{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:44:21Z","timestamp":1791607461387,"version":"4.3.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Monitoring of medication compliance and drug abuse is used by clinicians to increase patient prescription drug compliance and reduce illicit drug abuse and diversion. Despite available immunoassays, chromatography-mass spectrometry\u2013based methods are considered the gold standard for urine drug monitoring owing to higher sensitivities and specificities. Herein, we report a fast, convenient ultraperformance liquid chromatography\u2013tandem mass spectrometry (UPLC-MS\/MS) assay to detect or quantify 37 clinically relevant prescription drugs, drugs of abuse, and related glucuronides and other metabolites in human urine by single diluted sample injection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Analytes consisted of prescription and illicit opioids, benzodiazepines, and drugs of abuse, including parent compounds and glucuronidated and nonglucuronidated metabolites. Urine samples were diluted with water and supplemented with deuterated internal standards without enzymatic hydrolysis, analyte extraction, or sample purification. Analytes were separated by reversed-phase UPLC and quantified by positive-mode electrospray ionization and collision-induced dissociation MS. Assay validation followed Food and Drug Administration bioanalytical guidelines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Total analytical run time was 5.5 min. All analytes demonstrated acceptable inter- and intraassay accuracy, imprecision, and linearity throughout clinically relevant analytical ranges (1\u20132000 ng\/mL, depending on analyte). All analytes demonstrated acceptable selectivity, stability, matrix effects, carryover, and performance compared to national reference laboratory or previously validated in-house methods. A total of 23 and 14 analytes were validated for quantitative and qualitative testing, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A convenient UPLC-MS\/MS assay for simultaneously monitoring 37 analytes in human urine was validated for use in pain management testing. Advantages of this multiplex assay include facile sample preparation and higher-throughput definitive detection including glucuronide metabolite quantification.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1373\/jalm.2018.027342","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T23:02:59Z","timestamp":1548198179000},"page":"974-992","source":"Crossref","is-referenced-by-count":24,"title":["A Rapid Dilute-and-Shoot UPLC-MS\/MS Assay to Simultaneously Measure 37 Drugs and Related Metabolites in Human Urine for Use in Clinical Pain Management"],"prefix":"10.1093","volume":"3","author":[{"given":"Jayme L","family":"Dahlin","sequence":"first","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Palte","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"LaMacchia","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena K","family":"Petrides","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Boston, MA"},{"name":"Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,1]]},"reference":[{"key":"2022020118541655800_B1","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1093\/jat\/32.8.530","article-title":"Urine drug testing of chronic pain patients: licit and illicit drug patterns","volume":"32","author":"Cone","year":"2008","journal-title":"J Anal Toxicol"},{"key":"2022020118541655800_B2","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s11606-014-3010-y","article-title":"Chronic opioid therapy urine drug testing in primary care: prevalence and predictors of aberrant results","volume":"29","author":"Turner","year":"2014","journal-title":"J Gen Intern Med"},{"key":"2022020118541655800_B3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/AJP.0b013e31802b4f95","article-title":"Urine toxicology screening among chronic pain patients on opioid therapy: frequency and predictability of abnormal findings","volume":"23","author":"Michna","year":"2007","journal-title":"Clin J Pain"},{"key":"2022020118541655800_B4","first-page":"123","article-title":"Does random urine drug testing reduce illicit drug use in chronic pain patients receiving opioids?","volume":"9","author":"Manchikanti","year":"2006","journal-title":"Pain Physician"},{"key":"2022020118541655800_B5","first-page":"ES119","article-title":"Urine drug testing: current recommendations and best practices","volume":"15","author":"Owen","year":"2012","journal-title":"Pain Physician"},{"key":"2022020118541655800_B6","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/pm\/pnx285","article-title":"Rational urine drug monitoring in patients receiving opioids for chronic pain: consensus recommendations","volume":"19","author":"Argoff","year":"2018","journal-title":"Pain Med"},{"key":"2022020118541655800_B7","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1309\/AJCPMJKBC6VJA1SP","article-title":"A hybrid approach to urine drug testing using high-resolution mass spectrometry and select immunoassays","volume":"143","author":"McMillin","year":"2015","journal-title":"Am J Clin Pathol"},{"key":"2022020118541655800_B8","doi-asserted-by":"crossref","first-page":"71","DOI":"10.36076\/ppj.2010\/13\/71","article-title":"Comparison of clonazepam compliance by measurement of urinary concentration by immunoassay and LC-MS\/MS in pain management population","volume":"13","author":"West","year":"2010","journal-title":"Pain Physician"},{"key":"2022020118541655800_B9","first-page":"359","article-title":"KIMS, CEDIA, and HS-CEDIA immunoassays are inadequately sensitive for detection of benzodiazepines in urine from patients treated for chronic pain","volume":"17","author":"Darragh","year":"2014","journal-title":"Pain Physician"},{"key":"2022020118541655800_B10","doi-asserted-by":"crossref","first-page":"259","DOI":"10.36076\/ppj.2011\/14\/259","article-title":"Comparative evaluation of the accuracy of benzodiazepine testing in chronic pain patients utilizing immunoassay with liquid chromatography tandem mass spectrometry (LC\/MS\/MS) of urine drug testing","volume":"14","author":"Manchikanti","year":"2011","journal-title":"Pain Physician"},{"key":"2022020118541655800_B11","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1111\/pme.12207","article-title":"Optimizing urine drug testing for monitoring medication compliance in pain management","volume":"14","author":"Melanson","year":"2013","journal-title":"Pain Med"},{"key":"2022020118541655800_B12","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.cca.2012.03.017","article-title":"Therapeutic monitoring of benzodiazepines in the management of pain: current limitations of point of care immunoassays suggest testing by mass spectrometry to assure accuracy and improve patient safety","volume":"413","author":"Mikel","year":"2012","journal-title":"Clin Chem Acta"},{"key":"2022020118541655800_B13","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/pme.12265","article-title":"The clinical impact of a false-positive urine cocaine screening result on a patient's pain management","volume":"16","author":"Kim","year":"2015","journal-title":"Pain Med"},{"key":"2022020118541655800_B14","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.kjms.2016.01.007","article-title":"Simultaneous identification of abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry","volume":"32","author":"Lee","year":"2016","journal-title":"Kaohsiung J Med Sci"},{"key":"2022020118541655800_B15","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.clinbiochem.2013.03.027","article-title":"Simultaneous detection of 19 drugs of abuse on dried urine spot by liquid chromatography-tandem mass spectrometry","volume":"46","author":"Lee","year":"2013","journal-title":"Clin Biochem"},{"key":"2022020118541655800_B16","doi-asserted-by":"crossref","first-page":"158","DOI":"10.9758\/cpn.2013.11.3.158","article-title":"Simultaneous screening of 177 drugs of abuse in urine using ultra-performance liquid chromatography with tandem mass spectrometry in drug-intoxicated patients","volume":"11","author":"Lee","year":"2013","journal-title":"Clin Psychopharmacol Neurosci"},{"key":"2022020118541655800_B17","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/jat\/bkv024","article-title":"Simultaneous quantitation of 78 drugs and metabolites in urine with a dilute-and-shoot LC-MS-MS assay","volume":"39","author":"Cao","year":"2015","journal-title":"J Anal Toxicol"},{"key":"2022020118541655800_B18","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jchromb.2014.08.033","article-title":"Simultaneous detection of 93 conventional and emerging drugs of abuse and their metabolites in urine by UHPLC-MS\/MS","volume":"969","author":"Tang","year":"2014","journal-title":"J Chromatogr B"},{"key":"2022020118541655800_B19","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1007\/s12272-013-0225-0","article-title":"Screening of multiple drugs of abuse and metabolites in urine using LC\/MS\/MS with polarity switching electrospray ionization","volume":"37","author":"Shin","year":"2014","journal-title":"Arch Pharm Res"},{"key":"2022020118541655800_B20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jchromb.2013.12.014","article-title":"Screening and quantitative determination of drugs of abuse in diluted urine by UPLC-MS\/MS","volume":"947\u2013948","author":"Hegstad","year":"2014","journal-title":"J Chromatogr B"},{"key":"2022020118541655800_B21","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/bmc.2945","article-title":"Rapid and simultaneous determination of multiple classes of abused drugs and metabolites in human urine by a robust LC-MS\/MS method\u2014application to urine drug testing in pain clinics","volume":"27","author":"Wang","year":"2013","journal-title":"Biomed Chromatogr"},{"key":"2022020118541655800_B22","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/jat\/bks071","article-title":"Evaluation of high-resolution mass spectrometry for urine toxicology screening in a pain management setting","volume":"36","author":"Crews","year":"2012","journal-title":"J Anal Toxicol"},{"key":"2022020118541655800_B23","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/j.clinbiochem.2009.07.019","article-title":"Drugs of abuse testing by tandem mass spectrometry: a rapid, simple method to replace immunoassays","volume":"42","author":"Eichhorst","year":"2009","journal-title":"Clin Biochem Rev"},{"key":"2022020118541655800_B24","first-page":"95","article-title":"Simultaneous quantification of 19 drugs\/metabolites in urine important for pain management by liquid chromatography-tandem mass spectrometry","volume":"50","author":"Yuan","year":"2011","journal-title":"Clin Chem Lab Med"},{"key":"2022020118541655800_B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jchromb.2015.06.028","article-title":"Development of a new multi-analyte assay for the simultaneous detection of opioids in serum and other body fluids using liquid chromatography-tandem mass spectrometry","volume":"1001","author":"Eckart","year":"2015","journal-title":"J Chromatogr B"},{"key":"2022020118541655800_B26","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.4155\/bio.11.266","article-title":"Hydrophilic interaction LC-MS\/MS analysis of opioids in urine: significance of glucuronide metabolites","volume":"3","author":"French","year":"2011","journal-title":"Bioanalysis"},{"key":"2022020118541655800_B27","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1093\/jat\/30.8.570","article-title":"Incomplete recovery of prescription opioids in urine using enzymatic hydrolysis of glucuronide metabolites","volume":"30","author":"Wang","year":"2006","journal-title":"J Anal Toxicol"},{"key":"2022020118541655800_B28","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/jat\/bks063","article-title":"Improved detection of opioid use in chronic pain patients through monitoring of opioid glucuronides in urine","volume":"36","author":"Dickerson","year":"2012","journal-title":"J Anal Toxicol"},{"key":"2022020118541655800_B29","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cca.2013.03.010","article-title":"Significant cost savings achieved by in-sourcing urine drug testing for monitoring medication compliance in pain management","volume":"422","author":"Melanson","year":"2013","journal-title":"Clin Chim Acta"},{"key":"2022020118541655800_B30","first-page":"S49","article-title":"Limit of blank, limit of detection and limit of quantitation","volume":"29","author":"Armbruster","year":"2008","journal-title":"Clin Biochem Rev"},{"key":"2022020118541655800_B31","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.clinbiochem.2014.07.018","article-title":"The development and validation of a turbulent flow-liquid chromatography-tandem mass spectrometric method for the simultaneous quantification of citalopram, sertraline, bupropion and hydroxybupropion in serum","volume":"47","author":"Petrides","year":"2014","journal-title":"Clin Biochem"},{"key":"2022020118541655800_B32","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1515\/cclm-2016-0418","article-title":"A rapid UPLC-MS\/MS assay for the simultaneous measurement of fluconazole, voriconazole, posaconazole, itraconazole, and hydroxyitraconazole concentrations in serum","volume":"55","author":"Basu","year":"2017","journal-title":"Clin Chem Lab Med"},{"key":"2022020118541655800_B33","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1021\/ac971078+","article-title":"Matrix effect in quantitative LC\/MS\/MS analyses of biological fluids: a method for determination of finasteride in human plasma at picogram per milliliter concentrations","volume":"70","author":"Matuszewski","year":"1998","journal-title":"Anal Chem"},{"key":"2022020118541655800_B34","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.clinbiochem.2015.05.023","article-title":"The development of a high-performance liquid chromatography-tandem mass spectrometric method for simultaneous quantification of morphine, morphine-3-\u03b2-glucuronide, morphine-6-\u03b2-glucuronide, hydromorphone, and normorphine in serum","volume":"48","author":"Sartori","year":"2015","journal-title":"Clin Biochem"},{"key":"2022020118541655800_B35","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cca.2012.11.020","article-title":"Stability of pain-related medications, metabolites, and illicit substances in urine","volume":"416","author":"Gonzales","year":"2013","journal-title":"Clin Chem Acta"},{"key":"2022020118541655800_B36","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/jat\/bkw084","article-title":"Stability of 26 sedative hypnotics in six toxicological matrices at different storage conditions","volume":"40","author":"Mata","year":"2016","journal-title":"J Anal Toxicol"},{"key":"2022020118541655800_B37","article-title":"Using clinical laboratory tests to monitor drug therapy in pain management patients","author":"Langman","year":"2017"},{"key":"2022020118541655800_B38","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1373\/jalm.2017.023804","article-title":"Use of metabolic ratios of drugs in urine for monitoring pain management patients","volume":"2","author":"Flood","year":"2018","journal-title":"J Appl Lab Med"},{"key":"2022020118541655800_B39","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1093\/jat\/32.7.516","article-title":"Urinary buprenorphine concentrations in patients treated with suboxone as determined by liquid chromatography-mass spectrometry and CEDIA immunoassay","volume":"32","author":"Hull","year":"2008","journal-title":"J Anal Toxicol"}],"container-title":["The Journal of Applied Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/3\/6\/974\/42354101\/3_3_6_974.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/3\/6\/974\/42354101\/3_3_6_974.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T19:06:16Z","timestamp":1643742376000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jalm\/article\/3\/6\/974\/5603099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,1]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,5,1]]},"published-print":{"date-parts":[[2019,5,1]]}},"URL":"https:\/\/doi.org\/10.1373\/jalm.2018.027342","relation":{},"ISSN":["2576-9456","2475-7241"],"issn-type":[{"value":"2576-9456","type":"print"},{"value":"2475-7241","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,5,1]]},"published":{"date-parts":[[2019,5,1]]}}}