagnostic platforms. This presents serious issues since current guideline clinical decision points are fixed values and misclassification may occur between laboratory methods. Therefore, standardization is needed for urine albumin measurements.
    METHODS: A liquid chromatography tandem mass spectrometry (LC-MS/MS) reference measurement procedure (RMP) was developed. This RMP employed proteolysis using trypsin and examined six peptides specific to human serum albumin. The National Institute of Standards and Technology 2925 reference material was used to value assign calibrators. To improve imprecision and accuracy, all samples were run in quadruplicate. Urine from 98 patient specimens was analyzed.
    RESULTS: RMP final results consisted of averaging four peptide transitions, yielding a 20-day coefficient of variation (CV) of <3.0 %. Factors considered in assigning RMP overall uncertainty included specimen and internal standard pipetting, calibration material, and LC-MS/MS imprecision. This RMP was compared to the Roche Cobas and Siemens Dimension Vista urine albumin assays and was found to have a -9.9 and 20.1 % bias, respectively. This RMP was found to have equivalent results to two other RMPs in a previous study.
    CONCLUSIONS: This RMP demonstrated excellent imprecision, achieving an overall CV of 2.8 % and meeting the CV ≤6.2 % performance specification required for standardizing urine albumin measurements in clinical laboratories.
    Keywords:  LC-MS/MS; mass spectrometry; reference measurement procedure; standardization; urine albumin
    DOI:  https://doi.org/10.1515/cclm-2024-1374
  13. J Mass Spectrom. 2025 May;60(5): e5130
    Comparison of Dip-it-DART-Orbitrap-MS With Nitrogen Plasma to HPLC/Orbitrap-MS in Profiling Aromatic Glycoconjugation in White Grapes.
    Mariusz Dziadas, Henryk Jeleń.
      Direct analysis of aromatic glycosidic precursors in plants has posed an analytical challenge for decades. Traditional techniques, such as SPE-GC/MS, primarily provided information on volatile aglycones released through hydrolysis. However, the application of high-resolution mass spectrometry combined with liquid chromatography has enabled the direct analysis of intact glycosides without the need for derivatization or hydrolysis. Advances in soft ionization methods, such as DART, offer a novel approach to exploring the hidden aromatic potential in grapes without chromatographic separation. In this work, we present a novel and rapid method for screening aromatic glycosidic precursors in white grapes using high-resolution mass spectrometry (Orbitrap) combined with the soft ionization DART method with nitrogen plasma. Optimization of N2-DART ionization parameters, including grid voltage, gas temperature, and Dip-it sampler speed, performed on selected synthetic glycosidic precursors, allowed the establishment of characteristic ionization patterns and evaluation of 15 groups of glycosidic precursors. The results from the profiling analysis using the N2-DART-Orbitrap-MS method are comparable to those obtained by HPLC/Orbitrap-MS method. This new analytical approach, N2-DART-Orbitrap-MS, reduces drastically analysis time by eliminating the need for chromatographic separation when screening glycoside precursors, uses a convenient Dip-it tips for sampling. It also allows for deeper exploration of ionization using nitrogen plasma, applied for the first time in the analysis of glycoside precursors, demonstrating the applicability of this method for the rapid characterization and screening of glycosidically bound aroma compounds in plants.
    Keywords:  DART; Orbitrap; Penning ionization; glycoside precursors; monoterpenes
    DOI:  https://doi.org/10.1002/jms.5130
  14. Anal Bioanal Chem. 2025 Apr 08.
    In-depth characterization of acylcarnitines: utilizing nitroxide radical-directed dissociation in tandem mass spectrometry.
    Xiangyu Gao, Xue Zhao.
      Acylcarnitines (ACs) are metabolic intermediates of fatty acids playing important roles in regulating cellular energy and lipid metabolism. The large structural diversity of ACs arises from variations in acyl chain length and the presence of chemical modifications, such as methyl branching, desaturation, hydroxylation, and carboxylation. Numerous studies have demonstrated that these structural isomers of ACs function as biomarkers for a variety of diseases. However, conventional tandem mass spectrometry (MS/MS) via low-energy collision-induced dissociation (CID) faces challenges in distinguishing these isomers. In this study, we report a radical-directed dissociation (RDD) approach for characterization of the intrachain modifications within ACs. The method involves derivatizing ACs with O-benzylhydroxylamine (O-BHA), followed by MS2 CID to produce a nitroxide radical for subsequent RDD along the fatty acyl chain. The above RDD approach was employed on a cyclic ion mobility spectrometry (cIMS) and reversed-phase liquid chromatography (RPLC), enabling the identification and relative quantification of branched chain isomers of ACs. By derivatizing carboxylated ACs with O-BHA, their mass is shifted to a higher region, thereby facilitating their separation from the isobars of hydroxylated ACs. Furthermore, this RDD method effectively allows for the assignment and localization of C = C and hydroxylation positions. This RDD approach has been applied for in-depth profiling of ACs in mice plasma extracts.
    Keywords:  Acylcarnitine; Liquid chromatography; Radical-directed dissociation; Tandem mass spectrometry
    DOI:  https://doi.org/10.1007/s00216-025-05868-2
  15. Int J Pharm. 2025 Apr 04. pii: S0378-5173(25)00391-6. [Epub ahead of print]675 125554
    Pharmacometabolomics: An emerging platform for understanding the pathophysiological processes and therapeutic interventions.
    Chandra Prakash, Pronami Moran, Rohit Mahar.
      Pharmacometabolomics has emerged as a new subclass of metabolomics, aiming to predict an individual's response to a drug or optimize therapy based on prior information on an individual's metabolic profile. Pharmacometabolomics is being explored in drug discovery, biomarker identification, disease diagnosis, monitoring of disease progression, and therapeutic intervention. The time points-based sample collection is essential to measure the response of individuals to pathophysiological processes and therapeutic interventions. Analytical techniques such as NMR, LC-MS, and GC-MS have been employed to assess a huge number of metabolites present in biological systems. NMR has an advantage over other analytical techniques as it provides a snapshot of tissue and biological fluids, however, it requires higher magnetic fields to achieve better resolution. GC-MS could cover a wide range of metabolites due to high resolution but requires derivatization for certain metabolites. LC-MS is equally competitive and separates a wide range of metabolites with diverse polarities but requires extensive method development. Several platforms have been developed to analyze the analytical data and provide meaningful results via data reduction methods. PCA and PLS-DA are the most common methods for reduction dimensionality through simplified multivariate data modeling. This manuscript brings insights into the overview of pharmacometabolomics experimental design and the application of various analytical techniques and multivariate statistical analysis in the various fields of medical research.
    Keywords:  Biomarker; LC/GC–MS; Multivariate Analysis; NMR; Pharmacometabolomics
    DOI:  https://doi.org/10.1016/j.ijpharm.2025.125554
  16. Front Pharmacol. 2025 ;16 1531496
    High-performance liquid chromatography-tandem mass spectrometry for simultaneous determination of 23 antidepressants and active metabolites in human serum and its application in therapeutic drug monitoring.
    Jinglong Wang, Junjie Wang, Chenxiao Zhang, Guofei Li.
       Introduction: The incidence and mortality rate from depression are increasing year by year, and depression has become the main cause of global health loss and disability. Currently, the treatment of depression mainly relies on drug intervention. However, the vast majority of antidepressants exhibit significant pharmacological variability, resulting in individual differences in steady-state blood drug concentrations even with the same dosing regimen among patients. Therefore, using therapeutic drug monitoring (TDM) to guide the precise use of antidepressants has important clinical significance.
    Methods: In this paper, we developed a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to study simultaneously TDM and clinical pharmacokinetics of 23 antidepressants and active metabolites: sertraline, escitalopram, fluvoxamine, paroxetine, duloxetine, milnacipran, fluoxetine, venlafaxine, O-desmethylvenlafaxine, mirtazapine, trazodone, bupropion, hydroxybupropione, norfluoxetine, vortioxetine, agomelatine, mianserin, doxepine, desmethyldoxepin, clomipramine, desmethylclomipramine, amitriptyline and nortriptyline hydrochloride. After protein precipitation of serum samples with acetonitrile, the isotope internal standards (ISs), antidepressants and active metabolites were separated using a ZORBAX Eclipse Plus C18 column (50.0 mm × 2.1 mm, 1.7 µm) with water containing 0.1% formic acid and 10 mmol/L ammonium acetate and methanol containing 0.1% formic acid. Validation of the developed method was carried out based on the Chinese Pharmacopoeia guidelines for bioanalytical method validation, including assessment of specificity, calibration curves, carryover, accuracy, crosstalk, precision, stability, recovery, dilution integrity and matrix effect.
    Results: The results showed that a simple, fast, reliable and specific HPLC'MS/MS method was developed and validated, and all the performance characteristics of the method met the requirements, which could be used to study TDM and pharmacokinetics of the above 23 antidepressants and active metabolites.
    Keywords:  HPLC; TDM; antidepressants; tandem mass spectrometry; validation
    DOI:  https://doi.org/10.3389/fphar.2025.1531496
  17. J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Apr 02. pii: S1570-0232(25)00132-1. [Epub ahead of print]1257 124580
    A rapid and sensitive LC-MS/MS method for the simultaneous determination of chlorfenapyr and its major metabolite tralopyril in human plasma: From method development, validation to clinical application.
    Shiyuan Tang, Shunjie Zhang, Hongling Du, Xia Yang, Qunmei Yao, Aihua Peng, Minghai Tang, Yu Cao.
      Chlorfenapyr (CFN), widely used as an insecticide, is a pro-insecticide that acts after being metabolized to the active metabolite tralopyril (TLP). In clinical practice, CFN poisoning is characterized by atypical symptoms, delayed toxicity and high mortality. The therapeutic importance of assessing TLP levels in the management of CFN poisoning has been demonstrated in recent clinical and toxicokinetic studies. Unfortunately, the simultaneous quantification of CFN and TLP poses technical challenges and is still lacking in clinical practice. In this study, a novel LC-MS/MS method was developed for rapid and accurate simultaneous analysis of CFN and TLP in human plasma within 3 min. Samples were extracted by acetonitrile protein precipitation. Stable CFN anionic adducts [M + HCOO]- were selected to provide satisfactory MS signals. To improve the signal and peak shape, the mobile phase was preferred to consisting of 2 mM ammonium formate containing 0.01 % ammonia and acetonitrile. The optimized multiple reaction monitoring transitions of m/z 451.0 → 346.9, 349.9 → 78.9 and 307.1 → 161.1 were selected in the negative ionization mode to detect CFN, TLP and IS (warfarin), respectively. The method demonstrated satisfactory linearity with low LLOQ (5 ng/mL for CFN and 1 ng/mL for TLP, respectively), and the precision and accuracy were acceptable. Both compounds showed good stability under relevant conditions. Furthermore, the method was successfully applied to 72 clinical plasma samples from 20 patients with CFN poisoning. The results showed that the concentration of TLP in plasma was significantly higher than that of CFN (P < 0.0001), and all five deaths demonstrated high TLP concentrations (>1000 ng/mL). These data demonstrate the potential relationship between toxins concentration and toxicity in CFN poisoning patients.
    Keywords:  Chlorfenapyr; Clinical poisoning; Clinical sample; LC–MS/MS; Tralopyril
    DOI:  https://doi.org/10.1016/j.jchromb.2025.124580
  18. Biomed Chromatogr. 2025 May;39(5): e70081
    Determination by UHPLC-QTOF-HRMS of Phosphatidylethanol (PEth) in Dried Blood Spots: Method Validation and Practical Application of a Rising Alcohol Abuse Biomarker With Minimally Invasive Sampling.
    Christina Ververi, Marta Massano, Eugenio Alladio, Alberto Salomone, Marco Vincenti.
      The goal of our study was to develop and validate a simple, quick, and sensitive method to detect phosphatidylethanol (PEth) in dried blood spots (DBS). A 30-μL aliquot of blood was collected on a DBS card and allowed to dry at room temperature. Then, the spot was cut and transferred into a clean tube where the internal standard (PEth-D5) and 1-mL hexane were added followed by stirring, sonication, and centrifugation at room temperature. The dried supernatant was reconstituted with 30-μL acetonitrile and analyzed by UHPLC-HRMS-QTOF. Calibration curve was created at 20, 50, 100, 200, 300, and 500 ng/mL; the limit of detection was calculated at 5 ng/mL (S/N > 3) while accuracy, precision, recovery, and matrix effect were successfully evaluated, along with the analyte stability at different time intervals and temperatures. The study demonstrates that quantifying PEth 16:0/18:1 from DBS cards is feasible using UHPLC-QTOF or UHPLC-QqQ instrumentation while the QTOF method was validated and proved reliable for PEth detection to assess both excessive alcohol consumption and alcohol abstinence, matching current guidelines. Preliminary data on authentic samples confirmed the method's performance in terms of ease, sustainability, and speed, supporting its great potential for routine toxicological diagnosis of chronic alcohol abuse.
    Keywords:  DBS; PEth; Q‐TOF; alcohol abuse; dried blood spot
    DOI:  https://doi.org/10.1002/bmc.70081
  19. J Proteome Res. 2025 Apr 08.
    MSIght: A Modular Platform for Improved Confidence in Global, Untargeted Mass Spectrometry Imaging Annotation.
    Lauren Fields, Hannah N Miles, Alexis E Adrian, Elliot Patrenets, William A Ricke, Lingjun Li.
      Mass spectrometry imaging (MSI) has gained popularity in clinical analyses due to its high sensitivity, specificity, and throughput. However, global profiling experiments are often still restricted to LC-MS/MS analyses that lack spatial localization due to low-throughput methods for on-tissue peptide identification and confirmation. Additionally, the integration of parallel LC-MS/MS peptide confirmation, as well as histological stains for accurate mapping of identifications, presents a large bottleneck for data analysis, limiting throughput for untargeted profiling experiments. Here, we present a novel platform, termed MSIght, which automates the integration of these multiple modalities into an accessible and modular platform. Histological stains of tissue sections are coregistered to their respective MSI data sets to improve spatial localization and resolution of identified peptides. MS/MS peptide identifications via untargeted LC-MS/MS are used to confirm putative MSI identifications, thus generating MS images with greater confidence in a high-throughput, global manner. This platform has the potential to enable large-scale clinical cohorts to utilize MSI in the future for global proteomic profiling that uncovers novel biomarkers in a spatially resolved manner, thus widely expanding the utility of MSI in clinical discovery.
    Keywords:  MALDI; Python; histology; imaging software; mass spectrometry imaging; multimodal imaging; spatial omics
    DOI:  https://doi.org/10.1021/acs.jproteome.4c01140
  20. Anal Chem. 2025 Apr 10.
    Towards Generalizable In Silico Predictions of Differential Ion Mobility Using Machine Learning and Customized Fingerprint Engineering.
    Cailum M K Stienstra, Christopher R M Ryan, Daniel Demczuk, Justine R Bissonnette, Anish Arjuna, J Larry Campbell, W Scott Hopkins.
      Differential mobility spectrometry (DMS), a tool for separating chemically similar species (including isomers), is readily coupled to mass spectrometry to improve selectivity in analytical workflows. DMS dispersion curves, which describe the dynamic mobility experienced by an ion in a gaseous environment, show the maximum ion transmission for an analyte through the DMS instrument as a function of the separation voltage (SV) and compensation voltage (CV) conditions. To date, there exists no fast, general prediction tool for the dispersion behavior of ions. Here, we demonstrate a machine learning (ML) model that achieves generalized dispersion prediction using an in silico feature addition pipeline. We employ a data set containing 1141 dispersion curve measurements of anions and cations recorded in pure N2 environments and in N2 environments doped with 1.5% methanol (MeOH). Our feature addition pipeline can compute 1591 RDKit and Mordred descriptors using only SMILES codes, which are then normalized to sampled molecular distributions (n = 100 000) using cumulative density functions (CDFs). This tool can be thought of as a "learned" feature fingerprint generation pipeline, which could be applied to almost any molecular (bio)cheminformatics tasks. Our best performing model, which for the first time considers solvent-modified environments, has a mean absolute error (MAE) of 2.1 ± 0.2 V for dispersion curve prediction, a significant improvement over the previous state-of-the-art work. We use explainability techniques (e.g., SHAP analysis) to show that this feature addition pipeline is a semideterministic process for feature sets, and we discuss "best practices" to understand feature sets and maximize model performance. We expect that this tool could be used for prescreening to accelerate or even automate the use of DMS in complex analytical workflows (e.g., 2D LC×DMS separation) and perform automated identification of transmission windows and increase the "self-driving" potential of the instrument. We make our models available as a free and accessible tool at https://github.com/HopkinsLaboratory/DispersionCurveGUI.
    DOI:  https://doi.org/10.1021/acs.analchem.5c00737
  21. Anal Methods. 2025 Apr 11.
    Preparation of multicellular spheroid sections embedded with sodium carboxymethyl cellulose for mass spectrometry imaging.
    Xin Wang, Xuantong Liu, Chao Zhao, Zhiyi Yang, Tianyou Cao, Qian Luo, Wei Bian.
      Compared with organic analysis, mass spectrometry imaging (MSI)-based cellular localization and molecular information investigations are rapidly becoming crucial tools in tumor research, drug screening, and toxicity testing. Fresh-frozen sections are ideal for MSI because they offer much better integrity of biological information than formalin-fixed paraffin-embedded (FFPE) sections. However, the suitable sample preparation method, especially to ensure the acquisition of intact sections from cell samples, is critical and has significant effects on MSI application. Herein, we optimized the embedding approaches and developed a thin and transparent cryoplatform using 2% sodium carboxymethyl cellulose (CMC) to prepare high-quality sections of three-dimensional heterogeneous multicellular tumor spheroids (3D heterogeneous MCTSs) for morphological and MSI analyses. More specifically, four embedding approaches, including the use of 2% CMC, optimum cutting temperature embedding medium (OCT), polyvinylpyrrolidone-hydroxypropyl methylcellulose (PVP-HPMC), and CMC-sucrose, were systematically evaluated regarding sample integrity, lipid signal interference, and lipid distributions. Among these, the 2% CMC and PVP-HPMC embedding methods exhibited optimal performance characteristics for morphological and matrix-assisted laser desorption/ionization (MALDI)-MSI analyses. More importantly, these two methods accurately highlighted the heterogeneity of the MCTSs in terms of morphological staining, spatial segmentation, and spatial distribution of lipids, including the necrotic and proliferative micro-areas. This approach allowed assessments of the metabolite expressions at the inter-cellular level, showing that phosphatidylglycerol (PG) (34 : 2), PG (32 : 1), and phosphatidylcholine (PC) (34 : 1) were enriched in the proliferative areas, while phosphatidylinositol (PI) (38 : 5), phosphatidylserine (PS) (40 : 4), and PI (38 : 4) were predominantly located in the necrotic regions. In summary, our method for preparing cell samples has greatly broadened the application range of MSI detection and allows for the extraction of more biological and pathological information associated with tumor research.
    DOI:  https://doi.org/10.1039/d5ay00022j
  22. Drug Test Anal. 2025 Apr 10.
    Optimization of Parallel Artificial Liquid Membrane Extraction for the Determination of Over 50 Psychoactive Substances in Oral Fluid Through UHPLC-MS/MS.
    Martina Croce, Camilla Montesano, Ilenia Bracaglia, Francesco Bartolini, Marcello Mascini, Dario Compagnone, Manuel Sergi.
      Over the past decade, there has been a diversification of the psychoactive substances available among drug users, resulting in the expansion of a dynamic market of synthetic molecules that are challenging for drug of abuse testing. Multiclass analytical methods are useful to deal with these new psychoactive substances (NPS), but sample preparation can be difficult and generate significant amounts of chemical waste. The aim of this work was the development of a high-throughput microextraction method for the determination of 56 drugs belonging to different pharmacological classes in oral fluid (OF), including both traditional drugs and NPS. In the proposed workflow, the OF sample is cleaned-up by parallel artificial liquid membrane extraction (PALME) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two hundred microliters of OF are mixed with 1800 μL of carbonate buffer 0.5 M (pH 12) and 0.4 g of sodium chloride and inserted into a donor plate; the acceptor plate embed a dodecylacetate-supported liquid membrane and an acceptor solution composed of 50 μL formic acid 0.1% in H2O: MeOH, 80:20 (v/v); the whole assemblage is placed on an orbital shaker for 120 min for extraction. A full factorial design has been employed for extraction optimization to make it suitable for LC-MS/MS. The developed method is an example of green chemistry and may be used for screening and quantitative purposes, with limits of detection ranging from 0.01 to 1.5 ng mL-1 and optimal performance in term of precision and accuracy for 49 out of 56 drugs tested.
    Keywords:  full factorial design; liquid chromatography‐mass spectrometry; oral fluid; parallel assisted liquid membrane extraction; psychoactive substances
    DOI:  https://doi.org/10.1002/dta.3894
  23. J Pharm Biomed Anal. 2025 Mar 29. pii: S0731-7085(25)00187-6. [Epub ahead of print]261 116846
    Simultaneous quantification of methotrexate, 7-hydroxymethotrexate and creatinine in serum by LC-MS/MS for predicting delayed elimination.
    Yingying Feng, Chunzi Li, Wei Xia, Yumei Pei, Chang Sun, Haiwei Cao, Zhengchao Ji, Jing Huang, Yanyan Li.
      High-dose methotrexate (HDMTX) is widely accepted as the first-line chemotherapeutic agent for pediatric acute lymphoblastic leukemia (ALL). However, it exhibits significant pharmacokinetic variability among individuals, which may lead to delayed elimination of MTX. In this study, we innovatively developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of serum MTX, 7-hydroxymethotrexate (7-OHMTX) and creatinine. The analytes were isolated using a protein precipitation method and separated on an Agilent Poroshell 120 SB-C18 column (4.6 × 50 mm, 2.7 µm) using a gradient elution with methanol (B) and 0.1 % formic acid in water (A), at a flow rate of 0.5 mL/min. The assay was linear over the range of 20-2000 ng/mL (R2 ≥ 0.997) for MTX and 7-OHMTX and 1-70 μg/mL (R2 ≥ 0.997) for creatinine. Intra- and inter-day accuracy for all analytes ranged from 88.1 % to 109.8 % with corresponding precision of 1.0-14.5 %. No significant matrix effects were observed, and analyses were extracted from human serum with recoveries exceeding 93.4 %. The predictive performance of the MTX48 h, 7-OHMTX48 h, the 7-OHMTX/MTX48 h ratio, creatinine48 h and the combined test value of the four indicators was evaluated using area under the curve (AUC). Receiver operating characteristic (ROC) analysis revealed that MTX48 h exhibited superior predictive accuracy with sensitivity of 87.5 %, specificity of 93.1 % and AUC of 0.914 compared to 7-OHMTX48 h with a sensitivity of 50.0 %, specificity of 89.7 % and AUC of 0.683. This finding suggesting that MTX48 h is a better predictor of delayed elimination than 7-OHMTX48 h. The 7-OHMTX/MTX48 h ratio provide a more reliable prediction of delayed elimination compared to 7-OHMTX48 h alone, emphasizing the importance of metabolic rates in addition to concentration levels. The combined test values of these four indicators at 48 h demonstrated higher predictive accuracy with sensitivity of 93.8 %, specificity of 96.6 % and AUC of 0.963 than any individual index with sensitivity (ranging from 50.0 % to 87.5 %), specificity (ranging from 79.3 % to 93.1 %) and AUC (ranging from 0.683 to 0.914). Notably, this combined test identified delayed elimination at 48 h rather than 72 h, thus enabling timely adjustments to calcium folinate rescue regimens.
    Keywords:  7-hydroxymethotrexate; Liquid chromatography-tandem mass spectrometry; Methotrexate; Serum creatinine; Therapeutic drug monitoring
    DOI:  https://doi.org/10.1016/j.jpba.2025.116846
  24. J Am Soc Mass Spectrom. 2025 Apr 05.
    Internal Standard Utilization Strategies for Quantitative Paper Spray Mass Spectrometry.
    Lucas R Abruzzi, John-Clare Laxton, Taelor M Zarkovic, Chris G Gill.
      Premixing internal standards (ISTD) with liquid samples prior to paper spray mass spectrometry (PS-MS) analysis consumes unnecessary amounts of ISTD and is not feasible for all sample types and applications. Depositing ISTD directly on the paper independently from sample has been successfully employed in the literature but can negatively affect quantitative performance. We evaluated different ISTD utilization strategies using drugs of misuse as test analytes to investigate the sources of irreproducibility and bias. Performance was assessed using both pre- and postdeposited ISTD (relative to sample loading) at different volumes with a constant final mass loading of 1 ng of each ISTD compound. Precision and accuracy were lower when using independently deposited ISTD compared to premixed ISTD (average CV = 18% vs 1% and average |bias| = 61% vs 5% for independently deposited ISTD and premixed ISTD, respectively). The use of a robotic liquid sample handling system to deposit ISTD was compared with results obtained via manually pipetting. Predeposited ISTD performed best at lower deposition volumes when a robotic liquid handler was used (average CV = 8% and 11% for 2 and 10 μL, respectively), but manual pipetting of low volume ISTD depositions performed poorly. Postdeposited ISTD was inferior to predeposited ISTD strategies, favoring larger deposition volumes regardless of deposition method (average CV = 22% and 16% for 2 and 10 μL, respectively). Systematic biases associated with each ISTD utilization strategy were effectively corrected for using strategy-matched calibrations, and AAFS (American Academy of Forensic Sciences) accuracy and precision requirements were achieved in almost all cases.
    Keywords:  internal standard; liquid sample handling; paper spray mass spectrometry; point-of-care analyses; sample preparation
    DOI:  https://doi.org/10.1021/jasms.5c00036
  25. Angew Chem Int Ed Engl. 2025 Apr 09. e202504080
    Building a Bridge Between Ambient MS and LC-MS by Non-Exhaustive Microdesorption.
    Wei Zhou, Janusz Pawliszyn.
      Ambient mass spectrometry (AMS) offers rapid screening but faces challenges in analyzing complex samples due to high matrix effects and limited selectivity. The absence of a separation step can also lead to false positives due to the isomers or isobars. In this study, a sequential analysis strategy which combines ambient MS and LC-MS was developed for the first time based on the non-exhaustive microdesorption in solid-phase microextraction (SPME). This strategy was demonstrated by combining coated blade spray (CBS)-MS with LC-MS. In the first step, a few microliters of solvent was used for non-exhaustive desorption with high enrichment factor for rapid screening by CBS-MS. For the suspicious samples, the remaining analytes on the SPME coating undergo exhaustive desorption, then followed by LC-MS confirmation. The matrix-compatible coating used in the SPME device significantly reduces matrix effects while enhancing sensitivity through analyte enrichment. This method is environmentally friendly, utilizing only a few microliters of organic solvents for screening. The approach was rigorously validated, both theoretically and experimentally, and successfully applied to anti-doping testing, enabling detection of 53 prohibited substances in urine samples by integrating CBS-MS with LC-MS.
    Keywords:  Solid-phase microextraction * Ambient MS * Sequential analysis * Rapid screening * Anti-doping
    DOI:  https://doi.org/10.1002/anie.202504080
  26. Semin Nephrol. 2025 Apr 09. pii: S0270-9295(25)00018-X. [Epub ahead of print] 151581
    Spatial Glycomics and Kidney Disease.
    Dušan Veličković, Christopher R Anderton.
      Glycans are critical for the kidney's physiological and pathological cellular functions, and our ability to see their spatial distributions within tissues has helped us reveal how these carbohydrate moieties are involved in many of these processes. This review discusses the role of different types of glycans in kidney biology and disease, common approaches used for glycan imaging, and how glycan imaging has helped us better understand kidney pathology. We mainly focus on emerging methods using mass spectrometry imaging (MSI) because this technology is untargeted and provides complete information on glycan composition compared to the other methods, such as lectin and metabolite labeling, which are targeted and often inform only on the specific part of a glycan structure. We especially focus on protein N-glycosylation, as this is one of the most common post-translational modifications, and these moieties play a vital role in renal structure and function. The recent advancements in MSI of N-glycans we reviewed have provided new insights into the pathophysiology of the kidney and paved the way for clinical application. Semin Nephrol 36:x-xx © 20xx Elsevier Inc. All rights reserved.
    Keywords:  Glycans; N-glycosylation; lectin staining; mass spectrometry; metabolite labeling
    DOI:  https://doi.org/10.1016/j.semnephrol.2025.151581
  27. Angew Chem Int Ed Engl. 2025 Apr 11. e202502028
    Integrating Ambient Ionization Mass Spectrometry Imaging and Spatial Transcriptomics on the Same Cancer Tissues to Identify Gene-Metabolite Correlations.
    Trevor M Godfrey, Yasmin Shanneik, Wanqiu Zhang, Thao Tran, Nico Verbeeck, Nathan H Patterson, Faith E Jackobs, Chandandeep Nagi, Maheshwari Ramineni, Livia Schiavinato Eberlin.
      Innovations in spatial omics technologies applied to human tissues have led to breakthrough discoveries in various diseases, including cancer. Two of these approaches - spatial transcriptomics and spatial metabolomics - have blossomed independently, fueled by technologies such as spatial transcriptomics (ST) and mass spectrometry imaging (MSI). While powerful, these technologies only offer insights into the spatial distributions of restricted classes of molecules and have not yet been integrated to provide more holistic insights into biological questions. These techniques can be performed on adjacent serial sections from the same sample, but section-to-section variability can convolute data integration. We present a novel method combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) spatial metabolomics and Visium spatial transcriptomics on the same tissue sections. We show that RNA quality is maintained after performing DESI-MSI on a tissue and that ST data is unperturbed following DESI-MSI. We demonstrate this workflow on human breast and lung cancer tissues and identify novel correlations between metabolites and RNA transcripts in cancer specific regions.
    Keywords:  tissue imaging mass spectrometry imaging spatial transcriptomics cancer research disease markers
    DOI:  https://doi.org/10.1002/anie.202502028
  28. Anal Chem. 2025 Apr 11.
    RapidMass: A Graphical Data Processing Application for Automated Species Authentication in High-Throughput Mass Spectrometry.
    Chunxiang Liu, Qian Meng, Yun Li, Hanze Wang, Huanya Yang, Huiting Ou, Saiyi Ye, Changliang Yao, Qirui Bi, Wenlong Wei, Jianqing Zhang, Dean Guo.
      High-throughput mass spectrometry (HT-MS) facilitates rapid, large-scale data acquisition, providing a fast and efficient solution for various analytical challenges. However, the increasing volume of data generated by MS requires automation and easy-to-use processing tools. Currently, there is no freely available software that is compatible with most instruments for species authentication or classification. Here, we introduce RapidMass, a cutting-edge software platform designed to automate the handling, evaluation, presentation, and management of HT-MS data for species identification. Key features include a streamlined workflow for processing spectra from various instruments (e.g., DI-MS, ASAP-MS, DART-MS), three specialized algorithms for scoring unknown samples, peak annotation review, visualization of MS1 and MS2 spectra, and an expandable personal database for customized data management. Performance validation conducted on nine data sets covering diverse sample compositions, instrument types, suppliers, resolutions, and MS acquisition modes, demonstrated RapidMass's excellent performance, with processing times of 12 to 20 s per sample and authentication accuracies ranging from 97% to 100% for easily confused plants. With its user-friendly interface, RapidMass empowers users to create and manage personalized databases, presenting significant prospects for broad applications across various fields.
    DOI:  https://doi.org/10.1021/acs.analchem.4c05062
  29. SLAS Technol. 2025 Apr 09. pii: S2472-6303(25)00047-0. [Epub ahead of print] 100289
    An ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of deoxycholic acid and application to a pharmacokinetic study in human plasma.
    Wanlin Xi, Diyi Fu, Ni Wu, Fei Liu, Cuixia Zhang, Ruijie Wan, Zhen Wu, Rui Chen, Qian Zhao.
      Deoxycholic acid (DCA) injection is applied in treating moderate to severe submental bulge or facial fullness caused by excessive submental fat accumulation. Utilizing the method known as ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), which was swiftly, precisely, and reliably confirmed, DCA was determined in human plasma with low quantification limits of 56 ng/mL. We selected six healthy individual blank human plasma with low concentrations of endogenous deoxycholic acid and mixed them to prepare standard curve samples. The materials were purified by means of protein hydrolysis and subsequently separated using a BEH C18 column (2.1 × 50 mm, 1.7 µm). The experiment employed multiple reaction monitoring (MRM) and ESI sources operating in negative mode, the mass was identified and measured. The precursor to ionic charge transfer was observed at m/z 391.2- → 345.2- and m/z 395.2- → 349.2- for DCA and DCA-d4 (isotope internal standard), respectively. The method was subjected to comprehensive assessment, encompassing evaluations of linearity, sensitivity, reproducibility, selectivity, robustness, matrix effect, accuracy, carryover and recovery. In a word, the validation results showed that this model demonstrated reliability, accuracy, and precision, and could be effectively used to study the pharmacokinetic properties of DCA in a randomised, parallel, controlled, phase I clinical trial.
    Keywords:  Deoxycholic acid; Drug metabolism; Human plasma; UPLC–MS/MS
    DOI:  https://doi.org/10.1016/j.slast.2025.100289
  30. J Phys Chem A. 2025 Apr 07.
    Comprehensive and Explainable Fragmentation: A Machine Learning Approach for Fast and Accurate Mass Spectrum Prediction.
    Xian-Yang Zhang, Xue-Qing Gong.
      Mass spectrometry (MS) is a fundamental tool for chemical identification. The current in-silico prediction tools can handle broad instrument conditions, large molecular libraries or fragment structures only on a very limited level. In this work, we propose a dual-model machine learning strategy that can solve this problem by jointly a classification model for fragment identification and noise filtering, and a regression model for spectral prediction. With the help of attention mechanism, our method outperforms other algorithms in accuracy and efficiency, providing a deeper understanding of the molecular fragmentation behavior in mass spectra. Our method can facilitate the large-scale in-silico spectra calculations and the analysis of unknown molecular structures, which may promote wider applications for MS.
    DOI:  https://doi.org/10.1021/acs.jpca.4c08663
  31. Talanta. 2025 Mar 26. pii: S0039-9140(25)00478-3. [Epub ahead of print]293 127988
    Innovation in venlafaxine detection: Development and application of electroanalytical method using a boron-doped diamond electrode and performance comparison with UHPLC-MS/MS.
    Arielly Cardoso, Ana Carolina Maia Fraga, Mayara da Silva Araujo, Roberto de Matos, César Ricardo Teixeira Tarley, Cintia Stefhany Ripke Ferreira, Oscar Oliveira Santos, Roberta Antigo Medeiros.
      Venlafaxine hydrochloride (VEN) is a commonly used antidepressant that acts on monoamines, helping to regulate and enhance neurotransmitter levels in the body. However, due to its widespread use, VEN has been classified as an emerging contaminant, raising significant environmental concerns because of the risks it poses to ecosystems. In this context, we propose the development of a simple and rapid electroanalytical method for determining VEN, validated against the results obtained using the ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. The electroanalytical method employed batch injection analysis with amperometric detection (BIA-AMP) and a boron-doped diamond (BDD) electrode as the working electrode. The linear concentration range achieved was 8.30-277.40 μg L-1 (0,029 to 1.00 μmol L-1), with a limit of detection (LOD) of 1.03 μg L-1 (3.71 nmol L-1). The UHPLC-MS/MS method provided a linear concentration range of 7.00-1000 ng L-1 (0.025-3.60 nmol L-1) and a LOD of 7.0 ng L-1 (0.025 nmol L-1). Spiking and recovery studies demonstrated that VEN can be accurately determined using these analytical methods without significant matrix effects. The BIA-AMP method demonstrates a more environmentally friendly profile compared to UHPLC-MS/MS, as assessed using the AGREE software. It is simple, rapid (22 determinations per hour), does not require organic and/or toxic solvents, consumes less energy, and allows for the possibility of reliable analyses.
    Keywords:  Antidepressants; Electroanalytical method; Emerging contaminant; Environmentally friendly method; Ultra-high performance liquid chromatography; Venlafaxine
    DOI:  https://doi.org/10.1016/j.talanta.2025.127988
  32. Bioanalysis. 2025 Apr 09. 1-12
    Regulated bioanalysis of antibody-drug conjugates using LC-MS.
    Katsunori Ieki, Suguru Fukuda, Shiori Miyawaki, Kazunari Hirowatari.
      Antibody-drug conjugates (ADCs) are emerging as powerful tools in cancer therapy. Evaluating their drug disposition requires the development and validation of analytical methods to obtain accurate quantitative results, which depend on understanding the ADC structural properties and selecting appropriate analytical platforms. Liquid chromatography-mass spectrometry (LC-MS) is a key technology for ADC bioanalysis, enabling the quantification of payloads, linkers, total antibodies, ADCs, and drug-to-antibody ratio (DAR). This review highlights the strategies and challenges in developing analytical methods for quantifying ADC components in biological samples using LC-MS with a focus on their constituent units. In addition, it addresses the validation requirements of these quantitative analytical methods during drug development.
    Keywords:  ADC; DAR; LC-MS; conjugated antibody; payload; total antibody; validation
    DOI:  https://doi.org/10.1080/17576180.2025.2490468
  33. J Chromatogr A. 2025 Apr 03. pii: S0021-9673(25)00287-0. [Epub ahead of print]1750 465939
    An ultra-high-performance tandem mass spectrometry method to quantify tryptophan metabolites in aqueous humor of primary angle-closure glaucoma patients.
    Xingang Fu, Weiwei Guo, Yuheng Cheng, Lin Li.
      This study presented the development and validation of a robust ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of tryptophan (TRP) and its nine metabolites in aqueous humor (AH) to explore the regulation of the TRP metabolic pathway in primary angle-closure glaucoma (PACG). The optimized UPLC-MS/MS method demonstrated good linearity (R² > 0.99), sensitivity (LLMI: 0.11 - 1.31 ng/mL), precision (CVs: 2.18 % and 12.88 %), recovery rates (85.06 % - 105.74 %), bench-top, long-term and on-instrument stabilities (CVs: 2.35 % - 6.88 %). The validated UPLC-MS/MS method was applied to AH samples from PACG patients with cataract and cataract-alone patients. The results showed that kynurenine and 3-hydroxykynurenine concentrations were significantly increased in the AH of the PACG group, indicating up-regulated indoleamine 2,3-dioxygenase activity and a metabolic shift towards the production of the neurotoxic metabolites within the kynurenine pathway. These findings underscore the potential involvement of TRP metabolism in PACG pathogenesis.
    Keywords:  Aqueous humor; Kynurenine pathway; Primary angle-closure glaucoma; UPLC-MS/MS
    DOI:  https://doi.org/10.1016/j.chroma.2025.465939
  34. J Am Soc Mass Spectrom. 2025 Apr 07.
    Distinguishing the Metabolic Effect of Fetal and Adult Fibrinogen on Human Fibroblast Cell Culture by IR-MALDESI Mass Spectrometry Imaging.
    Alena N Joignant, Anastasia Sheridan, Ashley C Brown, David C Muddiman.
      Mass spectrometry imaging (MSI) of cells can elucidate metabolic changes with cellular and molecular specificity. Fibroblasts are mesenchymal cells that are important in tissue homeostasis and wound healing. During early wound healing, fibroblasts adhere to fibrinogen and migrate into fibrin clots, which are important interactions to stabilize early blood clots and promote subsequent tissue remodeling. It is understood that fibrinogen exists in distinct forms, fetal and adult, which have differing glycosylation and morphological effects on fibroblasts. Despite their importance to wound healing and the extracellular environment, fibroblasts are not commonly studied by MSI. While many MSI studies are conducted at the single-cell or subcellular level, there is still utility in accessing a broad view of the metabolic changes in a cell culture above single-cell spatial resolution. This enables imaging a wider area and larger number of cells directly from cell culture. In this work, dermal fibroblasts were imaged directly from cell culture chamber slides by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI). This method enabled treating the chambers with adult or fetal fibrinogen prior to cell culture and reduced sample preparation prior to MSI. Many metabolic effects of serum and fibrinogen type were elucidated, with changes in many membrane lipids such as cholesterol and ceramides potentially contributing to the observed morphological effects of fibrinogen types on fibroblasts.
    Keywords:  IR-MALDESI; fibrinogen; fibroblast; mass spectrometry imaging
    DOI:  https://doi.org/10.1021/jasms.5c00027
  35. Talanta. 2025 Apr 09. pii: S0039-9140(25)00589-2. [Epub ahead of print]293 128099
    Electrophoresis-enhanced paper spray mass spectrometry.
    Dylan T Holden, Brison A Shira, MyPhuong T Le, R Graham Cooks.
      The development of ambient ionization methods, such as paper spray (PS), has streamlined the transition from a collection of molecules in a condensed-phase sample to the gas-phase ions represented in a mass spectrum. In many cases, time and resources are saved by omitting chromatography and sample preparation; yet this strategy also eliminates the opportunity to process mixtures in the condensed phase. We here report a PS method that, without additional hardware or expertise, enhances mass spectrometry (MS) analysis of mixtures through electrophoresis. By loading analyte solution onto pre-wetted paper and applying spray potential, analytes were spatiotemporally processed according to their electrophoretic mobility before being subjected to MS. The fundamental and analytical aspects of this electrophoresis-enhanced PS (EePS) were probed with polarity switching, pH changes, complex environmental matrices, and a variety of analytes, including natural products obtained directly from plant material, without chromatography. EePS provides only modest separations but exhibits wide pH tolerance, high compatibility with complex environmental matrices, excellent robustness, superb cost-effectiveness, and is amenable to novel mass analysis strategies using portable mass spectrometers in situ.
    Keywords:  Ambient ionization; Complex matrices; Electrophoresis; Environmental analysis; Mixture analysis; Natural products
    DOI:  https://doi.org/10.1016/j.talanta.2025.128099
  36. Biomed Chromatogr. 2025 May;39(5): e70079
    Metabolomic Profiling of Three Body Fluids Differentiates UWS and MCS in Disorders of Consciousness.
    Aiwei Wang, Long Xu, Fei Xue, Hezhen Lu, Xiaoyan Liu, Haidan Sun, Zhengguang Guo, Qianqian Ge, Xiaoli Geng, Xueling Chen, Binbin Zhang, Jiameng Sun, Feng Qi, Xia Niu, Ying Lan, Jianghong He, Wei Sun.
      Disorders of consciousness (DOC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), are complex brain dysfunctions with various causes. Misdiagnosis is common when relying solely on neurological exams, highlighting the need for accurate differentiation to guide clinical rehabilitation. This study explores metabolomic differences between UWS and MCS across cerebrospinal fluid (CSF), serum, and urine samples to identify biomarkers and metabolic pathways. Fifty-one subjects were categorized into UWS (n = 35) and MCS (n = 16) based on coma recovery scale-revised (CRS-R) scores. Ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to analyze samples, and statistical methods identified 14, 24, and 22 differential metabolites in CSF, serum, and urine, respectively. CSF metabolites were linked to necrosis, apoptosis, and neuroprotection; serum metabolites to lipid metabolism and immune response; and urine metabolites to cell signaling and neural function. Metabolomic panels showed AUC values of 0.85 (95% CI: 0.73-0.96) for CSF (95% CI: 0.86-1.00), 0.94 for serum, and 0.93 (95% CI: 0.79-1.00) for urine in distinguishing UWS from MCS. This profiling offers valuable insights into DOC pathophysiology and aids in accurate differentiation of these states.
    Keywords:  UPLC‐MS/MS; disorders of consciousness; fluid biomarkers; minimally conscious state; unresponsive wakefulness syndrome
    DOI:  https://doi.org/10.1002/bmc.70079
  37. Anal Chem. 2025 Apr 10.
    Harmonization of FT-ICR-MS Instruments for Interoperable Multi-Laboratory Comprehensive Compositional Profiling.
    Stefan A Pieczonka, Mary J Thomas, Philippe Schmitt-Kopplin, James W Marshall.
      Given the long hardware lifespan, fixed installation, and comparatively high investment required to procure them, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) instruments tend to have a long operational life. The field is constantly evolving with rapidly advancing instrumental developments, and FT-ICR research groups work with a range of instrument designs from different generations. Consequently, compositional spectra comparability between instruments is a critical concern in FT-ICR-MS, particularly due to the variability introduced by commonly used direct infusion methods. This study demonstrates interlaboratory comparability of FT-ICR-MS molecular profiles using a 12 T solariX with an Infinity Cell and a 7 T scimaX with a ParaCell, with closely matched sample introduction and ion guide systems. Using analytically challenging pet food samples, we achieved similar instrument performance metrics, including resolving power, mass error, feature count, signal-to-noise ratios, and m/z distribution. The improved field homogeneity and sensitivity of the ParaCell reduced ICR cell space-charge interferences, making specialized calibration methods beyond linear calibration obsolete. We observed up to 78% overlap in annotated signals of the spectra increasing to 95%, when higher-intensity features are considered. Relative abundances showed great similarity, despite sample-dependent fluctuations (median coefficient of variation 23.4% to 49.2% and 15.5% to 29.5%, respectively). Unsupervised multivariate analysis (PCA) revealed consistent sample profiles with no systematic bias. Our study demonstrates that with careful instrument adjustment, molecular profile comparability can be achieved, ensuring the continued relevance of extensive databases and large chemical data sets acquired in long-term and collaborative projects measured on different instrumentation.
    DOI:  https://doi.org/10.1021/acs.analchem.5c00488
  38. J Biol Methods. 2025 ;12(1): e99010049
    Lipidomics and temporal-spatial distribution of organelle lipid.
    Wenjuan Qian, Huiru Tang, Hongyan Yao.
       Background: Lipids are crucial signaling molecules or cellular membrane components orchestrating biological processes. To gain insights into lipid functions and the communication between organelles, it is essential to understand the subcellular localization of individual lipids. Advancements in lipid quantification techniques, improvements in chemical and spatial resolution for detecting various lipid species, and enhancements in organelle isolation speed have allowed for profiling of the organelle lipidome, capturing its temporal-spatial distribution.
    Objective: This review examined approaches used to develop organelle lipidome and aimed to gain insights into cellular lipid homeostasis from an organelle perspective. In addition, this review discussed the advancements in lipid-mediated inter-organelle communication within complex physiological and pathological processes.
    Conclusion: With the advancement of lipidomic technologies, more detailed explorations of organelle structures and the specific lipid-mediating functions they perform are feasible.
    Keywords:  Cellular lipid homeostasis; Inter-organelle communication; Lipidomics; Organelle isolation; Organelle lipid distribution
    DOI:  https://doi.org/10.14440/jbm.2025.0094
  39. J Mass Spectrom. 2025 May;60(5): e5135
    Development of High-Throughput Quantitative Imaging Mass Spectrometry for Analysis of Drug Distribution in Tissues.
    Yukari Tanaka.
      Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) is applied in drug discovery and development. A high-throughput quantitative MALDI-IMS methodology was developed to confirm whether epertinib is superior to lapatinib in penetrating brain metastases using intraventricular injection mouse models (IVMs) of human EGFR2 (HER2)-positive breast or T790M-EGFR-positive lung cancer cells. A simple calibration curve was prepared for each compound via spotting standard solutions without using blank tissue sections or blank tissues onto the same glass slide as the epertinib or lapatinib brain section samples. Quantitative MALDI-IMS was performed via coating a glass slide with a MALDI matrix solution containing each internal standard solution. The samples of calibration curve and brain section were analyzed using a linear ion trap mass spectrometer with a MALDI ion source. Epertinib and lapatinib responses were strongly linear, with a wide dynamic range and low variation (relative standard deviation [RSD] < 20%) among the individual concentrations. Epertinib and lapatinib were sufficiently extracted from brain sections after oral administration in a breast cancer IVM. The quantitative MALDI-IMS results revealed that the epertinib concentrations administered to the brain sections in the lung cancer IVM were similar to those measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Quantitative MALDI-IMS, owing to its high reproducibility and throughput, is useful for selecting drug candidates in the early stages of discovery and development, enabling efficient and rapid screening of candidate compounds as well as an understanding of the mechanisms of drug efficacy, toxicity, and pharmacokinetics/pharmacodynamics.
    Keywords:  MALDI; epertinib; high‐throughput; lapatinib; quantitative imaging mass spectrometry
    DOI:  https://doi.org/10.1002/jms.5135
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