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Analysis of institutional authors

Zamora Guardiola, AlbertAuthorCasals, GregoriCorresponding AuthorZamora, AngielysAuthorMartinez, IreneAuthorFernandez-Varo, GuillermoAuthorHanzu, Felicia ACorresponding AuthorMorales-Ruiz, ManuelAuthor

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June 10, 2024
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Article

LC-HRMS and GC-MS Profiling of Urine Free Cortisol, Cortisone, 6Β-, and 18-Hydroxycortisol for the Evaluation of Glucocorticoid and Mineralocorticoid Disorders

Publicated to: Biomolecules. 14 (5): 558- - 2024-05-01 14(5), DOI: 10.3390/biom14050558

Authors: Casals, Gregori; Ballesteros, Maria Antonieta; Zamora, Angielys; Martinez, Irene; Fernandez-Varo, Guillermo; Mora, Mireia; Hanzu, Felicia A; Morales-Ruiz, Manuel

Affiliations

Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Biochem & Mol Genet Dept, Barcelona 08036, Spain - Author
Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Dept Endocrinol & Nutr, Barcelona 08036, Spain - Author
Hosp Gen Univ Gregorio Maranon, Dept Clin Biochem, Madrid 28007, Spain - Author
Hosp Univ Son Espases, Serv Clin Anal, Palma De Mallorca 07210, Spain - Author
Univ Barcelona, Fac Med & Hlth Sci, Dept Biomed, Barcelona 08036, Spain - Author
Univ Barcelona, Fac Med & Hlth Sci, Dept Med, Barcelona 08036, Spain - Author
Univ Barcelona, Fac Nursing, Dept Fundamental & Clin Nursing, Barcelona 08036, Spain - Author
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Abstract

Introduction: Urine free cortisol measurements are routinely performed to evaluate hypercortisolism. Despite their analytical inaccuracy, immunoassay-based methods are frequently used. Advances in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) facilitate the incorporation of powerful diagnostic tools into clinical laboratories. In addition to its high analytical specificity and simultaneous analysis of different metabolites, accurate mass measurement allows for untargeted compound identification, which may help to identify clinically relevant metabolites or drugs. Methods: The present study aimed to validate a simple routine LC-HRMS method to quantify cortisol, cortisone, 6 beta-hydroxycortisol, and 18-hydroxycortisol simultaneously in human urine. Additionally, the study also validated a GC-MS method for the same steroids, evaluated their cross-reactivity with commercial cortisol immunoassays, and quantified the 24 h urine excretion in patients under clinical suspicion or follow-up for hypercortisolism. Results: The LC-HRMS method involved liquid-liquid extraction using dichloromethane, micro-LC for chromatographic separation and detection using the accurate masses of the steroids, and simultaneous high-resolution full scan acquisition. The method presented acceptable linearity, precision, and accuracy. Significant interference from 6 beta-hydroxycortisol and cortisone was demonstrated in the cortisol immunoassays, which impacted their reliability in the follow-up of patients with hypercortisolism and significant changes in these cortisol metabolites (i.e., due to drug-induced changes in CYP3A4 activity). Conclusion: A rapid and accurate routine LC-HRMS method was validated, which is useful for the evaluation of hypercortisolism and other disorders of glucocorticoid and mineralocorticoid metabolism.

Keywords

18 hydroxyhydrocortisone6 beta-hydroxycortisol6beta hydroxyhydrocortisoneAccuracyAdultAgedArticleChemical structureChromatography, liquidClinical articleControlled studyCortisonCortisonaCortisoneCromatografia de líquidsCushing syndromeCushing's syndromeCushing’s syndromeCytochrome p450 3a4DiagnosisDichloromethaneElectrosprayFemaleGas chromatography-mass spectrometryGlucocorticoidGlucocorticoid disorderGlucocorticoidsHigh performance liquid chromatographyHigh-resolution mass spectrometryHormone determinationHumanHumansHydrocortisoneHypercortisolismImmunoassayKetoconazoleLimit of detectionLimit of quantitationLiquid chromatographyLiquid chromatography-mass spectrometryLiquid liquid extractionLiquid phase microextractionMaleMass fragmentographyMass spectrometryMeasurement accuracyMeasurement precisionMetabolomicsMicro-liquid chromatographyMineralocorticoidMineralocorticoid disorderMs/ms methodMultiple reaction monitoringPhenol derivativeProceduresQuantificationRatiReliabilityRetention timeReversed phase high performance liquid chromatographySerumSíndrome de cushingTandem mass-spectrometryTyrosineUltra performance liquid chromatographyUrinalysisUrinary excretionUrineUrine free cortisolValidationValidation process

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Biomolecules due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 75/319, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-06:

  • WoS: 4
  • Scopus: 2
  • Europe PMC: 2

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-06:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 18.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 17 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/2445/222548

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Casals Mercadal, Gregori) and Last Author (Morales Ruiz, Manuel).

the authors responsible for correspondence tasks have been Casals Mercadal, Gregori and Hanzu, Felicia Alexandra.

Awards linked to the item

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