{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:43:56Z","timestamp":1792637036980,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T00:00:00Z","timestamp":1662163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Parathyroid hormone (PTH) measurement is important for patients with disorders of calcium metabolism, including those needing bone-turnover monitoring due to chronic kidney disease\u2013mineral bone disorder. There are currently 2 generations of PTH immunoassays on the market, both having cross-reactivity issues and lacking standardization. Therefore, we developed an LC-MS\/MS higher-order method for PTH analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The method was calibrated against the international standard for 1-84 PTH (WHO 95\/646). Antibody-free sample preparation with the addition of an isotope-labeled internal standard was performed by solid-phase extraction. Extracts were analyzed by LC-MS\/MS. EDTA-K2 plasma was used throughout the development and validation. Bias and uncertainty sources were tested according to ISO 15193. Clinical Laboratory Standards Institute guidelines and reference measurement procedures were consulted for the design of the validation. Patient samples and external quality controls were compared between LC-MS\/MS and 2 third-generation immunoassays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The method was validated for 1-84 PTH from 5.7 to 872.6\u2005pg\/mL. The interassay imprecision was between 1.2% and 3.9%, and the accuracy ranged from 96.2% to 103.2%. The measurement uncertainty was &amp;lt;5.6%. The comparison between LC-MS\/MS and the immunoassays showed a proportional bias but moderate to substantial correlation between methods.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This LC-MS\/MS method, which is independent of antibodies, is suitable for a wide range of PTH concentrations. The obtained analytical performance specifications demonstrate that development of a reference measurement procedure will be possible once a higher order reference standard is available.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvac135","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T09:40:03Z","timestamp":1662198003000},"page":"1399-1409","source":"Crossref","is-referenced-by-count":34,"title":["Validation of an LC-MS\/MS Method Using Solid-Phase Extraction for the Quantification of 1-84 Parathyroid Hormone: Toward a Candidate Reference Measurement Procedure"],"prefix":"10.1093","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1047-3974","authenticated-orcid":false,"given":"Jordi","family":"Farr\u00e9-Segura","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry, University of Li\u00e8ge (ULi\u00e8ge), CHU de Li\u00e8ge , Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Le Goff","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University of Li\u00e8ge (ULi\u00e8ge), CHU de Li\u00e8ge , Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Lukas","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University of Li\u00e8ge (ULi\u00e8ge), CHU de Li\u00e8ge , Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Cobraiville","sequence":"additional","affiliation":[{"name":"Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), University of Li\u00e8ge (ULi\u00e8ge) , Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Fillet","sequence":"additional","affiliation":[{"name":"Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), University of Li\u00e8ge (ULi\u00e8ge) , Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Catherine","family":"Servais","sequence":"additional","affiliation":[{"name":"Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), University of Li\u00e8ge (ULi\u00e8ge) , Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1480-5761","authenticated-orcid":false,"given":"Pierre","family":"Delanaye","sequence":"additional","affiliation":[{"name":"Department of Nephrology\u2013Dialysis\u2013Transplantation, University of Li\u00e8ge (ULi\u00e8ge), CHU Li\u00e8ge , Li\u00e8ge , Belgium"},{"name":"Department of Nephrology-Dialysis-Apheresis, H\u00f4pital Universitaire Car\u00e9meau , N\u00eemes , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0947-2226","authenticated-orcid":false,"given":"Etienne","family":"Cavalier","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University of Li\u00e8ge (ULi\u00e8ge), CHU de Li\u00e8ge , Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,3]]},"reference":[{"key":"2022110223575259900_hvac135-B1","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1073\/pnas.95.4.1909","article-title":"Parathyroid hormone leads to the lysosomal degradation of the renal type II Na\/Pi cotransporter","volume":"95","author":"Pfister","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022110223575259900_hvac135-B2","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1002\/jbmr.5650101213","article-title":"PTH\/PTHrP receptor expression on osteoblasts and osteocytes but not resorbing bone surfaces in growing rats","volume":"10","author":"Fermor","year":"1995","journal-title":"J Bone Miner Res"},{"key":"2022110223575259900_hvac135-B3","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1001\/jamasurg.2013.104","article-title":"Factors that influence parathyroid hormone half-life: determining if new intraoperative criteria are needed","volume":"148","author":"Leiker","year":"2013","journal-title":"JAMA Surg"},{"key":"2022110223575259900_hvac135-B4","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1172\/JCI110053","article-title":"Metabolism of parathyroid hormone by isolated rat Kupffer cells and hepatocytes","volume":"67","author":"Segre G","year":"1981","journal-title":"J Clin Invest"},{"key":"2022110223575259900_hvac135-B5","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1210\/jcem-63-5-1075","article-title":"Calcium-dependent release of carboxyl-terminal fragments of parathyroid hormone by hyperplastic human parathyroid tissue in vitro","volume":"63","author":"Hanley","year":"1986","journal-title":"J Clin Endocrinol Metab"},{"key":"2022110223575259900_hvac135-B6","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1210\/endo-104-6-1778","article-title":"Effects of plasma calcium concentration on the relative proportion of hormone and carboxyl fragments in parathyroid venous blood","volume":"104","author":"Mayer","year":"1979","journal-title":"Endocrinology"},{"key":"2022110223575259900_hvac135-B7","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1210\/endo-117-1-127","article-title":"Metabolism of radioiodinated carboxy-terminal fragments of bovine parathyroid hormone in normal and anephric rats","volume":"117","author":"D\u2019Amour","year":"1985","journal-title":"Endocrinology"},{"key":"2022110223575259900_hvac135-B8","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1038\/sj.ki.5001599","article-title":"Circulating PTH molecular forms: what we know and what we don\u2019t","volume":"70","author":"D\u2019Amour","year":"2006","journal-title":"Kidney Int"},{"key":"2022110223575259900_hvac135-B9","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1007\/s00198-014-2635-3","article-title":"Comparison of two commercially available ELISAs for circulating sclerostin","volume":"25","author":"Costa","year":"2014","journal-title":"Osteoporos Int"},{"key":"2022110223575259900_hvac135-B10","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1093\/clinchem\/33.8.1364","article-title":"Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia","volume":"33","author":"Nussbaum","year":"1987","journal-title":"Clin Chem"},{"key":"2022110223575259900_hvac135-B11","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/clinchem\/44.4.805","article-title":"A non-(1-84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial 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truncated fragments: implications for PTH measurements in renal failure","volume":"84","author":"John","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2022110223575259900_hvac135-B15","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1359\/jbmr.2001.16.4.605","article-title":"Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1-84: implications for improvement of accurate assessment of parathyroid function","volume":"16","author":"Gao","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2022110223575259900_hvac135-B16","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.kint.2020.12.024","article-title":"Non-oxidized parathyroid hormone (PTH) measured by current method is not superior to total PTH in assessing bone turnover in chronic kidney disease","volume":"99","author":"Ursem","year":"2021","journal-title":"Kidney 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(normal) values","volume":"27","author":"Cavalier","year":"2012","journal-title":"Nephrol Dial Transplant"},{"key":"2022110223575259900_hvac135-B25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.clinbiochem.2018.02.019","article-title":"Establishment of reference values in a healthy population and interpretation of serum PTH concentrations in hemodialyzed patients according to the KDIGO guidelines using the lumipulse\u00ae G whole PTH (3rd generation) assay","volume":"54","author":"Cavalier","year":"2018","journal-title":"Clin Biochem"},{"key":"2022110223575259900_hvac135-B26","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1021\/ac9026862","article-title":"Development of a candidate reference measurement procedure for the determination of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D 2 in human serum using isotope-dilution liquid chromatography tandem mass spectrometry","volume":"82","author":"Tai","year":"2010","journal-title":"Anal Chem"},{"key":"2022110223575259900_hvac135-B27","doi-asserted-by":"crossref","first-page":"7964","DOI":"10.1021\/acs.analchem.5b01861","article-title":"Candidate reference measurement procedure for the determination of (24 R),25-dihydroxyvitamin D3 in human serum using isotope-dilution liquid chromatography-tandem mass spectrometry","volume":"87","author":"Tai","year":"2015","journal-title":"Anal Chem"},{"key":"2022110223575259900_hvac135-B28","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1373\/clinchem.2013.220392","article-title":"Mass spectrometry-based candidate reference measurement procedure for quantification of amyloid-\u03b2 in cerebrospinal fluid","volume":"60","author":"Leinenbach","year":"2014","journal-title":"Clin Chem"},{"key":"2022110223575259900_hvac135-B29","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1093\/clinchem\/hvaa324","article-title":"Development of an LC-MS\/MS proposed candidate reference method for the standardization of analytical 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