bims-metlip 2025-07-27 papers

bims-metlip

Biomed News

on Methods and protocols in metabolomics and lipidomics

Issue of 2025–07–27
23 papers selected by
Sofia Costa, Matterworks

Development and Validation of a Rapid LC-MS/MS Method for Plasma Analysis of Ketamine, Norketamine, Dehydronorketamine, and Hydroxynorketamine.
Magnetic solid-phase extraction combined with UPLC-MS/MS: A novel application for the analysis of alkylphenols and bisphenols in urine.
A Validated Quantitative LC-MS/MS Method for Determination of Deucravacitinib in Rat Plasma and Its Application to a Pharmacokinetic Study.
[Determination of nine markers of tobacco exposure in urine by supported liquid extraction-liquid chromatography-mass spectrometry].
A high-throughput LC-MS/MS method for simultaneous analysis of albendazole, albendazole sulfoxide and albendazole sulfone in human plasma.
LC-QTOF-MSE with MS1-based precursor ion quantification and SiMD-assisted identification enhances human urine metabolite analysis.
Coupling countercurrent chromatography to mass spectrometry to resolve natural products complex mixtures.
Rapid Annotation Strategy for in Vivo Phase II Metabolites of Anabolic-Androgenic Steroids Using Liquid Chromatography-Ion Mobility-Mass Spectrometry.
mineMS2: annotation of spectral libraries with exact fragmentation patterns.
Non-invasive assessment of free steroid hormones: development of a high-throughput LC-MS/MS method for salivary steroid hormone quantification.
LC-MS/MS quantification of nusinersen in rat cerebrospinal fluid and preclinical pharmacokinetics study application.
HSQC/F1-PSYCHE TOCSY NOAH Supersequence for High-Resolution NMR Analysis of Urine Metabolites.
Development of an LC-MS/MS assay to analyze a lipid-conjugated siRNA by solid phase extraction (SPE) in mouse plasma and tissue using a stable isotope labeled internal standard (SILIS).
Multilaboratory Untargeted Mass Spectrometry Metabolomics Collaboration to Identify Bottlenecks and Comprehensively Annotate A Single Dataset.
The first exploration of pseudo-protein-precipitation: High-throughput pretreatment for serum vitamin A/D/E/K analysis.
A Robust and Accurate Filter Paper-Based Dried Plasma Spot Method for Bictegravir Monitoring in HIV Therapy.
Repurposing proteomic nanoLC-MS platforms for untargeted metabolomics: evaluating DIA and polarity switching performance in human plasma.
Analytical development and application of a targeted liquid chromatography-tandem mass spectrometry assay for chimeric aducanumab.
Rapid and Simplified Determination of Amphetamine-Type Stimulants Using One-Pot Synthesized Magnetic Adsorbents with Built-In pH Regulation Coupled with Liquid Chromatography-Tandem Mass Spectrometry.
Development of an LC-MS/MS method for analysis of levamisole in poultry and livestock products.
High-Coverage Profiling of Hydroxyl and Amino Compounds in Sauce-Flavor Baijiu Using Bromine Isotope Labeling and Ultra-High Performance Liquid Chromatography-High-Resolution Mass Spectrometry.
Novel approach to urinary 11-nor-9-carboxy-delta-9-tetrahydrocannabinol analysis in forensic applications using disposable, graphene-based electrochemical sensor coupled with monolithic micro-solid-phase extraction.
Punc'data: A Versatile Tool for Molecular Formula Assignment, Interactive Visualization, and Comparison of Data from High-Resolution Mass Spectrometry of Complex Mixtures.

Biomed Chromatogr. 2025 Sep;39(9): e70171

Development and Validation of a Rapid LC-MS/MS Method for Plasma Analysis of Ketamine, Norketamine, Dehydronorketamine, and Hydroxynorketamine.

Jan Thomann, Selina Kraus, Livio Erne, Severin B Vogt, Matthias E Liechti, Dino Luethi.

  Ketamine, a well-established dissociative anesthetic, has recently gained significant attention for its rapid-acting antidepressant effects, particularly in treatment-resistant depression. In this study, we developed and validated a state-of-the-art liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the bioanalysis of ketamine and its metabolites, norketamine, dehydronorketamine (DHNK), and (2R,6R)-hydroxynorketamine (HNK), in human plasma. The method features a small sample volume, a streamlined protein precipitation protocol, and a rapid sample runtime. The mobile phase gradient is composed of an aqueous ammonium hydrogen carbonate solution and pure acetonitrile. Using positive electrospray ionization, linear quantification ranges of 1-1,000 ng/mL were established for ketamine and norketamine, while ranges of 0.25-100 ng/mL for DHNK and 2.5-1,000 ng/mL for (2R,6R)-HNK were achieved. The method demonstrated high accuracy, precision, selectivity, and sensitivity, along with consistent matrix effects, efficient extraction recovery, and analyte stability. Finally, the method was successfully applied to assess the pharmacokinetics of six clinical trial participants. Overall, this LC-MS/MS method offers a robust and efficient approach for the achiral quantification of ketamine and its metabolites in human plasma. Its minimal sample preparation and reduced analytical runtime make it particularly well-suited for clinical studies, drug monitoring, and forensic investigations.

Keywords:  bioanalysis; clinical study; liquid chromatography; mass spectrometry; pharmacokinetics

DOI:  https://doi.org/10.1002/bmc.70171
J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Jul 16. pii: S1570-0232(25)00294-6. [Epub ahead of print]1264 124740

Magnetic solid-phase extraction combined with UPLC-MS/MS: A novel application for the analysis of alkylphenols and bisphenols in urine.

Junlin Wang, Nianhua Zhang, Zhiyuan Wang, Peng Wang, Yiyao Cao.

  A rapid, sensitive, simple, and accurate method was developed for the simultaneous determination of 3 alkylphenols (APs) and 11 bisphenols (BPs) in urine based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Following enzymatic hydrolysis of urine samples, corresponding isotope internal standards were added. Magnetic solid-phase extraction (M-SPE) technology was employed for separation and enrichment of analytes, followed by UPLC-MS/MS analysis. Results showed that within the defined concentration ranges, calibration curves for both APs and BPs exhibited excellent linearity, with all correlation coefficients (r) >0.999. The method demonstrated excellent precision and accuracy, with intra- and inter-day coefficients of variation (CVs) < 4.4 % and 4.9 %, respectively, and recoveries ranging from 80.8 % to 107.7 %. Limits of detection (LODs) of the 14 target analytes were 0.006 ng/mL-0.6 ng/mL, and limits of quantification (LOQs) were 0.02 ng/mL-2.0 ng/mL. When applied to quantify APs and BPs in urine samples, the method proved effective, demonstrating rapidity, sensitivity, simplicity, and accuracy, thus making it highly suitable for detecting APs and BPs in urine.

Keywords:  Alkylphenols; Bisphenols; Magnetic solid-phase extraction; UPLC-MS/MS; Urine

DOI:  https://doi.org/10.1016/j.jchromb.2025.124740
Biomed Chromatogr. 2025 Sep;39(9): e70169

A Validated Quantitative LC-MS/MS Method for Determination of Deucravacitinib in Rat Plasma and Its Application to a Pharmacokinetic Study.

Pottabattula Mahesh, M Akiful Haque.

  We developed and validated a novel analytical methodology for the precise quantification of deucravacitinib, an oral TYK2 inhibitor for treating moderate-to-severe plaque psoriasis in adults. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in this method for sensitive detection of the compound in rat plasma. Analytical separation was performed utilizing an ACE C18 column (4.6 × 100 mm, 5-μm particle size) with a carefully optimized mobile phase composition of methanol and 2-mM ammonium formate (90:10, v/v), maintained at a consistent flow rate of 0.9 mL/min. Detection was executed in positive ionization mode, targeting multiple reaction monitoring (MRM) transitions of m/z 426.8 → 358.4 for the analyte and m/z 394.1 → 363.2 for the internal standard. The validation of the analytical method encompassed an assessment of selectivity, linearity, accuracy, precision, recovery, and stability. This method demonstrated stability, specificity, and no matrix effect at three concentration levels (1.606, 267.600, 507.780 ng/mL). The method's lower limit of quantification (LLOQ) is 0.556 ng/mL. The calibration curve demonstrates linearity from the LLOQ up to 668.132 ng/mL, exhibiting a high correlation coefficient (r2 = 0.9976). The intraday and interday precisions were less than 6.62% and 5.95%, respectively, with accuracies ranging from 90.68% to 103.80%. The recovery of deucravacitinib ranged from 95.34% to 103.80% and remained stable under different conditions. After successful validation, the method was used for pharmacokinetic profiling of deucravacitinib in rats following oral administration.

Keywords:  LC–MS/MS; deucravacitinib; method validation; pharmacokinetics; psoriasis; rat plasma

DOI:  https://doi.org/10.1002/bmc.70169
Wei Sheng Yan Jiu. 2025 Jul;54(4): 654-662

[Determination of nine markers of tobacco exposure in urine by supported liquid extraction-liquid chromatography-mass spectrometry].

Yongjie Yang, Guannian Liu, Yifu Lu, Changming Ding, Xiaoming Shi.

   OBJECTIVE: To establish a liquid chromatography-mass spectrometry method for the simultaneous determination of nine tobacco exposure biomarkers in human urine, including: nicotine, cotinine, trans-3'-hydroxycotinine, nicotine nitrogen oxide, cotinine nitrogen oxide, nornicotinine, norcotinine, anatabine, and anabasine.
METHODS: Urine samples were hydrolyzed by adding β-glucuronidase/arylsulfatase(1000 units/sample) and shaking at 37 ℃ overnight in the dark. Deuterium-labeled internal standards were added, and the samples were extracted using a 96-well supported liquid extraction plate. The plate was eluted with 1.8 mL of isopropanol-dichloromethane solution(5∶95, V/V) and dried under a stream of nitrogen. The residues were reconstituted in pure water for analysis. A Gemini® 3 μm NX-C18 110A(2.0 mm×150 mm, 1.9 μm) column was used for separation, with gradient elution using 0.1%(V/V) ammonia solution and methanol as the mobile phase. The method utilized liquid chromatography-tandem mass spectrometry(LC-MS/MS) with a heated electrospray ionization source, employing parallel reaction monitoring and positive ion mode scanning.
RESULTS: The method exhibited correlation coefficients(r) for the standard curves of the nine tobacco exposure markers ranging from 0.9984 to 0.9999. The detection limits were between 0.02 and 1.40 ng/mL, and the quantitation limits were between 0.06 and 4.60 ng/mL. The matrix effect ranged from 85.9% to 109%. The spiked recoveries ranged from 83.5% to 115%, and the relative standard deviations ranged from 1.0% to 16.3%(n=6).
CONCLUSION: This method is characterized by high sensitivity, precision, and accuracy, making it suitable for the determination of the nine tobacco exposure markers in the urine of both non-smoking and smoking individuals.

Keywords:  exposure marker; liquid chromatography-mass spectrometry; supported liquid extraction; tobacco; urine

DOI:  https://doi.org/10.19813/j.cnki.weishengyanjiu.2025.04.018
J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Jul 20. pii: S1570-0232(25)00295-8. [Epub ahead of print]1264 124741

A high-throughput LC-MS/MS method for simultaneous analysis of albendazole, albendazole sulfoxide and albendazole sulfone in human plasma.

Nela Žideková, Martin Kertys, Juraj Mokrý, Daniela Antolová, Katarína Šimeková, Róbert Rosoľanka.

  Albendazole is a benzimidazole derivative with a broad spectrum of antihelmintic activity. Its primary metabolite, albendazole sulfoxide, is responsible for the treatment's efficacy. On the other hand, it contributes to side effects and toxicity. Therefore, their quantification in plasma may increase therapeutic success and reduce associated risks by maintaining values within the therapeutic range. The present study introduces an LC-MS/MS method for the simultaneous quantification of albendazole, albendazole sulfoxide, and albendazole sulfone in human plasma. A simple and sensitive LC-MS/MS method was developed to monitor the plasma levels of albendazole (0.25-200 ng/mL), albendazole sulfoxide (5-3500 ng/mL), and albendazole sulfone (0.5-500 ng/mL) with a coefficient of variation below 7 %. A one-step extraction procedure using an Ostro™ plate was applied, and the extracts were analysed by gradient elution followed by detection on a mass spectrometer in multiple reaction monitoring mode. The method offers several significant advantages, including a low sample volume (50 μL), a short run time (4 min), and is sufficiently linear to quantify both low and high concentrations of all analytes. The method was successfully validated according to the ICH guideline M10 on bioanalytical method validation, covering selectivity, linearity of the calibration curve, lower limit of quantification (LLOQ), accuracy, precision, dilution integrity, carry-over effect, matrix effects, extraction recovery, and stability. The fully developed and validated method was used to determine albendazole, albendazole sulfoxide, and albendazole sulfone in the plasma samples of ten patients, illustrating the monitoring of albendazole treatment in patients with alveolar echinococcosis.

Keywords:  Albendazole; Albendazole sulfoxide; Alveolar echinococcosis; Liquid chromatography; Mass spectrometry; Metabolites; Therapeutic drug monitoring

DOI:  https://doi.org/10.1016/j.jchromb.2025.124741
Comput Struct Biotechnol J. 2025 ;27 3079-3089

LC-QTOF-MSE with MS1-based precursor ion quantification and SiMD-assisted identification enhances human urine metabolite analysis.

Alongkorn Kurilung, Suphitcha Limjiasahapong, Kwanjeera Wanichthanarak, Weerawan Manokasemsan, Khwanta Kaewnarin, Kassaporn Duangkumpha, Siriphan Manocheewa, Rossarin Tansawat, Roongruedee Chaiteerakij, Intawat Nookaew, Yongyut Sirivatanauksorn, Sakda Khoomrung.

  This study presents the development and validation of a liquid chromatography-quadrupole-time-of-flight mass spectrometry method with data-independent acquisition (LC-QTOF-MSE) for targeted quantification, post-targeted screening, and untargeted metabolite profiling. Using MS1-based precursor ion quantification, the method demonstrated excellent analytical performance with linearity (R² > 0.99), accuracy (84 %-131 %), and precision (1 %-17 % relative standard deviation (RSD)). Although LC-QTOF‑MSE sensitivity is at least nine-fold lower than LC-triple quadrupole MS with multiple reaction monitoring, it remains adequate for quantifying urinary metabolites, particularly those that fragment poorly or yield low‑intensity product ions. For post‑targeted screening and untargeted profiling, an in‑house reference library (the Siriraj Metabolomics Data Warehouse, SiMD), comprising 174 curated metabolite standards, was integrated into the workflow to enhance metabolite identification confidence. The official website for SiMD can be accessed at https://si-simd.com/. To demonstrate the method's utility, 11 amino and organic acids were quantified in urine samples from 100 healthy individuals. Four compounds-L-methionine, L-histidine, L-tryptophan, and trans-ferulic acid-were significantly higher levels in females (P < 0.05), likely reflecting sex-specific physiological or dietary intake differences. Post‑targeted screening identified 29 additional metabolites and assigned them to level 1 (m/z, RT, isotope pattern, and MS/MS spectra matched to reference standards) based on the Metabolomics Standards Initiative guidelines. Untargeted retrospective profiling revealed level 1 seven metabolites, including ribitol, creatine, glucuronic acid, trans-ferulic acid, succinic acid, dimethylglycine, and 3-hydroxyphenylacetic acid related to sex variation (VIP > 1.5). In summary, the LC-QTOF-MSE method coupled with SiMD provides a robust and comprehensive workflow for metabolomics analysis. It enables reliable target quantification and enhances confidence in metabolite identification while also reducing sample and instrumental demands. These features make it particularly well-suited for clinical metabolomics studies.

Keywords:  Data independent acquisition; Human urine; Mass spectrometry; Metabolomics; Post-targeted screening; Targeted quantification; Untargeted profiling

DOI:  https://doi.org/10.1016/j.csbj.2025.07.009
J Chromatogr A. 2025 Jul 14. pii: S0021-9673(25)00568-0. [Epub ahead of print]1758 466222

Coupling countercurrent chromatography to mass spectrometry to resolve natural products complex mixtures.

Felipe Costa Cardoso, Roberto Carlos Campos Martins, Ricardo Moreira Borges, Fernanda das Neves Costa.

  Countercurrent chromatography coupled with mass spectrometry (CCC-MS) has become a powerful tool for analysing complex natural product mixtures. This method provides high resolution, minimal sample loss, and versatility for both preparative and analytical applications. CCC, a liquid-liquid chromatography technique, excels in managing the inherent complexity of metabolomes, while MS offers sensitive detection and structural elucidation. The evolution of CCC-MS has faced early challenges, particularly regarding interfacing and ionisation efficiency. However, its development has propelled advancements such as reduced-pressure ionisation methods (e.g., ESI, APCI) and offline hyphenation strategies. Recent applications have demonstrated its effectiveness in metabolite profiling, isolating target compounds, and bio-guided fractionation, which contribute to the discovery of novel metabolites and their biological activities. Despite ongoing challenges in data analysis, improvements in data processing tools and molecular networking platforms are enhancing compound annotation and discovery. Overall, CCC-MS continues to be a critical asset in natural product research, providing valuable insights into the structural diversity of bioactive compounds.

Keywords:  Bio-guided fractionation; CCC-MS; Fingerprinting; Metabolite profiling; Metabolomics

DOI:  https://doi.org/10.1016/j.chroma.2025.466222
J Am Soc Mass Spectrom. 2025 Jul 23.

Rapid Annotation Strategy for in Vivo Phase II Metabolites of Anabolic-Androgenic Steroids Using Liquid Chromatography-Ion Mobility-Mass Spectrometry.

David C Koomen, Katrina L Leaptrot, Jody C May, Bailey S Rose, Kyle E Lira, Julia A Raziel, Andrew D Pumford, Gustavo de A Cavalcanti, Monica C Padilha, Henrique M G Pereira, John A McLean.

  Doping control laboratories are responsible for the precise measurement of anabolic-androgenic steroids (AASs) and determination of athlete usage. Intact phase II AASs are difficult to analyze due to their low abundance in complex biological matrices and their structural similarities that convolute tandem mass spectrometry interpretation. Discovery efforts of unknown phase II metabolites of new-to-the-field steroids have been challenging due to these deficiencies in current analytical techniques. Several methods for determining unknown conjugated AAS compounds have been developed that include deuterium tagging, fractionation, derivatization, and utilization of synthesized standards. Ion mobility (IM), a rapid gas-phase separation, allows for improved molecular differentiation and provides additional information for analyzing intact phase II AASs without sacrificing throughput. Here, candidate metabolites were putatively identified for oxymetholone (OXM) and methyl-1-testosterone (M1T) utilizing liquid chromatography-ion mobility-mass spectrometry (LC-IM-MS) and two independent data analysis strategies: a fully untargeted approach using mass defect analysis and collision cross section (CCS) filtering and a pseudotargeted approach using the biologically anticipated isotopic envelope in conjunction with CCS filtering, temporal profiling, and tandem mass spectrometry confirmation. A proof-of-concept time-course study was conducted using the urine from healthy male individuals after steroid administration. The fully untargeted approach reduced the number of original features by >85% while the pseudotargeted approach reduced original features by >99%, yielding 11 possible novel phase II AAS candidates for OXM and 23 for M1T.

Keywords:  CCS regression model; LC-IM-MS; mass−mobility correlation; nontargeted discovery workflow; phase II AAS; untargeted metabolomics

DOI:  https://doi.org/10.1021/jasms.5c00129
J Cheminform. 2025 Jul 24. 17(1): 111

mineMS2: annotation of spectral libraries with exact fragmentation patterns.

Alexis Delabrière, Coline Gianfrotta, Sylvain Dechaumet, Annelaure Damont, Thaïs Hautbergue, Pierrick Roger, Emilien L Jamin, Olivier Puel, Christophe Junot, François Fenaille, Etienne A Thévenot.

  Identification is a major challenge in metabolomics due to the large structural diversity of metabolites. Tandem mass spectrometry is a reference technology for studying the fragmentation of molecules and characterizing their structure. Recent instruments can fragment large amounts of compounds in a single acquisition. The search for similarities within a collection of MS/MS spectra is a powerful approach to facilitate the identification of new metabolites. We propose an innovative de novo strategy for searching for exact fragmentation patterns within collections of MS/MS spectra. This approach is based on (i) a new representation of spectra as graphs of m/z differences, and (ii) an efficient frequent-subgraph mining algorithm. We demonstrate both on a spectral database from standards and on acquisitions in biological matrices that these new fragmentation patterns capture similarities that are not extracted by existing methods, and facilitate the structural interpretation of molecular network components and the elucidation of unknown spectra. The mineMS2 software is publicly available as an R package ( https://github.com/odisce/mineMS2 ). SCIENTIFIC CONTRIBUTION: We present an innovative strategy for structural elucidation, which extracts exact fragmentation patterns of m/z differences within collections of MS/MS spectra. The algorithms are implemented in a software library enabling efficient mining of MS/MS data and coupling to molecular networks. We show on real datasets the specific value of the patterns as fragmentation graphs for structural interpretation and de novo identification, and their complementarity to existing approaches.

Keywords:  Computer-aided structure elucidation; Frequent subgraph mining; Graph theory; Mass spectrometry; Metabolomics

DOI:  https://doi.org/10.1186/s13321-025-01051-y
Anal Bioanal Chem. 2025 Jul 18.

Non-invasive assessment of free steroid hormones: development of a high-throughput LC-MS/MS method for salivary steroid hormone quantification.

Tove Slettvoll, Jeanette Wahlberg, Yvonne Lood, Martin Josefsson, Elisabeth Aardal, Samira Salihovic.

  Steroid hormone concentrations reflect diverse physiological and pathological processes and have been recognized as valuable biomarkers for disease, with growing interest in their potential for patient stratification in precision medicine. Salivary steroid concentrations should reflect the free (biologically active) steroids in circulation, as steroids in the bloodstream passively diffuse to saliva. This allows for the direct measurement of free steroids without transporter protein-bound hormones (inactive form). However, implementation of salivary steroid quantification in larger studies remains limited by challenges associated with sample preparation. We began by reviewing the literature on relevant sample preparation approaches and identified commonly used 96-well solid phase extraction (SPE) methods for further evaluation. Three sample preparation methods were selected and assessed in terms of internal standard recovery and matrix effects, and their response was also compared using electrospray (ESI) versus UniSpray ionization (USI) liquid chromatography-tandem mass spectrometry (LC-MS/MS). We demonstrate a sensitive and rapid high-throughput method with Oasis HLB µElution SPE of 200 μL saliva in 96-well format and USI-LC-MS/MS for major steroids (testosterone, androstenedione, cortisone, cortisol, and progesterone) in saliva. The method achieved optimal recovery (77%), matrix effects (33%), and sensitivity with detection limits (MDL) ranging between 1.1 and 3.0 pg/mL and linearity (r2 = 0.99). Intra-plate and inter-plate coefficient of variation (CV) was below 7% and 20% using USI. USI provided a higher (2.0-2.8-fold) response than ESI and higher signal-to-noise ratio (S/N). The method was then applied to 97 authentic saliva samples (41 male and 56 female) and significant correlations between age and BMI, and androgen levels were observed in both sexes. The proposed 96-well SPE USI-LC-MS/MS method is well-suited for determining steroid hormones in saliva with potential usefulness in large-scale studies and clinical settings.

Keywords:  Extraction; Free steroid hormones; LC–MS/MS; Saliva; Unispray ionization

DOI:  https://doi.org/10.1007/s00216-025-06005-9
Bioanalysis. 2025 Jul 21. 1-8

LC-MS/MS quantification of nusinersen in rat cerebrospinal fluid and preclinical pharmacokinetics study application.

Yujie Li, Shu Zhang, Xiayi Wang, Xiaochuan Li, Lizhong Guo.

   BACKGROUND: Background: An oligonucleotide drug named nusinersen sodium is used to treat Spinal Muscular Atrophy (SMA), requires accurate detection for therapeutic research. There are no published reports on liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for detecting nusinersen in rat cerebrospinal fluid (CSF).
METHODS: An LC-MS/MS method has been created and verified to detect nusinersen in Sprague-Dawley (SD) rat CSF. The method employed solid-phase extraction for post-extraction analysis and used dT20 as an internal standard. Negative ion multiple reaction monitoring (MRM) mode scanning and the electrospray ionization (ESI) source were used. The method was validated over a concentration range of 5-2000 ng/mL with a Lower Limit of Quantification (LLOQ) of for nusinersen at 5 ng/mL.
RESULTS AND CONCLUSIONS: The method achieves extremely high accuracy and precision, good linearity, high extraction recovery, and provides a useful approach for evaluating the pharmacokinetics of nusinersen in rats.

Keywords:  Antisense oligonucleotide drugs; HPLC-MS/MS; cerebrospinal fluid; nusinersen; pharmacokinetics; solid phase extraction

DOI:  https://doi.org/10.1080/17576180.2025.2535949
Magn Reson Chem. 2025 Jul 20.

HSQC/F1-PSYCHE TOCSY NOAH Supersequence for High-Resolution NMR Analysis of Urine Metabolites.

Aditi Pandey, Nidhi Tiwari, Amrita Sahu, Bikash Baishya.

  Accurate assignment of metabolites is the backbone of metabolomics studies. Two-dimensional (2D) NMR plays a critical role in the accurate assignment of metabolites. Characterization of 2D spectra such as 1H-13C HSQC and 1H-1H TOCSY combined with database queries enables reliable metabolite identification for metabolic profiling and biological interpretation. However, recording a high-quality 1H-13C HSQC spectrum at 13C natural abundance in biofluids requires extensive NMR signal averaging, often taking up to 24 h. Reducing the number of t1 increments or scans is not useful in metabolomics as it compromises the sensitivity needed to detect low-abundance metabolites. "NMR by Ordered Acquisition using 1H detection," or NOAH, supersequences are ideally suited for accelerated data collection in biofluids. Instead of shortening individual experiments, NOAH enables the simultaneous acquisition of multiple 2D experiments without compromising sensitivity. The principle of NOAH lies in utilizing the undisturbed magnetization from one experiment (e.g., 1H-13C HSQC) for subsequent experiments (e.g., 1H-1H TOCSY) within the same scan. Previous studies have demonstrated the utility of the HSQC + TOCSY NOAH-2 supersequence for metabolomics applications. Nevertheless, due to the complexity of biofluids, even regular 2D TOCSY spectra often suffer from signal overlap, arising from numerous metabolite peaks, multiplet structures, and limited 1H chemical shift dispersion. The pure shift F1-PSYCHE TOCSY experiment addresses this challenge by offering a single peak per resonance, thereby greatly reducing signal overlap. In this work, we present HSQC + F1-PSYCHE TOCSY NOAH-2 supersequence for the analysis of human urine.

Keywords:  F1‐PSYCHE‐TOCSY; NOAH; chirp pulse; excitation sculpting; metabolomics; zero quantum filter

DOI:  https://doi.org/10.1002/mrc.70013
Bioanalysis. 2025 Jul 24. 1-11

Development of an LC-MS/MS assay to analyze a lipid-conjugated siRNA by solid phase extraction (SPE) in mouse plasma and tissue using a stable isotope labeled internal standard (SILIS).

Ethan J Sanford, Jianzhong Chen, Julia Tran, Ilia Korboukh, Guangnong Zhang.

   BACKGROUND: Oligonucleotide therapeutics (ONTs) are a rapidly growing class of drug, with 20+ approved drugs on the market and more undergoing preclinical and clinical investigation for various indications. Many groups in the field are appending chemical modifications to modulate tissue specificity. Conjugation of long-chain fatty acids to siRNA molecules increases the hydrophobicity of the analyte and poses analytical challenges for extraction and LC-MS.
RESULTS: We report the development and optimization of an SPE extraction method for a lipid-conjugated siRNA. To improve assay quantitation by LC-MS, a stable isotope label internal standard (SILIS) was evaluated that enabled robust quantitation with high accuracy and precision (±5% in most cases).
CONCLUSION: We demonstrate the performance of the assay in mouse plasma and tissue homogenates and apply the assay to the determination of tissue exposure and plasma PK profile for a novel lipid-conjugated siRNA molecule and suggest that a SILIS quantitation approach should be standard practice in siRNA bioanalysis.

Keywords:  Bioanalysis; LC-MS/MS; SILIS; method development; oligonucleotide; siRNA; solid phase extraction; stable isotope label

DOI:  https://doi.org/10.1080/17576180.2025.2535953
Anal Chem. 2025 Jul 22.

Multilaboratory Untargeted Mass Spectrometry Metabolomics Collaboration to Identify Bottlenecks and Comprehensively Annotate A Single Dataset.

Joelle Houriet, Preston K Manwill, Armando Alcázar Magaña, Victoria M Anderson, Mehdi A Beniddir, Samuel Bertrand, Jaewoo Choi, Trevor N Clark, Leonard J Foster, Maria Halabalaki, Alan K Jarmusch, Niek F de Jonge, Aswad Khadilkar, John B MacMillan, Claudia S Maier, Luke C Marney, Guillaume Marti, Eleni V Mikropoulou, Damien Olivier-Jimenez, Amélie Perez, Justin J J van der Hooft, Mitja M Zdouc, Roger G Linington, Nadja B Cech.

Annotation is the process of assigning features in mass spectrometry metabolomics data sets to putative chemical structures or "analytes." The purpose of this study was to identify challenges in the annotation of untargeted mass spectrometry metabolomics datasets and suggest strategies to overcome them. Toward this goal, we analyzed an extract of the plant ashwagandha (Withania somnifera) using liquid chromatography-mass spectrometry on two different platforms (an Orbitrap and Q-ToF) with various acquisition modes. The resulting 12 datasets were shared with ten teams that had established expertise in metabolomics data interpretation. Each team annotated at least one positive ion dataset using their own approaches. Eight teams selected the positive ion mode data-dependent acquisition (DDA) data collected on the Orbitrap platform, so the results reported for that dataset were chosen for an in-depth comparison. We compiled and cross-checked the annotations of this dataset from each laboratory to arrive at a "consensus annotation," which included 142 putative analytes, of which 13 were confirmed by comparison with standards. Each team only reported a subset (24 to 57%) of the analytes in the consensus list. Correct assignment of ion species (clusters and fragments) in MS spectra was a major bottleneck. In many cases, in-source redundant features were mistakenly considered to be independent analytes, causing annotation errors and resulting in overestimation of sample complexity. Our results suggest that better tools/approaches are needed to effectively assign feature identity, group related mass features, and query published spectral and taxonomic data when assigning putative analyte structures.

DOI: https://doi.org/10.1021/acs.analchem.4c05577
Anal Chim Acta. 2025 Oct 01. pii: S0003-2670(25)00731-7. [Epub ahead of print]1369 344337

The first exploration of pseudo-protein-precipitation: High-throughput pretreatment for serum vitamin A/D/E/K analysis.

Shao-Ting Wang, Ze-Gang Wu, Cheng Liu.

   BACKGROUND: The accurate quantification of fat-soluble vitamins (A, D, E, K) in serum is essential for clinical diagnostics. However, traditional methods involving protein precipitation (PP) workflows, which require vortex mixing and centrifugation, pose significant challenges for automation. Current automated platforms are often complex, costly, and limited in throughput. This study presents an innovative strategy called "Pseudo-Protein-Precipitation combined with Cold-Induced Phase Separation (PPP + CIPS)" to streamline pretreatment and improve high-throughput compatibility.
RESULTS: The PPP + CIPS approach utilizes alkalized acetonitrile to form a semi-homogeneous serum suspension, facilitating in-situ vitamin extraction through CIPS. Eliminating vortexing and centrifugation for the very first time, this new method can be efficiently executed using 96-well plates and multi-channel pipettes. The whole protocol significantly reduced pretreatment time to approximately one-third of that required by PP. Validation results indicated excellent linearity, accuracy (86.5-113.2 %), precision (CV <10.5 %), and minimal matrix effects (88.8-112.7 %). Clinical comparisons (n = 384) demonstrated strong agreement with certified methods, with 94 % of retinol, 93 % of 25OHD3, 91 % of α-tocopherol, and 89 % of K1 falling within ±20 % limits.
SIGNIFICANCE: The PPP + CIPS strategy represents a transformative advancement for high-throughput clinical testing. Its compatibility with 96-well formats and static workflows positions it as a foundational element for next-generation automated LC-MS/MS platforms, effectively addressing current bottlenecks in clinical mass spectrometry.

Keywords:  25-Hydroxyvitamin D; Cold-induced phase separation (CIPS); Fat-soluble vitamins; LC-MS/MS; Phylloquinone; Retinol; α-tocopherol

DOI:  https://doi.org/10.1016/j.aca.2025.344337
Rapid Commun Mass Spectrom. 2025 Nov 15. 39(21): e10110

A Robust and Accurate Filter Paper-Based Dried Plasma Spot Method for Bictegravir Monitoring in HIV Therapy.

Arpita Sathyanarayanan, Roopashri N Arekal, Divyashree Somashekara.

   CONTEXT: Therapeutic drug monitoring (TDM) involves the collection of biological samples such as blood, plasma, urine, and saliva. The most commonly used biological matrix for the detection of drugs is either blood or plasma, as they are widely accepted by the regulatory authorities. Such studies require a significant amount of blood to be collected and even more if the study is performed in a plasma sample. The growing demand to minimize the blood or biological samples required for the study of drugs, dried blood spot, or the dried plasma spot techniques has been studied by its demand.
OBJECTIVE: The main aim was the development of a novel method for the determination of the circulating blood plasma levels in clinical samples using spotted and dried plasma on filter paper as a substrate detection of bictegravir, an HIV integrase strand transfer inhibitor (INSTI) drug from dried plasma spots.
MATERIALS AND METHODS: The quantitation, as well as the detection of the plasma drug concentration, was done using liquid chromatography-tandem mass spectrometry LC-MS/MS. Sixty microliters of plasma spiked with 2% of the drug was spotted on Whatman filter paper and was left to dry at room temperature. The drug was extracted using methanol as a precipitating agent.
RESULTS: The extraction technique yielded a recovery of 100%. The assay exhibited excellent linearity in the range of 20-1200 ng/mL.
DISCUSSION AND CONCLUSION: The method developed is a robust, simple, and accurate method to extract drug from the plasma. This method enables to produce a clean sample, proving to be cheaper and more accurate with maximum recovery.

Keywords:  bictegravir; chromatography; dried plasma spot (DPS); therapeutic drug monitoring (TDM)

DOI:  https://doi.org/10.1002/rcm.10110
Expert Rev Proteomics. 2025 Jul 24. 1-8

Repurposing proteomic nanoLC-MS platforms for untargeted metabolomics: evaluating DIA and polarity switching performance in human plasma.

Frederico G Pinto, Alexander D Giddey, Nesrin Mohamed, Rauda S B Almarri, Munazza Murtaza, Nasna Nassir, Omer S Alkhnbashi, Mohammed J Uddin, Nelson C Soares.

   BACKGROUND: Many of the advanced MS methods applied in proteomics such as nanoflow LC-MS with data-independent acquisition have yet to be verified and/or optimized on metabolomics applications.
RESEARCH DESIGN AND METHODS: This study evaluates the feasibility of repurposing a proteomics-optimized nanoLC-MS platform for untargeted metabolomics. Using NIST SRM 1950 reference human plasma, we compared the performance of polarity switching and separate polarity modes under DIA conditions, focusing on metabolite coverage, annotation, and response linearity.
RESULTS: We observed, in the separate polarity and switching polarity runs 669 and 353 features in (+) mode and 558 and 446 features in (-) mode, respectively. A total of 233 metabolites were annotated using the (±) separate polarities and 179 using the (±) switching polarity based on MassBank of North America (MoNA) public MS library and filtered with the Human Metabolome Database (HMDB). Both switching and separate polarity methods performed well regarding response linearities which were investigated by spiking some amino acid compounds into plasma matrix.
CONCLUSIONS: The polarity switching DIA approach for metabolomics reduced sample consumption and analysis time, but led to fewer detected features and annotations compared to separate polarity runs. These findings support the use of unified nanoLC-MS platforms for integrated multi-omics analysis.

Keywords:  Untargeted metabolomics; data independent analysis; human plasma; mass spectrometry; switching polarity

DOI:  https://doi.org/10.1080/14789450.2025.2537210
MAbs. 2025 Dec;17(1): 2537118

Analytical development and application of a targeted liquid chromatography-tandem mass spectrometry assay for chimeric aducanumab.

Emma H Doud, Kasi Hansen, Kathryn A Haynes, Kierra Eldridge, Jaison Arrivalagan, Nitin Charbe, Lais Da Silva, Sara K Quinney, Amber L Mosley, Stacey J Sukoff Rizzo, Paul R Territo.

  A sensitive and specific liquid chromatography-tandem mass spectrometry assay was developed for the quantification of chimeric aducanumab (chAdu), a therapeutic antibody targeting pathological amyloid plaques in Alzheimer's disease, in murine biological matrices. This method addresses the challenges of quantifying biotherapeutics in multiple tissue types within preclinical animal models with complex genetic backgrounds, where traditional enzyme-linked immunosorbent assay (ELISA) methods may suffer from interference and limited sensitivity. The assay uses parallel reaction monitoring on a Lumos Tribrid Orbitrap mass spectrometer, coupled with an Evosep LC system, and AssayMap Bravo-based automated sample processing. Key features include protein A enrichment for improved sensitivity, optimized peptide selection based on sequence uniqueness and ionization response, and incorporation of stable isotope-labeled peptides for accurate quantification. Assay performance was evaluated for selectivity, repeatability, and stability. The fit-for-purpose assay was successfully applied to quantify chAdu in both mouse cortex and plasma samples obtained from a pilot pharmacokinetic study of a mouse model of amyloid plaque deposition. This targeted mass spectrometry workflow offers a robust and reproducible alternative to ELISA for preclinical biotherapeutic analysis, particularly when dealing with complex biological samples.

Keywords:  5XFAD; Aducanumab; PRM; biotherapeutic; pharmacokinetics; targeted mass spectrometry

DOI:  https://doi.org/10.1080/19420862.2025.2537118
J Xenobiot. 2025 Jul 02. pii: 102. [Epub ahead of print]15(4):

Rapid and Simplified Determination of Amphetamine-Type Stimulants Using One-Pot Synthesized Magnetic Adsorbents with Built-In pH Regulation Coupled with Liquid Chromatography-Tandem Mass Spectrometry.

Yabing Shan, Ying Chen, Jiayi Li, Xianbin Zeng, Rui Jia, Yuwei Liu, Dongmei Li, Di Chen.

   BACKGROUND: Amphetamine-type stimulants (ATS) in water pose significant public health and ecological risks, necessitating reliable and efficient detection methods. Current approaches often involve time-consuming pH adjustments and post-processing steps, limiting their practicality for high-throughput analysis. This study aimed to develop a streamlined method integrating pH regulation and adsorption into a single material to simplify sample preparation and enhance analytical efficiency.
METHODS: A novel Fe3O4/MWCNTs-OH/CaO composite adsorbent was synthesized via a one-pot grinding method, embedding pH adjustment and adsorption functionalities within a single material. This innovation enabled magnetic solid-phase extraction (MSPE) without pre-adjusting sample pH or post-desorption steps. The method was coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for ATS detection. Optimization included evaluating adsorption/desorption conditions and validating performance in real water matrices.
RESULTS: The method demonstrated exceptional linearity (R2 > 0.98), low detection limits (0.020-0.060 ng/mL), and high accuracy with relative recoveries of 92.8-104.8%. Precision was robust, with intra-/inter-day relative standard deviations (RSDs) below 11.6%. Single-blind experiments confirmed practical applicability, yielding consistent recoveries (relative errors: 1-8%) for ATS-spiked samples at 0.8 and 8 ng/mL. Compared to existing techniques, the approach reduced processing time to ~5 min by eliminating external pH adjustments and post-concentration steps.
CONCLUSIONS: This work presents a rapid, reliable, and user-friendly method for ATS detection in complex environmental matrices. The integration of pH regulation and adsorption into a single adsorbent significantly simplifies workflows while maintaining high sensitivity and precision. The technique holds promise for large-scale environmental monitoring and forensic toxicology, offering a practical solution for high-throughput analysis of emerging contaminants.

Keywords:  amphetamine-type stimulants (ATSs); built-in pH regulation; liquid chromatography–tandem mass spectrometry (LC-MS/MS); magnetic adsorbent; magnetic solid-phase extraction (MSPE); one-pot grinding

DOI:  https://doi.org/10.3390/jox15040102
J AOAC Int. 2025 Jul 22. pii: qsaf068. [Epub ahead of print]

Development of an LC-MS/MS method for analysis of levamisole in poultry and livestock products.

Ya-Chun Chou, Pei-Jie Zheng, Chih-Neng Huang, Shu-Han Chang, Ya-Min Kao, Mei-Chih Lin, Lih-Ching Chiueh, Su-Hsiang Tseng.

BACKGROUND: Levamisole is an imidazothiazole anthelmintic agent widely used in poultry and livestock. In Taiwan, the Ministry of Health and Welfare has established MRLs ranging from 0.01 to 1 μg/g for eggs, milk, and various livestock and poultry tissues.
OBJECTIVE: To support regulatory monitoring, a chiral LC-MS/MS method with simple sample preparation was developed for determining levamisole residues in chicken muscle, porcine muscle, liver, kidney, fat, poultry eggs, and milk from food-producing animals.
METHOD: Separation of levamisole and its enantiomer dexamisole was achieved using an Astec Cyclobond I 2000 DMP column with 100 mM ammonium acetate and acetonitrile as the mobile phase. The sample was extracted with acetonitrile/methanol (95:5, v/v) containing 1% formic acid, followed by clean-up with acetonitrile-saturated n-hexane.
RESULTS: The method demonstrated good linearity (r > 0.995, 0.5-25 ng/mL) for three quantitative methods in all tested matrices. The method achieved a LOQ of 0.005 μg/g in all matrices. While the pre-spiked tissue calibration curve provided higher recoveries (96.3%-110.1%) by compensating for both matrix effects and analyte losses during extraction, it was more labor-intensive. In contrast, the matrix-matched calibration curve and ISTD-normalized solvent calibration curve offered slightly lower recoveries (84.8%-100.4%) but showed greater practicality for routine monitoring. All calibration strategies met the accuracy and precision criteria specified in European Commission Decision 2002/657/EC and the TFDA validation guidelines. Furthermore, levamisole residues were not detected in any of the 10 commercial livestock and poultry products analyzed, confirming the applicability of the method for food surveillance.
CONCLUSIONS: A simple and rapid LC-MS/MS method was developed for the determination of levamisole in poultry and livestock matrices, demonstrating satisfactory sensitivity, accuracy, and selectivity. The method is suitable for routine monitoring and large-scale surveillance of levamisole residues in food products.
HIGHLIGHTS: Development and validation of an LC-MS/MS method involving simple solvent extraction for chiral determination of levamisole in livestock and poultry products with satisfactory sensitivity, accuracy, and selectivity.

DOI: https://doi.org/10.1093/jaoacint/qsaf068
Metabolites. 2025 Jul 09. pii: 464. [Epub ahead of print]15(7):

High-Coverage Profiling of Hydroxyl and Amino Compounds in Sauce-Flavor Baijiu Using Bromine Isotope Labeling and Ultra-High Performance Liquid Chromatography-High-Resolution Mass Spectrometry.

Zixuan Wang, Youlan Sun, Tiantian Chen, Lili Jiang, Yuhao Shang, Xiaolong You, Feng Hu, Di Yu, Xinyu Liu, Bo Wan, Chunxiu Hu, Guowang Xu.

  Background: Hydroxyl and amino compounds play a significant role in defining the flavor and quality of sauce-flavor Baijiu, yet their comprehensive analysis remains challenging due to limitations in detection sensitivity. In this study, we developed a novel bromine isotope labeling approach combined with ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) to achieve high-coverage profiling of these compounds in sauce-flavor Baijiu. Methods: The method employs 5-bromonicotinoyl chloride (BrNC) for rapid (30 s) and mild (room temperature) labeling of hydroxyl and amino functional groups, utilizing bromine's natural isotopic pattern (Δm/z = 1.998 Da) for efficient screening. Annotation was performed hierarchically at five confidence levels by integrating retention time, accurate mass, and MS/MS spectra. Results: A total of 309 hydroxyl and amino compounds, including flavor substances (e.g., tyrosol and phenethyl alcohol) and bioactive compounds (e.g., 3-phenyllactic acid), were identified in sauce-flavor Baijiu. The method exhibited excellent analytical performance, with wide linearity (1-4 orders of magnitude), precision (RSD < 18.3%), and stability (RSD < 15% over 48 h). When applied to sauce-flavor Baijiu samples of different grades, distinct compositional patterns were observed: premium-grade products showed greater metabolite diversity and higher contents of bioactive compounds, whereas lower-grade samples exhibited elevated concentrations of acidic flavor compounds. Conclusions: These results demonstrate that the established method is efficient for the comprehensive analysis of hydroxyl and amino compounds in complex food matrices. The findings provide valuable insights for quality control and flavor modulation in sauce-flavor Baijiu production.

Keywords:  UHPLC-HRMS; bromine isotope labeling; chemical derivatization; food metabolomics; hydroxyl and amino compounds; sauce-flavor Baijiu

DOI:  https://doi.org/10.3390/metabo15070464
Anal Chim Acta. 2025 Oct 01. pii: S0003-2670(25)00753-6. [Epub ahead of print]1369 344359

Novel approach to urinary 11-nor-9-carboxy-delta-9-tetrahydrocannabinol analysis in forensic applications using disposable, graphene-based electrochemical sensor coupled with monolithic micro-solid-phase extraction.

Kesara Ar-Sanork, Wichayaporn Kamsong, Rawisara Woensanthia, Jeerakit Thangphatthanarungruang, Zhengjin Jiang, Theerin Sinchai, Chanpen Karuwan, Patcharin Chaisuwan.

   BACKGROUND: The escalating global use of cannabis as a narcotic demands the development of a rapid, cost-effective, and portable method for assessing cannabis intake in forensic contexts. A major cannabis metabolite, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), is commonly targeted for cannabis drug testing. However, the quantification of urinary THC-COOH typically relies on chromatographic methods, which require bulky, expensive instruments and skilled expertise. This study presents a novel approach for the simple, selective, and sensitive detection of THC-COOH in human urine samples by integrating monolithic pipette-tip solid-phase extraction (monolithic PT-SPE) with an electrochemical sensor based on disposable screen-printed graphene electrodes (SPGEs).
RESULTS: A C18-functionalised monolithic backbone, poly(stearyl methacrylate-co-ethylene dimethacrylate), is in situ synthesised within micro-pipette tips for effective urine sample cleanup and pre-concentration of THC-COOH before quantification using the SPGE-based sensor in a few minutes. Critical parameters for PT-SPE and electrochemical detection are systematically optimised. The method exhibits a wide linear range of 50-1000 ng mL-1 (R2 = 0.9980), with both a low limit of detection (5.2 ng mL-1) and a low limit of quantification (17.5 ng mL-1). Under optimal conditions, THC-COOH is effectively isolated from complex urine matrices, achieving a 14-fold signal enhancement and good recovery (80 %-110 %), with intra- and inter-day precisions of 5.9 % and 7.1 %, respectively. Both for authentic urine specimens and spiked samples, analysis results obtained using the method developed demonstrate strong correlation with liquid chromatography with tandem mass spectrometry (LC-MS/MS) results.
SIGNIFICANCE: We successfully employed an electrochemical sensor for the determination of THC-COOH in human urine specimens for the first time. By coupling it with the developed monolithic PT-SPE, we achieved direct detection of THC-COOH without requiring additional electrode surface modifications. The method is environmentally friendly, requiring only a minimal volume of reagents for both extraction and detection. Furthermore, it is efficient, simple and cost-effective.

Keywords:  11-Nor-9-carboxy-Δ(9)-tetrahydrocannabinol; Illicit drug; Micro-solid-phase extraction; Monolith; Screen-printed graphene electrode; Urine analysis

DOI:  https://doi.org/10.1016/j.aca.2025.344359
J Am Soc Mass Spectrom. 2025 Jul 24.

Punc'data: A Versatile Tool for Molecular Formula Assignment, Interactive Visualization, and Comparison of Data from High-Resolution Mass Spectrometry of Complex Mixtures.

Théo Voellinger, Sébastien Schramm, Pierre Pacholski, Nathan Traullé, Frédéric Aubriet.

The increasing use of ultrahigh-resolution mass spectrometry to investigate complex organic mixtures by nontargeted analysis using mainly direct infusion requires developing specialized software tools and algorithms to aid in and accelerate calibration, data processing, and analysis. To address this need, Punc'data, a JavaScript tool usable on a webpage for mass spectrometry (MS) data attribution, visualization, and comparison, was developed. Molecular formula attribution is performed using a network approach, where mass differences can be defined by the user or de novo determined by the software. Following the attribution process, the results obtained are visualized using charts commonly employed to study complex organic mixtures such as class histograms, van Krevelen diagrams, and Kendrick maps. Alternatively, data processed by other software programs can be imported for graphical representation. Emphasis has been placed on an interactive chart system designed to identify trends of chemical significance within, unique or common to different data sets. The comparison of different data sets is facilitated through principal component analysis.

DOI: https://doi.org/10.1021/jasms.5c00151