Clinical chemistry and laboratory medicine最新文献

{"title":"IgA-type macroprolactin among 130 patients with macroprolactinemia.","authors":"Masayuki Ishihara, Naoki Hattori, Norito Nishiyama, Kozo Aisaka, Takashi Adachi, Takanori Saito","doi":"10.1515/cclm-2025-0264","DOIUrl":"https://doi.org/10.1515/cclm-2025-0264","url":null,"abstract":"<p><strong>Objectives: </strong>Macroprolactin (macro-PRL) mostly comprises a complex of PRL with IgG. The aim of this study was to clarify whether IgA-type macro-PRL exists and, if so, to elucidate the prevalence of and differences in laboratory data from IgG-type.</p><p><strong>Methods: </strong>One hundred thirty patients with macroprolactinemia who were diagnosed through screening via the polyethylene glycol precipitation method followed by confirmation using gel filtration chromatography (GFC) were examined. IgA-type and IgG-type macro-PRLs were identified via Jacalin column/SDS‒PAGE and protein G columns, respectively.</p><p><strong>Results: </strong>SDS‒PAGE under nonreducing conditions followed by western blotting with an IgA antibody revealed that the fraction bound to the Jacalin column was actually IgA. The PRL band was detected at the same position as the IgA band, which was purified with a Jacalin column, suggesting that PRL was bound to IgA. The finding that the PRL band was observed not only at the same position as IgA but also at the same position as the 23 kDa PRL reference suggested that some PRL dissociated from IgA during SDS‒PAGE. The prevalence rates of macro-PRL of only IgA, IgA plus IgG, only IgG, and non-IgA/non-IgG types were 7.7, 3.1, 83.8, and 5.4 %, respectively. Neither the PEG precipitation ratios of PRL nor the macro-PRL ratios on GFC differed between IgA- and IgG-type macro-PRLs, whereas both ratios were significantly lower in non-IgA/non-IgG-type macro-PRL.</p><p><strong>Conclusions: </strong>IgA-type macro-PRL was demonstrated to exist. IgG-type macro-PRL was most prevalent, followed by IgA, non-IgA/non-IgG and IgA plus IgG-type macro-PRLs.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid chromatography tandem mass spectrometry (LC-MS/MS) candidate reference measurement procedure for urine albumin.","authors":"Seiei Shiba, Zoi E Sychev, Michael D Evans, Jesse C Seegmiller","doi":"10.1515/cclm-2024-1374","DOIUrl":"https://doi.org/10.1515/cclm-2024-1374","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the efficiency of quality control in clinical laboratory with an integrated PBRTQC system based on patient risk.","authors":"Xincen Duan, Tony Badrick, Wenqi Shao, Andreas Bietenbeck, Xiao Tan, Jing Zhu, Wenhai Jiang, Ying Zhao, Chunyan Zhang, Baishen Pan, Beili Wang, Wei Guo","doi":"10.1515/cclm-2025-0163","DOIUrl":"https://doi.org/10.1515/cclm-2025-0163","url":null,"abstract":"<p><strong>Objectives: </strong>Recent advances in information technology have renewed interest in patient-based real-time quality control (PBRTQC) as an alternative to internal quality control (IQC). However, since regulations mandate IQC, PBRTQC can only be implemented as a separate system. The additional labor required for PBRTQC may hinder widespread adoption. Therefore, a more efficient system that integrates IQC with PBRTQC is needed for laboratories to implement the methods effectively.</p><p><strong>Methods: </strong>A QC system that integrates IQC with PBRTQC is proposed. The maximum average number of patients with unacceptable analytical errors (MaxANP_TE) was introduced as a critical metric to benchmark the efficiency of the integrated PBRTQC system against the IQC-only system using a modified Parvin patient risk model. With the historical data of serum sodium (Na), chloride (Cl), alanine aminotransferase (ALT), and creatinine (CREA) from Zhongshan Hospital, Fudan University, in 2019, the integrated system incorporating the simple PBRTQC model and the more advanced regression-adjusted real-time quality control (RARTQC) were compared with the IQC-only system.</p><p><strong>Results: </strong>In most cases, the integrated system incorporating RARTQC models outperformed the IQC-only system, particularly for ALT, where QC events were reduced by up to 45 %. Based on these findings, we proposed strategies for laboratories to design the integrated system.</p><p><strong>Conclusions: </strong>The study demonstrated the improvement of efficiency of the integrated PBRTQC system over the IQC-only system. These insights can help laboratories make informed decisions on adopting PBRTQC models and provide as evidence for revising regulation on IQC.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus instability equations for routine coagulation tests.","authors":"Rubén Gómez Rioja, Andrea Caballero Garralda, Immaculada Comas Reixach, Carlos García Miralles, María Antonia Llopis Díaz, Débora Martínez Espartosa, Reyes Nicolás de Blas, Mariona Panadès Turró, Laura Puigví Fernández, Laura Rodelgo Jiménen, Berta Sufrate-Vergara, Emma Ventura Orriols","doi":"10.1515/cclm-2025-0117","DOIUrl":"https://doi.org/10.1515/cclm-2025-0117","url":null,"abstract":"<p><strong>Objectives: </strong>The stability of plasma samples for basic coagulation tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), has been widely studied. Recently, the Clinical and Laboratory Standards Institute (CLSI) updated its recommendations, extending the acceptable time frame for aPTT. These guidelines are based on experimental studies, which define limits according to different maximum permissible error (MPE) criteria. This study compiles raw data from 43 studies published over the last 30 years to develop a consensus instability equation that describes degradation independently of specific study parameters.</p><p><strong>Methods: </strong>A critical literature review was performed by collecting studies that included experimental stability data for PT, aPTT and the main procoagulant factors. The raw data of percentage deviation (PD%), time, and seven classification variables related to sample collection and handling were analysed. A regression model through the origin was applied to derive global instability equations and to assess influencing variables.</p><p><strong>Results: </strong>In frozen samples, PT and aPTT showed similar stability, with an average prolongation of 0.8 % per month. In non-frozen samples, tube handling affected stability more than storage temperature. The consensus equation for PT showed a linear average deterioration of 2.9 % per day, but model strength was limited. For aPTT, the consensus equation fitted better to a logarithmic decay model and predicted prolongations of 6.1 and 10 % at 6 and 24 h, respectively.</p><p><strong>Conclusions: </strong>The consensus instability equations obtained in this review provide a robust model for assessing coagulation tests stability, aligning with expert recommendations. These equations improve the understanding of sample degradation and systematic error quantification.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Mindray high sensitivity cardiac troponin I assay for single sample and 0/2-hour rule out of myocardial infarction: MERITnI study.","authors":"Kevin G Buda, Yader Sandoval, Stephen W Smith, Barrett Wagner, Karen Schulz, Anne Sexter, Fred S Apple","doi":"10.1515/cclm-2024-1387","DOIUrl":"https://doi.org/10.1515/cclm-2024-1387","url":null,"abstract":"<p><strong>Objectives: </strong>We determined the efficacy of a high sensitivity cardiac troponin I (hs-cTnI) assay for newly derived 0 h and 0/2-h rule-out concentrations for myocardial infarction and determined the safety of incremental changes at low concentrations.</p><p><strong>Methods: </strong>Consecutive, emergency department patients undergoing serial hs-cTnI testing on clinical indication were studied in the 'Mindray hs-cTnI Assay Analytical and Clinical Evaluation for the Diagnosis and RIsk Assessment of Myocardial InfarctIon' (MERITnI) trial. Primary safety outcome was the composite of cardiac death and MI at 30 days.</p><p><strong>Results: </strong>In 1,556 patients (60.7 % male, 43.3 % White, 45.8 % Black. 34.8 % chest pain), 26.9 % patients had at least one hs-cTnI >99th percentile. 2.7 % had type 1 MI, 2.7 % type 2 MI, and 21.5 % non-MI myocardial injury. Single-sample MI rule-out using a normal ECG plus hs-cTnI of <2 ng/L (rounded) ruled out 13.8 % of patients, including early (<2 h) presenters. A 2-h delta of <2 ng/L ruled out an additional 39 % of patients. Based on European Society of Cardiology guidance, derived 0 h<15 ng/L and derived delta of <5 ng/L ruled out 42 % of patients. The Mindray assay showed incremental (non-rounded) analysis discriminated rule out from baseline of <0.1 ng/L at 1.2 % to 2.0 ng/L at 17.0 %. There were no missed adverse outcomes at 30-day assessment for composite of MI and cardiac death.</p><p><strong>Conclusions: </strong>The novel Mindray hs-cTnI assay enabled safe and early rule out of MI and cardiac death at very low concentrations in a diverse, cohort utilizing both single sample and 0/2-h rule out protocols, including early presenters.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Lab Error Finder</i>: A call for collaboration.","authors":"Hikmet Can Çubukçu","doi":"10.1515/cclm-2025-0317","DOIUrl":"https://doi.org/10.1515/cclm-2025-0317","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted proteomics of serum IGF-I, -II, IGFBP-2, -3, -4, -5, -6 and ALS.","authors":"Jakob Albrethsen, Lylia Drici, Lea Marie Slot Vilmann, Stine A Holmboe, Charlotte Ehlers Thomsen, Veronica Lykke Rogaczewska Groendahl, Maud Eline Ottenheijm, Annelaura Bach Nielsen, Christina Christoffersen, Lise Aksglaede, Casper P Hagen, Nicolai J Wewer Albrechtsen, Anders Juul","doi":"10.1515/cclm-2024-1428","DOIUrl":"https://doi.org/10.1515/cclm-2024-1428","url":null,"abstract":"<p><strong>Objectives: </strong>The insulin-like growth factors (IGFs) regulate growth in humans. IGF-I and IGF binding protein (IGFBP)-3 are biomarkers in children with growth disorders. We investigate a targeted proteomics method for absolute quantitation of eight IGF protein family members in human serum, including the peptide hormones IGF-I and -II, and the six binding proteins IGFBP-2, -3, -4, -5, -6 and acid labile subunit (ALS).</p><p><strong>Methods: </strong>Serum preparation was optimized for targeted proteomics of IGF related proteins on a clinical LC-MS/MS platform (UHPLC coupled with Triple-Q MS). We created quality controls, standards and internal standards and 289 serum samples from healthy children and adolescents were measured in ten batches over two months. The method was compared to WHO reference standards, clinical and research immunoassays, and relative proteomics profiling.</p><p><strong>Results: </strong>The sensitivity and reproducibility were sufficient for most but not all IGF protein family members. Targeted proteomics correlated well with clinical immunoassays for IGF-I (R²=0.88) and for IGFBP-3 (R²=0.46), (p<0.001). The correlation between targeted proteomics and non-clinical immunoassays for IGF-II, IGFBP-2, -4, -5, -6 and ALS varied between proteins.</p><p><strong>Conclusions: </strong>We present a method for parallel quantification of IGF-I, IGFBP-3, 5 and ALS for clinical verification studies, whereas targeted proteomics of the five remaining IGF related proteins (IGF-II, IGFBP-2, -4, and -6) require further examination. The sensitivity of our new IGF-I method suggests a possible diagnostic role for targeted proteomics of IGF-I in the management of children with extremely low levels of circulating IGF-I.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of the BIOGROUP^® French laboratories database to conduct CKD observational studies: a pilot EPI-CKD1 study.","authors":"Claire Visseaux, Guillaume Pénaranda, Cécile Conte, Fanny Raguideau, Julien L'hirondel, Claire Vignault, Philippe Zaoui, Isabelle Sebaoun-Rivière","doi":"10.1515/cclm-2024-1399","DOIUrl":"https://doi.org/10.1515/cclm-2024-1399","url":null,"abstract":"<p><strong>Objectives: </strong>Medical biology is essential for diagnosing and monitoring cardio-reno-metabolic diseases. The EPI-CKD1 study utilizes data from Biogroup^® French laboratories to examine the burden of chronic kidney disease (CKD) and the effect of heart failure, and diabetes in an outpatient setting in order to address gaps in national databases that lack biological data.</p><p><strong>Methods: </strong>All adults (≥18 years) with at least one blood creatinine test between January 1st of 2021, and June 30th of 2022 were included. Key biomarkers measured included serum creatinine, estimated glomerular filtration rate (eGFR), hemoglobin A_1c, B-type natriuretic peptide (BNP), NT-Pro BNP, and urinary albumin/creatinine ratio (uACR).</p><p><strong>Results: </strong>Among a total of 4,061,208 adults with at least one blood creatinine test, 465,225 (11.5 %) had altered kidney function. Their mean age was 57.9 years (SD 18.8), with 56.7 % women. Diabetes was present in 8.3 %, and heart failure in 1.4 %. Altered kidney function standardized prevalence was estimated to 8.06 %, with an incidence of 5.10 %. Patients with end-stage CKD had an average of 7.9 eGFR measurements, compared to 2 for those with eGFR >60 mL/min/1.73 m². Older age, diabetes, and heart failure were associated with an increased risk of eGFR <60 mL/min/1.73 m².</p><p><strong>Conclusions: </strong>The EPI-CKD1 study demonstrates the utility of Biogroup^® data for large-scale observational studies, offering precise, medically relevant insights on patients at cardio-renal risk. Future studies should focus on data enrichment and long-term follow-up to deepen understanding.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reliable detection of sex chromosome abnormalities by quantitative fluorescence polymerase chain reaction.","authors":"Camilla Mains Balle, Dorte L Lildballe, Ivonne Bedei, Ruth Luschka, Anne Skakkebæk, Simon Chang, Zeynep Agirman, Jan Keller, Axel Weber, Ramón E Schäfer, Johannes Becker-Follmann, Claus H Gravholt","doi":"10.1515/cclm-2024-1400","DOIUrl":"https://doi.org/10.1515/cclm-2024-1400","url":null,"abstract":"<p><strong>Objectives: </strong>Many patients with sex chromosome abnormalities (SCAs) are diagnosed late in life or remain undiagnosed, leading to delayed or inadequate medical intervention and care. This study aimed to develop a reliable, rapid and cost-effective test for identifying SCAs using a blood sample - an essential step toward establishing a neonatal screening program.</p><p><strong>Methods: </strong>A total of 360 blood samples (180 SCA patients, and 180 controls) were obtained from four cross-sectional studies of adult patients with SCAs and age-matched controls. Informed consent was collected, and all procedures followed the Declaration of Helsinki. Multiplex quantitative fluorescence polymerase chain reaction (QF-PCR) utilizing short tandem repeat (STR) and X-linked segmental duplication (SD) markers was performed. Results were analyzed using an automated algorithm. Deviant results were manually reviewed to differentiate errors in the PCR process from those in automated data analysis.</p><p><strong>Results: </strong>Following automated data analysis of QF-PCR results, the method accurately identified 174 SCA patients (sensitivity: 96.7 %) and 171 controls (specificity: 95.0 %). Mosaic karyotypes were particularly challenging to diagnose. Manual reanalysis of the QF-PCR results corrected all false positives, achieving 100 % specificity.</p><p><strong>Conclusions: </strong>This method is promising for reliable SCA detection in blood samples, offering cost-effectiveness and scalability. The specificity following automated data analysis was not satisfactory. The underlying PCR technique, however, demonstrated 100 % specificity, indicating that refining the automated analysis algorithm would significantly reduce false positive results. With further refinements, we believe this test would be highly suitable for further evaluation in a newborn screening setting.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel protocol for metabolomics data normalization and biomarker discovery in human tears.","authors":"Joan Serrano-Marín, Silvia Marin, Alberto Iglesias, Jaume Lillo, Claudia Garrigós, Toni Capó, Irene Reyes-Resina, Hanan Awad Alkozi, Marta Cascante, Juan Sánchez-Navés, Rafael Franco, David Bernal-Casas","doi":"10.1515/cclm-2024-1360","DOIUrl":"https://doi.org/10.1515/cclm-2024-1360","url":null,"abstract":"<p><strong>Objectives: </strong>Human tear analysis holds promise for biomarker discovery, but its clinical utility is hindered by the lack of standardized reference values, limiting interindividual comparisons. This study aimed at developing a protocol for normalizing metabolomic data from human tears, enhancing its potential for biomarker identification.</p><p><strong>Methods: </strong>Tear metabolomic profiling was conducted on 103 donors (64 females, 39 males, aged 18-82 years) without ocular pathology, using the AbsoluteIDQ™ p180 Kit for targeted metabolomics. A predictive normalization model incorporating age, sex, and fasting time was developed to correct for interindividual variability. Key metabolites from six compound families (amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, and sphingomyelins) were identified as normalization references. The approach was validated using Linear Discriminant Analysis (LDA) to test its ability to classify donor sex based on metabolite concentrations.</p><p><strong>Results: </strong>Metabolite concentrations exhibited significant interindividual variability. The normalization model, which predicted metabolite concentrations based on a reference \"concomitant\" metabolite from each compound family, successfully reduced this variability. Using the ratio of observed-to-predicted concentrations, the model enabled robust comparisons across individuals. LDA classification of donor sex using acylcarnitine C4 achieved 78 % accuracy, correctly identifying 92 % of female donors. This approach outperformed traditional statistical and machine learning methods (Lasso logistic regression and Random Forest classification) in sex discrimination based on tear metabolomics.</p><p><strong>Conclusions: </strong>This novel normalization protocol significantly improves the reliability of tear metabolomics by enabling standardized interindividual comparisons. The approach facilitates biomarker discovery by mitigating variability in metabolite concentrations and may be extended to other biological fluids, enhancing its applicability in precision medicine.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}