{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:50:20Z","timestamp":1785354620013,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T00:00:00Z","timestamp":1567900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amitriptyline (AMI) has been in use for decades in treating depression and more recently for the management of neuropathic pain. A highly sensitive and specific LC\u2013tandem mass spectrometry method was developed for simultaneous determination of AMI, its active metabolite nortriptyline (NOR) and their hydroxy\u2010metabolites in human serum, using deuterated AMI and NOR as internal standards. The isobaric E\u201010\u2010hydroxyamitriptyline (E\u2010OH AMI), Z\u201010\u2010hydroxyamitriptyline (Z\u2010OH AMI), E\u201010\u2010hydroxynortriptyline (E\u2010OH NOR) and Z\u201010\u2010hydroxynortriptyline (Z\u2010OH NOR), together with their parent compounds, were separated on an ACE C<jats:sub>18<\/jats:sub> column using a simple protein precipitation method, followed by dilution and analysis using positive electrospray ionisation with multiple reaction monitoring. The total run time was 6\u2009min with elution of E\u2010OH AMI, E\u2010OH NOR, Z\u2010OH AMI, Z\u2010OH NOR, AMI (+ deuterated AMI) and NOR (+ deuterated NOR) at 1.21, 1.28, 1.66, 1.71, 2.50 and 2.59\u2009min, respectively. The method was validated in human serum with a lower limit of quantitation of 0.5\u2009ng\/mL for all analytes. A linear response function was established for the range of concentrations 0.5\u2013400\u2009ng\/mL (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u2009&gt;\u2009.999). The practical assay was applied on samples from patients on AMI, genotyped for <jats:italic>CYP2C19<\/jats:italic> and <jats:italic>CYP2D6<\/jats:italic>, to understand the influence of metaboliser status and concomitant medication on therapeutic drug monitoring.<\/jats:p>","DOI":"10.1002\/bmc.4679","type":"journal-article","created":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T10:24:30Z","timestamp":1565864670000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Practical liquid chromatography\u2013tandem mass spectrometry method for the simultaneous quantification of amitriptyline, nortriptyline and their hydroxy metabolites in human serum"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0019-2669","authenticated-orcid":false,"given":"Luana","family":"Mifsud Buhagiar","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Surgery University of Malta  Msida Malta"},{"name":"Malta Medicines Authority Life Sciences Park  San \u0120wann Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1895-3398","authenticated-orcid":false,"given":"Carmel","family":"Sammut","sequence":"additional","affiliation":[{"name":"Department of Pathology Mater Dei Hospital  Msida Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Chircop","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Surgery University of Malta  Msida Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kersty","family":"Axisa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Surgery University of Malta  Msida Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolette","family":"Sammut Bartolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Surgery University of Malta  Msida Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis","family":"Vella Szijj","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Surgery University of Malta  Msida Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Serracino Inglott","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine and Surgery University of Malta  Msida Malta"},{"name":"Malta Medicines Authority Life Sciences Park  San \u0120wann Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godfrey","family":"LaFerla","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Surgery University of Malta  Msida Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.178.2.129"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-198604000-00002"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2001.01548.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.1435"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.10.89"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2010.02.067"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1081\/DMR-200033482"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bkv024"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.5012\/bkcs.2012.33.7.2163"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2013.09.001"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32802-7"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/34.2.64"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/34.5.841"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2008.05.024"},{"key":"e_1_2_8_16_1","unstructured":"Dean L. 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