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The goal of cystinuria management is to reduce stone formation by increasing cystine solubility in urine, which includes lowering the urinary cystine level below its solubility limit. Treatment usually involves alkalinization of the urine and often requires initiating pharmacotherapy with a cystine-binding thiol drug (CBTD) such as tiopronin; however, proper dose adjustment requires accurate measurement of urinary cystine. The goal of this study was to validate a novel high-performance liquid chromatography tandem mass spectrometry (HPLC\u2013MS\/MS) method for quantification of cystine in the urine of patients with cystinuria receiving a CBTD. Urine samples were collected over 24\u00a0h from 24 patients and separated into 2 aliquots. Chromatographic separation of samples was conducted and separation of cystine from the cysteine-tiopronin drug complex was complete in\u2009&lt;\u20093\u00a0min. The method was validated for accuracy, precision, linearity, limit of detection (LOD), and limit of quantification (LOQ). Mean accuracy range was 97.7\u2013102.3%; intermediate precision was high with relative percent difference values calculated at 1.2\u20139.3%; the calibration curve resulted in a linear response throughout the concentration range (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.998); and the LOD and LOQ were 0.002 and 0.005\u00a0mg\/mL, respectively. Mean (range) cystine concentrations measured were 111.10 (51.31\u2013179.46) and 242.21 (61.14\u2013741.80) g\/L in Aliquots A and B, respectively. The HPLC\u2013MS\/MS method presented here indicates that urine cystine can be reliably quantified in patients receiving a CBTD.<\/jats:p>","DOI":"10.1007\/s00240-022-01364-9","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T10:02:58Z","timestamp":1665050578000},"page":"721-727","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Accurate 24-h urine cystine quantification for patients on cystine-binding thiol drugs"],"prefix":"10.1007","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3040-073X","authenticated-orcid":false,"given":"Charles C.","family":"Mikel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Goldfarb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-357X","authenticated-orcid":false,"given":"Amy","family":"Ponte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-2118","authenticated-orcid":false,"given":"Katherine","family":"Steigelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4050-4863","authenticated-orcid":false,"given":"Sergey","family":"Latyshev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"1364_CR1","doi-asserted-by":"publisher","first-page":"842","DOI":"10.2215\/CJN.06680714","volume":"10","author":"C Prot-Bertoye","year":"2015","unstructured":"Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Bataille P, Bridoux F, Brignon P, Choquenet C, Cochat P, Combe C, Conort P, Decramer S, Dor\u00e9 B, Dussol B, Essig M, Gaunez N, Joly D, Le Toquin-Bernard S, M\u00e9jean A, Meria P, Morin D, N\u2019Guyen HV, No\u00ebl C, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M (2015) CKD and its risk factors among patients with cystinuria. 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AP: Current employee and stockholder of Travere Therapeutics, Inc. KS: Current employee and stockholder of Travere Therapeutics, Inc. SL: Employee of Nightmaker Science, LLC.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"The data used for the analyses in this manuscript are available on request from Travere Therapeutics, Inc., San Diego, CA.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data sharing statements"}},{"value":"Patient samples were de-identified and consent was obtained prior to collection.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Travere Therapeutics, Inc, provided financial and material support for the research and, with the assistance of study investigators, monitored the conduct of the study, collected data from the investigative centers, and analyzed the data. Travere Therapeutics, Inc, also consulted with advisors and study investigators on the study design and assisted the authors in preparation and review of the manuscript. Travere Therapeutics, Inc, provided funding for professional medical writing and editorial assistance to MedVal Scientific Information Services, Princeton, NJ.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Role of sponsor"}}]}}