Journal of Mass Spectrometry最新文献

{"title":"Evaluation of the Chemical Profile by Paper Spray Mass Spectrometry of Eugenia uniflora Pulp, Peel, Seeds, and Jelly","authors":"Viviane D. M. Silva,&nbsp;Laiza A. Nogueira,&nbsp;Ana Luiza C. C. Ramos,&nbsp;Bruna V. Nunes,&nbsp;Claudio A. Lopes,&nbsp;Mauro R. Silva,&nbsp;Eric M. Garcia,&nbsp;Hosane Aparecida Taroco,&nbsp;Ricardo Manuel S. de Boavida Ferreira,&nbsp;Rodinei Augusti,&nbsp;Julio Onesio-Ferreira Melo","doi":"10.1002/jms.5173","DOIUrl":"10.1002/jms.5173","url":null,"abstract":"<p>Pitangueira (<i>Eugenia uniflora</i>) is a fruit tree found in the Cerrado, Caatinga, and Atlantic Forest Brazilian biomes. Due to its intense and characteristic aroma and flavor, its fruits (Brazilian cherry) can be consumed raw and as an ingredient in jellies, giving it better use and a more excellent shelf life. The objective of this work was to evaluate the chemical profile of chemical compounds in the pulp, peel, seed, and jelly prepared with the pulp and peel of Brazilian cherry. The characterization of the chemical profile was performed by a fast and simple method: paper spray ionization method coupled with mass spectrometry in positive and negative ionization modes. Forty-six compounds were tentatively identified in the negative mode and 15 in the positive mode, belonging to the classes of phenolic acids, organic acids, fatty acids, hydroxycinnamic acids, sugars, betalains, carotenoids, flavonoids, and tannins. Characterizing these native Brazilian fruits and their products may increase interest in their use, highlighting the potential of Brazilian cherry as a source of nutrients and bioactive compounds. Therefore, developing technological processes for better use and conservation of fruits and, at the same time, identifying the phytochemical compounds present in the product is a way of valuing and preserving our Brazilian biodiversity.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative UHPLC–MS/MS Analysis of Gemcitabine and Its Active and Inactive Metabolites in Pig Plasma and Lung Tissue in Preparation of Locoregional Therapies for Non–Small Cell Lung Cancer","authors":"Erik Claes,&nbsp;Jeroen M. H. Hendriks,&nbsp;Thérèse S. Lapperre,&nbsp;Johan Van Daele,&nbsp;Andreia Alves,&nbsp;Pieter Annaert,&nbsp;Stijn E. Verleden","doi":"10.1002/jms.5174","DOIUrl":"10.1002/jms.5174","url":null,"abstract":"<div>\u0000 \u0000 <p>Gemcitabine (dFdC), an effective chemotherapeutic for non–small cell lung cancer (NSCLC), acts through its active metabolite, dFdCTP. Its current pharmacokinetics (PK) knowledge is based on intravenous infusion, which does not represent locoregional administration. In contrast, locoregional studies focus on dFdC, neglecting the role of dFdU (inactive) and dFdCTP, limiting our lung-specific PK insights. Existing dFdCTP assays require lengthy runs and complex protocols, reducing their translatability for large-scale studies. This study presents an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) method to quantify dFdC, dFdU, and dFdCTP in pig lung tissue and plasma, improving gemcitabine's PK assessment following both systemic and locoregional therapies. A high-throughput UHPLC–MS/MS method was developed and validated for the quantification of dFdC, dFdU, and dFdCTP in pig plasma and lung tissue. Protein precipitation was used, followed by chromatographic separation on a Luna Omega Polar C18 column with a 4-min run time. Linearity was established over the ranges: 0.5–400.0 μg/mL (plasma) and 0.5–400.0 μg/g (lung tissue). It demonstrated robust accuracy, precision, and selectivity with minimal carryover and negligible matrix effects. Stability was confirmed for 4 h at 4°C, 40°C, and on the autosampler. The method's applicability was verified in study samples treated with a 30-min intravenous gemcitabine (1.25 g/m²) infusion. This UHPLC–MS/MS assay overcomes previous methodological limitations by reducing run time and simplifying sample preparation. Its robustness to quantify dFdC, dFdU, and dFdCTP in pig plasma and lung tissue has been confirmed, providing a valuable tool for future PK studies with locoregional therapies for NSCLC.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimizing Ionic Interference: An APCI-MS Strategy for Real-Time Reaction Monitoring in Ionic Liquids","authors":"Chiara Salvitti,&nbsp;Alessia Di Noi,&nbsp;Francesca Cosentino,&nbsp;Cinzia Michenzi,&nbsp;Federico Pepi,&nbsp;Marta Managò,&nbsp;Isabella Chiarotto,&nbsp;Anna Troiani","doi":"10.1002/jms.5176","DOIUrl":"10.1002/jms.5176","url":null,"abstract":"<div>\u0000 \u0000 <p>Ionic liquids (ILs) are a class of organic salts with melting points below 100°C. Owing to their unique chemical and physical properties, they are used as solvents and catalysts in various chemical transformations, progressively replacing common volatile organic solvents (VOCs) in green synthetic applications. However, their intrinsic ionic nature can restrict the use of mass spectrometric techniques to monitor the time progress of a reaction occurring in an IL medium, thus preventing one from following the formation of the reaction products or intercepting the reaction intermediates. The intense ionic signals related to the IL cation, anion, and their aggregates can indeed suppress the ionic intensities of substrates that are not intrinsically charged and often poorly ionizable. In this paper, we developed an atmospheric pressure chemical ionization mass spectrometry (APCI-MS) approach to overcome this limitation and minimize interference from the IL. The possibility of obtaining an estimation of the product yields by directly sampling the reaction mixture without quenching the process was tested by constructing calibration curves on three different model reactions, namely, (i) Knoevenagel condensation, (ii) oxidative esterification of aromatic aldehydes, and (iii) benzoin addition. A good correlation was obtained between the product yields measured by the APCI-MS procedure and those extrapolated from the isolated products. These results highlight the potential of this approach for real-time monitoring of reactions in ILs, eliminating the need for time-consuming extraction steps and minimizing the risk of losing critical mechanistic information.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Sensitive and Comprehensive LC-MS/MS Method for the Analysis of Hallucinogens, Synthetic Cathinones, and Synthetic Cannabinoids in Urine Samples","authors":"Bruno Pereira dos Santos,&nbsp;Letícia Birk,&nbsp;Vítor Camargo Pôrto,&nbsp;Sabrina Nunes Nascimento,&nbsp;Viviane Cristina Sebben,&nbsp;Sarah Eller,&nbsp;Tiago Franco de Oliveira","doi":"10.1002/jms.5178","DOIUrl":"10.1002/jms.5178","url":null,"abstract":"<p>The laboratory analysis of new psychoactive substances and related drugs is crucial for accurate clinical and forensic diagnosis of poisonings. Given this, a new LC-MS/MS method for analyzing hallucinogens, synthetic cathinones, and synthetic cannabinoids in urine was developed. Urine samples were extracted using a liquid–liquid extraction protocol optimized via a multivariate experimental design. An aliquot of 400 μL of urine was enzymatically hydrolyzed with β-glucuronidase and extracted with 700 μL of ethyl acetate. The resulting extracts were analyzed using LC-MS/MS, with a total chromatographic run time of 8 min. The method was validated according to the ANSI/ASB Standard 036 guideline and was applied to 24 samples from suspected poisoning cases. The lower limits of quantification ranged from 0.1 to 1 ng/mL. Within-run and between-run precision (CV) were &lt; 16%, and bias ranged from −12.8% to 19.8%. Nine of the 20 analytes investigated showed significant ionization suppression or enhancement (&gt; 25%). Only two analytes (2C-E and 2-oxo-3-OH-LSD) had a recovery rate lower than 70%. Among the 24 analyzed urine samples, one tested positive for 25B-NBOH, one for LSD, and two for 2-oxo-3-OH-LSD. The developed method enables the simultaneous quantification of 20 illicit drugs, serving as an efficient diagnostic tool for clinical and forensic laboratories.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the Unimolecular Breakdown Products of Short Deprotonated Per- and Poly-Fluorinated Acids and Alcohols","authors":"Angela S. Radnoff,&nbsp;Samuel Charpentier-St-Pierre,&nbsp;Paul M. Mayer","doi":"10.1002/jms.5175","DOIUrl":"10.1002/jms.5175","url":null,"abstract":"<p>The strong C–F bond found in per- and poly-fluorinated alkyl substances (PFAS) makes them resistant to degradation and thus persistent in the environment. One of the most common methods for quantifying PFAS in environmental matrices is to use tandem mass spectrometry. However, the dissociation of ions made by deprotonating PFAS alcohols and acids has only been qualitatively explored. In this study, we investigated the breakdown of deprotonated 2,2,3,3,3-pentafluoropropionic acid (<b>1</b>, m/z 163), 3,3,3-trifluoropropionic acid (<b>2</b>, m/z 127), 2,2,3,3,3-pentafluoro-1-propanol (<b>3</b>, m/z 149), 3,3,3-trifluoro-1-propanol (<b>4</b>, m/z 113), and trifluoromethanesulfonic acid (<b>5</b>) by energy-resolved collision-induced dissociation (CID) tandem mass spectrometry and density functional theory (M06/6-311+G(d,p)). Ion <b>1</b> loses CO₂ at low lab-frame collision energy. Ion <b>2</b> also loses CO₂ to form the 1,1,1-trifluoroethane ion (m/z 83) and 1,2-difluoroethylene to form FCO₂⁻ (m/z 63). RRKM calculations for the two reactions show that m/z 83 has a higher entropy of activation driving its formation. Ion <b>3</b> undergoes the loss of CH₂O to form the pentafluoroethyl anion (m/z 119) and the loss of HF to form CF₂CF₂COH⁻ (m/z 129). Ion <b>4</b> produced four fragment ions with two primary reactions making CF₃CHCH⁻ (m/z 95) + H₂O and CF₂CHCOH₂⁻ (m/z 93) + HF, which go on to dissociate further to produce CF₃⁻ (m/z 69) + HCCH + H₂O and CF₂CH⁻ (m/z 63) + CH₂O + HF. At low collision energy, m/z 95 dominates due to a lower energy transition state, but as internal energy increases, m/z 93 takes over as its transition state has a more favorable entropy. Ion <b>5</b> produced FSO₃⁻ (m/z 99), SO₃⁻ (m/z 80), and CF₃⁻ (m/z 69). SO₃⁻ was the most abundant fragment due to its higher electron affinity.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 10","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Herbal Formulation Analysis: The Role of Flash Chromatography and TLC–MS in Purification and Quality Control","authors":"Saurabh Shukla,&nbsp;Shweta Mevada","doi":"10.1002/jms.5172","DOIUrl":"10.1002/jms.5172","url":null,"abstract":"<div>\u0000 \u0000 <p>Herbal formulations, widely used for their therapeutic properties, require rigorous analysis to ensure their safety, efficacy, and consistency. Flash chromatography and thin layer chromatography–mass spectrometry (TLC–MS) are powerful analytical tools that play a crucial role in the purification, identification, and quality control of herbal products. Flash chromatography enables rapid separation and purification of bioactive compounds from complex herbal mixtures, while thin layer chromatography provides a simple and effective method for compound fingerprinting. When coupled with mass spectrometry, thin layer chromatography–mass spectrometry offers highly sensitive and precise identification of individual compounds, facilitating the detection of active ingredients, metabolites, and contaminants. This article explores the principles, techniques, and applications of flash chromatography and thin layer chromatography–mass spectrometry in the analysis of herbal formulations, with a focus on their combined use for the purification and characterization of active constituents. Additionally, it highlights the importance of these methods in quality control, standardization, and regulatory compliance in the herbal industry. Flash chromatography offers a distinct advantage in the rapid and high-resolution separation of complex multi-component herbal matrices, enabling efficient recovery of target bioactives, whereas TLC–MS provides exceptional analytical sensitivity and specificity for the detection and structural elucidation of low-abundance constituents. The combined application of these techniques ensures comprehensive chemical profiling and robust quality control of herbal formulations. By integrating these advanced techniques, researchers and manufacturers can ensure the integrity, potency, and safety of herbal products, paving the way for more effective and reliable herbal medicine.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complexation of Tetraanisolyl–Anthraquinodimethanes With Alkali Metal Ions: A Combined Mass Spectrometric and Computational Study","authors":"Yanyang Chen,&nbsp;Maryam F. Abdollahi,&nbsp;Yuming Zhao,&nbsp;Travis D. Fridgen","doi":"10.1002/jms.5166","DOIUrl":"10.1002/jms.5166","url":null,"abstract":"<div>\u0000 \u0000 <p>In this work, we investigated a group of tetranisolyl-functionalized anthraquinodimethane (TAAQ) derivatives in terms of their binding properties with alkali metal cations (Li⁺, Na⁺, K⁺, Rb⁺, and Cs⁺). These anthraquinodimethane extended tetrathiafulvalenes (TTFAQs) feature preorganized multiple ether groups, enabling them to bind with alkali metal cations in a manner analogous to crown ethers or spherands. The resulting guest–host complexes, M⁺(TAAQ), were analyzed by mass spectrometry through sustained off-resonance irradiation collision-induced dissociation (SORI-CID) to determine their fragmentation behavior in the gas phase. Our findings revealed that, with the exception of Li⁺(TAAQ) and Na⁺(<i>o</i>-TAAQ), all complexes lost the neutral TAAQ moiety, leaving alkali metal cations as fragments. By combining experimental data and density functional theory (DFT) modeling, we deduced the possible dissociation pathways for Li⁺(TAAQ) and Na⁺(<i>o</i>-TAAQ). Furthermore, energy-resolved (ER) SORI-CID analysis allowed for a comparative study of the relative gas-phase stability of M⁺(TAAQ), revealing a stability trend that aligns with the binding energies computed based on the lowest energy structures for these complexes. Through the approach of natural energy decomposition analysis (NEDA), electrostatic interactions (ES) were identified as the key driving force behind the assembly of M⁺(TAAQ).</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Deep Siamese Convolution Network for Detecting Fentanyl Analogs From Mass Spectra","authors":"Zhenchuang Wang,&nbsp;Ping Xu,&nbsp;Yang Zhao,&nbsp;Lingyun Xue,&nbsp;Yian Liu,&nbsp;Ming Yan,&nbsp;Anqi Chen,&nbsp;Shundi Hu,&nbsp;Luhong Wen","doi":"10.1002/jms.5171","DOIUrl":"10.1002/jms.5171","url":null,"abstract":"<div>\u0000 \u0000 <p>Mortality rates have risen dramatically in recent years due to the misuse of fentanyl and its analogs. Due to the easy synthesis and rapid emergence of various fentanyl analogs, an accurate detection model is particularly desirable. The existing classifiers cannot meet the requirements for their accurate detection. For the small sample size detection problem of fentanyl analogs of electron impact (EI) or electrospray ionization (ESI) mass spectra, a novel mass spectra classification model based on deep Siamese convolutional network (DSCN) was proposed. First, the input mass spectra are augmented to be the input mass spectral pairs. Second, 1D CNN is involved in the Siamese network to extract the spectral features. Finally, the classification network based on FC layers and Softmax layer is used to detect the fentanyl analogs. Contrastive loss function and cross-entropy loss function are combined to train the network parameters of DSCN. Experimental results show that, compared with other machine learning and deep learning methods, the proposed DSCN can achieve better performance on the detection of fentanyl analogs.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal Analysis of Oak Wood Metabolites for a Comprehensive Understanding of the Aging Process in Typical French Spirit Barrels","authors":"Aline Cournut,&nbsp;Quentin P. Vanbellingen,&nbsp;Anaïs Demaye,&nbsp;Matthias Ochs,&nbsp;Andreas Römpp,&nbsp;David Touboul,&nbsp;Véronique Eparvier,&nbsp;Alain Brunelle","doi":"10.1002/jms.5170","DOIUrl":"10.1002/jms.5170","url":null,"abstract":"<div>\u0000 \u0000 <p>Oak wood plays a crucial role in barrel aging, significantly influencing the flavor, aroma, and quality of aged spirits. This study integrates liquid chromatography–tandem mass spectrometry (LC–MS/MS), laser desorption/ionization mass spectrometry (LDI-MS), and time-of-flight secondary ion mass spectrometry (TOF-SIMS) to analyze metabolite distribution in oak wood. By comparing freshly cut wood, freshly toasted wood, or historical wood staves of 2- to 50- or 100-year-old, this multimodal approach reveals spatial distribution changes in lignin, polysaccharides, lipids, and extractable compounds such as phenolic ones. Notably, the degradation of polysaccharides and migration of ellagitannins are observed, providing new insights into wood-aging dynamics. These findings offer potential improvements in barrel aging techniques to enhance the sensory profile of spirits.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Candidate Reference Measurement Procedure for Plasma Clozapine Quantification Using ID-LC–MS/MS","authors":"Xiaodong Yang,&nbsp;Minmin Tu,&nbsp;Chunlan Tang,&nbsp;Min Shen,&nbsp;Huoyan Ji","doi":"10.1002/jms.5168","DOIUrl":"10.1002/jms.5168","url":null,"abstract":"<div>\u0000 \u0000 <p>We developed a candidate reference measurement procedure (cRMP) based on isotope dilution liquid chromatography–tandem mass spectrometry (ID-LC–MS/MS) for the accurate quantification of clozapine (CLO) in human plasma. After systematic optimization of chromatographic separation conditions for CLO, we evaluated various sample pretreatment methods. The analytical performance of the cRMP was rigorously validated, encompassing specificity, recovery, precision, linearity, limit of quantitation (LoQ), limit of detection (LoD), carryover, stability, and method comparison. Measurement uncertainties were assessed in accordance with GUM, taking CLO purity, balance weighing, calibration curve, measurement imprecision, recovery, and carryover into account. Under optimized conditions, CLO showed effective separation from potential interferents in human plasma. The method exhibited excellent linearity (<i>R</i>² = 0.9988) across a concentration range of 5.65–1693.51 ng/g. The total coefficients of variation (CVs) were 2.04%, 0.97%, and 0.65% at concentrations of 24.53, 98.06, and 987.02 ng/g, respectively. Average recoveries ranged from 97.80% to 99.28%, with a LoQ of 2.73 ng/g and a LoD of 0.91 ng/g. The expanded measurement uncertainties (<i>U</i>) were 1.3 ng/g (<i>k</i> = 2) at 24.53 ng/g, 3.8 ng/g (<i>k</i> = 2) at 98.06 ng/g, and 35.3 ng/g (<i>k</i> = 2) at 987.02 ng/g. The developed cRMP for CLO quantification demonstrates excellent specificity, accuracy, precision, and traceability, meeting all the criteria for cRMPs. This method has the potential to standardize therapeutic drug monitoring (TDM) for CLO, improving clinical outcomes and patient safety.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 9","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}