{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:20:28Z","timestamp":1792808428059,"version":"4.5.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Innsbruck and Medical University of Innsbruck"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Anal Bioanal Chem"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mass spectral library annotation of liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS\/MS) data is a reliable approach for fast identification of organic contaminants and toxicants in complex environmental and biological matrices. While determining the exposure of humans or mammals, it is indispensable to include phase I and phase II metabolites (conjugates) along with the parent compounds, but often, tandem mass spectra for these are unavailable. In this study, we present and evaluate a strategy for annotating glucuronide conjugates in LC-HRMS\/MS scans by applying a neutral loss search for detection, then truncating the spectra which we refer to as in silico deconjugation, and finally searching these against mass spectral libraries of the aglycones. The workflow was tested on a dataset of in vitro\n                    <jats:italic>\u2013<\/jats:italic>\n                    generated glucuronides of reference standard mixtures and a dataset of 51 authentic urine samples collected from patients with known medication status, acquired on different instrumentations. A total number of 75 different glucuronidated molecular structures were identified by in silico deconjugation and spectral library annotation. We also identified specific molecular structures (sulfonamides, ether bonds, di-glucuronides), which resulted in slightly different fragmentation patterns between the glucuronide and the unconjugated compound. This led to a decreased spectral matching score and in some cases to a false-negative identification. Still, by applying this method, we revealed a reliable annotation of most common glucuronides, leading to a new strategy reducing the need for deconjugation steps or for recording many reference glucuronide spectra for screening approaches.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s00216-022-03899-7","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T10:07:28Z","timestamp":1643191648000},"page":"2629-2640","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["In silico deconjugation of glucuronide conjugates enhances tandem mass spectra library annotation of human samples"],"prefix":"10.1007","volume":"414","author":[{"given":"Carolin","family":"Huber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Krauss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Reinstadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Denicol\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Brack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Oberacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"3899_CR1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.aca.2013.01.057","volume":"770","author":"H Oberacher","year":"2013","unstructured":"Oberacher H, Schubert B, Libiseller K, Schweissgut A. Detection and identification of drugs and toxicants in human body fluids by liquid chromatography\u2013tandem mass spectrometry under data-dependent acquisition control and automated database search. Anal Chim Acta. 2013;770:121\u201331. https:\/\/doi.org\/10.1016\/j.aca.2013.01.057.","journal-title":"Anal Chim Acta"},{"key":"3899_CR2","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1021\/es5002105","volume":"48","author":"EL Schymanski","year":"2014","unstructured":"Schymanski EL, Jeon J, Gulde R, Fenner K, Ruff M, Singer HP, Hollender J. Identifying small molecules via high resolution mass spectrometry: communicating confidence. Environ Sci Technol. 2014;48:2097\u20138. https:\/\/doi.org\/10.1021\/es5002105.","journal-title":"Environ Sci Technol"},{"key":"3899_CR3","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1097\/00004714-200110000-00008","volume":"21","author":"HL Liston","year":"2001","unstructured":"Liston HL, Markowitz JS, DeVane CL. Drug glucuronidation in clinical psychopharmacology. J Clin Psychopharmacol. 2001;21:500\u201315. https:\/\/doi.org\/10.1097\/00004714-200110000-00008.","journal-title":"J Clin Psychopharmacol"},{"key":"3899_CR4","doi-asserted-by":"publisher","unstructured":"Coleman, M.D. (2010) Conjugation and transport processes. In: Human drug metabolism. John Wiley & Sons, Ltd, pp 125\u2013157. https:\/\/doi.org\/10.1002\/9780470689332.ch6","DOI":"10.1002\/9780470689332.ch6"},{"key":"3899_CR5","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1080\/03602532.2017.1293682","volume":"49","author":"G Yang","year":"2017","unstructured":"Yang G, Ge S, Singh R, Basu S, Shatzer K, Zen M, Liu J, Tu Y, Zhang C, Wei J, Shi J, Zhu L, Liu Z, Wang Y, Gao S, Hu M. Glucuronidation: driving factors and their impact on glucuronide disposition. Drug Metab Rev. 2017;49:105\u201338. https:\/\/doi.org\/10.1080\/03602532.2017.1293682.","journal-title":"Drug Metab Rev"},{"key":"3899_CR6","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1039\/C3NP70003H","volume":"30","author":"AV Stachulski","year":"2013","unstructured":"Stachulski AV, Meng X. Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides. Nat Prod Rep. 2013;30:806\u201348. https:\/\/doi.org\/10.1039\/C3NP70003H.","journal-title":"Nat Prod Rep"},{"key":"3899_CR7","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1124\/dmd.104.000794","volume":"32","author":"JA Williams","year":"2004","unstructured":"Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE. Drug-drug interactions for Udp-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi\/Auc) ratios. Drug Metab Dispos. 2004;32:1201\u20138. https:\/\/doi.org\/10.1124\/dmd.104.000794.","journal-title":"Drug Metab Dispos"},{"key":"3899_CR8","volume-title":"Human biomonitoring for environmental chemicals","author":"National Research Council","year":"2006","unstructured":"National Research Council. Human biomonitoring for environmental chemicals. Washington, DC: The National Academies Press; 2006."},{"key":"3899_CR9","doi-asserted-by":"publisher","first-page":"S53","DOI":"10.1016\/j.toxac.2015.03.081","volume":"27","author":"AM Taylor","year":"2015","unstructured":"Taylor AM, Cabrices OG, Lee LA, Wang A, Morla A. Automated sample hydrolysis for a forensic toxicology urine screening LC-MS\/MS method. Toxicologie Analytique et Clinique. 2015;27:S53\u20134. https:\/\/doi.org\/10.1016\/j.toxac.2015.03.081.","journal-title":"Toxicologie Analytique et Clinique"},{"key":"3899_CR10","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1093\/jat\/bku142","volume":"39","author":"H Toshima","year":"2015","unstructured":"Toshima H, Yoshinaga J, Shiraishi H, Ito Y, Kamijima M, Ueyama J. Comparison of different urine pretreatments for biological monitoring of pyrethroid insecticides. J Anal Toxicol. 2015;39:133\u20136. https:\/\/doi.org\/10.1093\/jat\/bku142.","journal-title":"J Anal Toxicol"},{"key":"3899_CR11","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.chemosphere.2018.01.177","volume":"199","author":"P Dwivedi","year":"2018","unstructured":"Dwivedi P, Zhou X, Powell TG, Calafat AM, Ye X. Impact of enzymatic hydrolysis on the quantification of total urinary concentrations of chemical biomarkers. Chemosphere. 2018;199:256\u201362. https:\/\/doi.org\/10.1016\/j.chemosphere.2018.01.177.","journal-title":"Chemosphere"},{"key":"3899_CR12","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1093\/jat\/26.2.73","volume":"26","author":"P Crabbe","year":"2002","unstructured":"Crabbe P, Pieraccini G, Bartolucci G, Moneti G, Van Peteghem C. Influence of Helix pomatia enzyme preparations on the oxidative conversion of some clostebol acetate metabolites in urine. J Anal Toxicol. 2002;26:73\u201380. https:\/\/doi.org\/10.1093\/jat\/26.2.73.","journal-title":"J Anal Toxicol"},{"key":"3899_CR13","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.chroma.2004.08.165","volume":"1067","author":"K Levsen","year":"2005","unstructured":"Levsen K, Schiebel H-M, Behnke B, D\u00f6tzer R, Dreher W, Elend M, Thiele H. Structure elucidation of phase II metabolites by tandem mass spectrometry: an overview. J Chromatogr A. 2005;1067:55\u201372. https:\/\/doi.org\/10.1016\/j.chroma.2004.08.165.","journal-title":"J Chromatogr A"},{"key":"3899_CR14","doi-asserted-by":"publisher","first-page":"5005","DOI":"10.1021\/ac4001749","volume":"85","author":"A Fabregat","year":"2013","unstructured":"Fabregat A, Pozo OJ, Marcos J, Segura J, Ventura R. Use of LC-MS\/MS for the open detection of steroid metabolites conjugated with glucuronic acid. Anal Chem. 2013;85:5005\u201314. https:\/\/doi.org\/10.1021\/ac4001749.","journal-title":"Anal Chem"},{"key":"3899_CR15","doi-asserted-by":"publisher","first-page":"A0036","DOI":"10.5702\/massspectrometry.A0036","volume":"4","author":"T Ogura","year":"2015","unstructured":"Ogura T, Bamba T, Tai A, Fukusaki E. Method for the compound annotation of conjugates in nontargeted metabolomics using accurate mass spectrometry, multistage product ion spectra and compound database searching. Mass Spectrometry. 2015;4:A0036\u2013A0036. https:\/\/doi.org\/10.5702\/massspectrometry.A0036.","journal-title":"Mass Spectrometry"},{"key":"3899_CR16","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s13361-018-2111-y","volume":"30","author":"C Ancillotti","year":"2019","unstructured":"Ancillotti C, Ulaszewska M, Mattivi F, Del Bubba M. Untargeted metabolomics analytical strategy based on liquid chromatography\/electrospray ionization linear ion trap quadrupole\/orbitrap mass spectrometry for discovering new polyphenol metabolites in human biofluids after acute ingestion of Vaccinium myrtillus berry supplement. J Am Soc Mass Spectrom. 2019;30:381\u2013402. https:\/\/doi.org\/10.1007\/s13361-018-2111-y.","journal-title":"J Am Soc Mass Spectrom"},{"key":"3899_CR17","doi-asserted-by":"publisher","first-page":"7771","DOI":"10.1007\/s00216-019-02166-6","volume":"411","author":"R Bloch","year":"2019","unstructured":"Bloch R, Sch\u00fctze S-E, M\u00fcller E, R\u00f6der S, Lehmann I, Brack W, Krauss M. Non-targeted mercapturic acid screening in urine using LC-MS\/MS with matrix effect compensation by postcolumn infusion of internal standard (PCI-IS). Anal Bioanal Chem. 2019;411:7771\u201381. https:\/\/doi.org\/10.1007\/s00216-019-02166-6.","journal-title":"Anal Bioanal Chem"},{"key":"3899_CR18","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/BF00321768","volume":"340","author":"W Stanek","year":"1991","unstructured":"Stanek W, Hayek EWH, Krenmayr P, Schmid ER. Tandem mass spectrometric studies of mercapturic acid derivatives. Fresenius J Anal Chem. 1991;340:201\u20136. https:\/\/doi.org\/10.1007\/BF00321768.","journal-title":"Fresenius J Anal Chem"},{"key":"3899_CR19","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1002\/rcm.1071","volume":"17","author":"Z Yan","year":"2003","unstructured":"Yan Z, Caldwell GW, Jones WJ, Masucci JA. Cone voltage induced in-source dissociation of glucuronides in electrospray and implications in biological analyses. Rapid Commun Mass Spectrom. 2003;17:1433\u201342. https:\/\/doi.org\/10.1002\/rcm.1071.","journal-title":"Rapid Commun Mass Spectrom"},{"key":"3899_CR20","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1373\/clinchem.2009.138602","volume":"56","author":"M Vogeser","year":"2010","unstructured":"Vogeser M, Seger C. Pitfalls associated with the use of liquid chromatography\u2013tandem mass spectrometry in the clinical laboratory. Clin Chem. 2010;56:1234\u201344. https:\/\/doi.org\/10.1373\/clinchem.2009.138602.","journal-title":"Clin Chem"},{"key":"3899_CR21","volume-title":"Wiley registry of tandem mass spectral data","author":"HM Oberacher","year":"2011","unstructured":"Oberacher HM. Wiley registry of tandem mass spectral data. Hoboken, New Jersey: John Wiley; 2011."},{"key":"3899_CR22","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.forsciint.2009.12.019","volume":"197","author":"M Pavlic","year":"2010","unstructured":"Pavlic M, Schubert B, Libiseller K, Oberacher H. Comprehensive identification of active compounds in tablets by flow-injection data-dependent tandem mass spectrometry combined with library search. Forensic Sci Int. 2010;197:40\u20137. https:\/\/doi.org\/10.1016\/j.forsciint.2009.12.019.","journal-title":"Forensic Sci Int"},{"key":"3899_CR23","doi-asserted-by":"publisher","first-page":"9149","DOI":"10.1021\/acs.analchem.1c00972","volume":"93","author":"C Huber","year":"2021","unstructured":"Huber C, M\u00fcller E, Schulze T, Brack W, Krauss M. Improving the screening analysis of pesticide metabolites in human biomonitoring by combining high-throughput in vitro incubation and automated LC\u2013HRMS data processing. Anal Chem. 2021;93:9149\u201357. https:\/\/doi.org\/10.1021\/acs.analchem.1c00972.","journal-title":"Anal Chem"},{"key":"3899_CR24","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1159\/000487500","volume":"43","author":"S Eder","year":"2018","unstructured":"Eder S, Leierer J, Kerschbaum J, Rosivall L, Wiecek A, de Zeeuw D, Mark PB, Heinze G, Rossing P, Heerspink HL, Mayer G. A Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers (PROVALID) \u2013 study design and baseline characteristics. KBR. 2018;43:181\u201390. https:\/\/doi.org\/10.1159\/000487500.","journal-title":"KBR"},{"key":"3899_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.envadv.2021.100045","volume":"4","author":"R Hornek-Gausterer","year":"2021","unstructured":"Hornek-Gausterer R, Oberacher H, Reinstadler V, Hartmann C, Liebmann B, Lomako I, Scharf S, Posautz A, K\u00fcbber-Heiss A. A preliminary study on the detection of potential contaminants in the European brown hare (Lepus europaeus) by suspect and microplastics screening. Environmental Advances. 2021;4: 100045. https:\/\/doi.org\/10.1016\/j.envadv.2021.100045.","journal-title":"Environmental Advances"},{"key":"3899_CR26","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.1093\/bioinformatics\/btn323","volume":"24","author":"D Kessner","year":"2008","unstructured":"Kessner D, Chambers M, Burke R, Agus D, Mallick P. ProteoWizard: open source software for rapid proteomics tools development. Bioinformatics. 2008;24:2534\u20136. https:\/\/doi.org\/10.1093\/bioinformatics\/btn323.","journal-title":"Bioinformatics"},{"key":"3899_CR27","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1002\/jms.3185","volume":"48","author":"H Oberacher","year":"2013","unstructured":"Oberacher H, Whitley G, Berger B, Weinmann W. Testing an alternative search algorithm for compound identification with the \u2018Wiley Registry of Tandem Mass Spectral Data, MSforID.\u2019 J Mass Spectrom. 2013;48:497\u2013504. https:\/\/doi.org\/10.1002\/jms.3185.","journal-title":"J Mass Spectrom"},{"key":"3899_CR28","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s00216-018-1504-x","volume":"411","author":"V Reinstadler","year":"2019","unstructured":"Reinstadler V, Lierheimer S, Boettcher M, Oberacher H. A validated workflow for drug detection in oral fluid by non-targeted liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2019;411:867\u201376. https:\/\/doi.org\/10.1007\/s00216-018-1504-x.","journal-title":"Anal Bioanal Chem"},{"key":"3899_CR29","doi-asserted-by":"publisher","first-page":"11721","DOI":"10.1021\/acs.analchem.5b02794","volume":"87","author":"AM Wolfer","year":"2015","unstructured":"Wolfer AM, Gaudin M, Taylor-Robinson SD, Holmes E, Nicholson JK. Development and validation of a high-throughput ultrahigh-performance liquid chromatography\u2013mass spectrometry approach for screening of oxylipins and their precursors. Anal Chem. 2015;87:11721\u201331. https:\/\/doi.org\/10.1021\/acs.analchem.5b02794.","journal-title":"Anal Chem"},{"key":"3899_CR30","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/s41592-019-0344-8","volume":"16","author":"K D\u00fchrkop","year":"2019","unstructured":"D\u00fchrkop K, Fleischauer M, Ludwig M, Aksenov AA, Melnik AV, Meusel M, Dorrestein PC, Rousu J, B\u00f6cker S. SIRIUS 4: a rapid tool for turning tandem mass spectra into metabolite structure information. Nat Methods. 2019;16:299\u2013302. https:\/\/doi.org\/10.1038\/s41592-019-0344-8.","journal-title":"Nat Methods"},{"key":"3899_CR31","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1021\/acs.jproteome.0c00313","volume":"20","author":"L Gatto","year":"2021","unstructured":"Gatto L, Gibb S, Rainer J. MSnbase, efficient and elegant R-based processing and visualization of raw mass spectrometry data. J Proteome Res. 2021;20:1063\u20139. https:\/\/doi.org\/10.1021\/acs.jproteome.0c00313.","journal-title":"J Proteome Res"},{"key":"3899_CR32","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12302-020-00314-9","volume":"32","author":"H Oberacher","year":"2020","unstructured":"Oberacher H, Sasse M, Antignac J-P, Guitton Y, Debrauwer L, Jamin EL, Schulze T, Krauss M, Covaci A, Caballero-Casero N, Rousseau K, Damont A, Fenaille F, Lamoree M, Schymanski EL. A European proposal for quality control and quality assurance of tandem mass spectral libraries. Environ Sci Eur. 2020;32:43. https:\/\/doi.org\/10.1186\/s12302-020-00314-9.","journal-title":"Environ Sci Eur"},{"key":"3899_CR33","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1002\/jms.1777","volume":"45","author":"H Horai","year":"2010","unstructured":"Horai H, Arita M, Kanaya S, Nihei Y, Ikeda T, Suwa K, Ojima Y, Tanaka K, Tanaka S, Aoshima K, Oda Y, Kakazu Y, Kusano M, Tohge T, Matsuda F, Sawada Y, Hirai MY, Nakanishi H, Ikeda K, Akimoto N, Maoka T, Takahashi H, Ara T, Sakurai N, Suzuki H, Shibata D, Neumann S, Iida T, Tanaka K, Funatsu K, Matsuura F, Soga T, Taguchi R, Saito K, Nishioka T. MassBank: a public repository for sharing mass spectral data for life sciences. J Mass Spectrom. 2010;45:703\u201314. https:\/\/doi.org\/10.1002\/jms.1777.","journal-title":"J Mass Spectrom"},{"key":"3899_CR34","doi-asserted-by":"publisher","DOI":"10.1201\/b14488","volume-title":"Drug metabolism: chemical and enzymatic aspects","author":"JP Uetrecht","year":"2007","unstructured":"Uetrecht JP, Trager W. Drug metabolism: chemical and enzymatic aspects. Boca Raton: CRC Press; 2007."},{"key":"3899_CR35","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jpba.2017.01.054","volume":"144","author":"CP Vieira","year":"2017","unstructured":"Vieira CP, Neves DV, Cesarino EJ, Rocha A, Poirier S, Lanchote VL. An indirect stereoselective analysis of nebivolol glucuronides in plasma by LC-MS\/MS: application to clinical pharmacokinetics. J Pharm Biomed Anal. 2017;144:25\u201330. https:\/\/doi.org\/10.1016\/j.jpba.2017.01.054.","journal-title":"J Pharm Biomed Anal"}],"container-title":["Analytical and Bioanalytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00216-022-03899-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00216-022-03899-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00216-022-03899-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T18:05:08Z","timestamp":1646157908000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00216-022-03899-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":35,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["3899"],"URL":"https:\/\/doi.org\/10.1007\/s00216-022-03899-7","relation":{},"ISSN":["1618-2642","1618-2650"],"issn-type":[{"value":"1618-2642","type":"print"},{"value":"1618-2650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,26]]},"assertion":[{"value":"27 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The PROVALID study protocol was approved in each participating country by the responsible local IRB. The analysis of drugs and drug metabolites in urine samples (PROVALID adherence) was further approved by the ethics committee of Innsbruck Medical University (EK Nr. 1235\/2019).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}