{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:09:22Z","timestamp":1778310562138,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Liquid chromatography with electrochemical detection (LC\u2010ED) after batch alumina extraction has been the mainstay for assaying levels of catecholamines and related 3,4\u2010dihydroxy compounds (catechols) as part of the clinical laboratory workup of patients with neurogenic orthostatic hypotension, especially in the setting of the autonomic synucleinopathies Parkinson disease with orthostatic hypotension (PD\u2009+\u2009OH), pure autonomic failure (PAF), and multiple system atrophy (MSA). Liquid chromatography with tandem mass spectrometry (LC\u2013MS\/MS) is faster and measures catechols and non\u2010catechol metabolites simultaneously but has not yet been validated sufficiently against LC\u2010ED or used to assess catechol vs. non\u2010catechol neurochemical abnormalities in autonomic synucleinopathies. We measured plasma catechols by LC\u2013MS\/MS and LC\u2010ED in patients with PAF, PD\u2009+\u2009OH, or MSA and healthy controls. Cardiac sympathetic neuroimaging by\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010dopamine positron emission tomography (PET) was used to indicate myocardial norepinephrine (NE) content in the same subjects. Across 41 participants (12 PAF, 9 PD\u2009+\u2009OH, 10 MSA, 10 controls) individual values for plasma 3,4\u2010dihydroxyphenylglycol (DHPG), NE, and 3,4\u2010dihydroxyphenylalanine (DOPA) by LC\u2013MS\/MS correlated positively with values by LC\u2010ED (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.97, 0.98, and 1.00,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001 each). The PAF group had low mean NE, DHPG, normetanephrine, 3\u2010methoxy\u20104\u2010hydroxyphenylglycol, epinephrine, and metanephrine compared to the PD\u2009+\u2009OH group, while cardiac PET did not separate the 2 groups. We therefore conclude that LC\u2013MS\/MS validly assays plasma catechols. Several catechol and non\u2010catechol biomarkers of generalized catecholamine deficiency separate PAF from PD\u2009+\u2009OH but not PD\u2009+\u2009OH from MSA, while\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010dopamine PET separates PAF and PD\u2009+\u2009OH from MSA but not PAF from PD\u2009+\u2009OH. Combining LC\u2013MS\/MS with cardiac sympathetic neuroimaging efficiently differentiates among these conditions.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70405-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70405","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:36:03Z","timestamp":1773300963000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emerging Role of Liquid Chromatography\u2013Mass Spectrometry in the Clinical Laboratory Evaluation of Chronic Autonomic Failure"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5709-9940","authenticated-orcid":false,"given":"David S.","family":"Goldstein","sequence":"first","affiliation":[{"name":"Clinical Neurosciences Program, Division of Intramural Research National Institute of Neurological Disorders and Stroke, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patti","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Program, Division of Intramural Research National Institute of Neurological Disorders and Stroke, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney","family":"Holmes","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Program, Division of Intramural Research National Institute of Neurological Disorders and Stroke, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ido","family":"Kema","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martijn","family":"van Faassen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2024.124098"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(88)90130-0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/32.11.2030"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.56.3.1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-011-0119-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02309628"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000324625.00404.15"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-006-0317-8"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00396.2018"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-018-0528-9"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90786-Z"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113298"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-002-0020-3"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45803"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-133-5-200009050-00009"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2017.10.003"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-011-0136-4"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws055"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000058766.46428.F3"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-016-0388-0"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI172460"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-015-0268-z"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410260410"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.805887"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-025-01150-8"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(93)E0430-X"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.55.3.181"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-019-00644-6"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-024-01035-2"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-017-0495-6"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02291236"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24877"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-82-3-336"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51243"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-023-00987-1"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13190"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI102828"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.50.1.317"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-012-0165-7"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae033"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13052"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1960.03840110025004"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c01263"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197702102960601"}],"container-title":["Journal 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