{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:45:06Z","timestamp":1789731906431,"version":"4.0.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973387"],"award-info":[{"award-number":["81973387"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Therapeutic drug monitoring (TDM) of immunosuppressive drugs (ISDs) is essential for transplant recipients. The aim of this study is to establish an LC\u2013MS\/MS method to determine mycophenolic acid (MPA) and its metabolite, cyclosporin A (CsA), tacrolimus (TAC) and sirolimus (SRL) levels in whole blood and plasma simultaneously. Whole blood and plasma samples were treated with protein precipitation. After centrifugation, the supernatant was eluted through Agilent Eclipse XDB-C18 (3.5\u00a0\u03bcm, 2.1\u00a0mm\u2009\u00d7\u2009100\u00a0mm) column by water (2\u00a0mmol\/L ammonium formate) and methanol through a gradient method. The ISDs in renal allograft recipients were compared with TDM results. The methods established were linear within a range of 0.204\u201351\u00a0\u03bcg\/mL for MPA, 2.0\u2013500\u00a0\u03bcg\/mL for MPAG, 4\u20131,000\u00a0ng\/mL for CsA, 0.2\u201350\u00a0ng\/mL for TAC and 0.2\u201350\u00a0ng\/mL for SRL (r2\u2009=\u20090.9998) in plasma and whole blood. The intra- and inter-day accuracy was in the range of 85\u2013115%, and imprecision of all ISDs was\u2009&amp;lt;15%. Plasma MPA and MPAG levels can be estimated based on whole blood level: Cplasma\u2009=\u20091.52\u2009\u00d7\u2009Cblood\u2009+\u20090.16 (r2\u2009=\u20090.9168) and Cplasma\u2009=\u20091.58\u2009\u00d7\u2009Cblood \u2212 0.56 (r2\u2009=\u20090.9069). The CsA (r2\u2009=\u20090.9694, n\u2009=\u200960), TAC (r2\u2009=\u20090.9426, n\u2009=\u2009115) and SRL (r2\u2009=\u20090.9484, n\u2009=\u200970) levels in whole blood were consistent with those obtained from the immunoassays. The LC\u2013MS\/MS method established is suitable for patients with various immunosuppressive regimens.<\/jats:p>","DOI":"10.1093\/chromsci\/bmaf037","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T02:59:02Z","timestamp":1750820342000},"source":"Crossref","is-referenced-by-count":1,"title":["Simultaneous Measurement of Mycophenolic Acid with Other Immunosuppressants in Whole Blood and Plasma by Using Liquid Chromatography\u2013Tandem Mass Spectrometry"],"prefix":"10.1093","volume":"63","author":[{"given":"Yu-Ping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine , 197 Ruijin Er Road, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hui","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine , 197 Ruijin Er Road, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Han","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine , 197 Ruijin Er Road, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Shao","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine , 197 Ruijin Er Road, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Jun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine , 197 Ruijin Er Road, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Qiang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine , 197 Ruijin Er Road, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine , 197 Ruijin Er Road, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"issue":"6","key":"2025071411013260300_ref1","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/j.jceh.2022.06.007","article-title":"Immunosuppressive drugs in liver transplant: An insight","volume":"12","author":"Panackel","year":"2022","journal-title":"Journal of Clinical and Experimental Hepatology"},{"key":"2025071411013260300_ref2","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1002\/dta.2290","article-title":"Recent advances in analytical methods for the therapeutic drug monitoring of immunosuppressive drugs","volume":"10","author":"Zhang","year":"2018","journal-title":"Drug Testing and Analysis"},{"key":"2025071411013260300_ref3","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1515\/CCLM.2004.242","article-title":"Therapeutic monitoring of immunosuppressant drugs. Where are we?","volume":"42","author":"Wallemacq","year":"2004","journal-title":"Clinical Chemistry and Laboratory Medicine"},{"key":"2025071411013260300_ref4","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1093\/clinchem\/40.12.2247","article-title":"Plasma vs whole blood for therapeutic drug monitoring of patients receiving FK 506 for immunosuppression","volume":"40","author":"Winkler","year":"1994","journal-title":"Clinical Chemistry"},{"key":"2025071411013260300_ref5","first-page":"105","article-title":"Interferences in immunoassay","volume":"25","author":"Tate","year":"2004","journal-title":"Clinical Biochemist Reviews"},{"key":"2025071411013260300_ref6","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1177\/039463200802100311","article-title":"Quantification of sirolimus and everolimus by immunoassay techniques: Test specificity and cross-reactivity evaluation","volume":"21","author":"Pieri","year":"2008","journal-title":"International Journal of Immunopathology and Pharmacology"},{"key":"2025071411013260300_ref7","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.jchromb.2004.02.040","article-title":"Simultaneous determination of four immunosuppressants by means of high speed and robust on-line solid phase extraction\u2013high performance liquid chromatography\u2013tandem mass spectrometry","volume":"805","author":"Koal","year":"2004","journal-title":"Journal of Chromatography B"},{"key":"2025071411013260300_ref8","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1097\/FTD.0b013e318192304c","article-title":"Robust, high-throughput LC-MS\/MS method for therapeutic drug monitoring of cyclosporine, tacrolimus, everolimus, and sirolimus in whole blood","volume":"31","author":"Koster","year":"2009","journal-title":"Therapeutic Drug Monitoring"},{"key":"2025071411013260300_ref9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jchromb.2013.03.014","article-title":"Two rapid ultra performance liquid chromatography\/tandem mass spectrometry (UPLC\/MS\/MS) methods with common sample pretreatment for therapeutic drug monitoring of immunosuppressants compared to immunoassay","volume":"928","author":"Tszyrsznic","year":"2013","journal-title":"Journal of Chromatography B"},{"issue":"1\u20132","key":"2025071411013260300_ref10","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.cca.2006.05.019","article-title":"Inclusion of MPA and in a rapid multi-drug LC\u2013tandem mass spectrometric method for simultaneous determination of immunosuppressants","volume":"373","author":"Ceglarek","year":"2006","journal-title":"Clinica Chimica Acta"},{"key":"2025071411013260300_ref11","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1007\/s40262-019-00854-1","article-title":"Unbound plasma, total plasma, and whole-blood tacrolimus pharmacokinetics early after thoracic organ transplantation","volume":"59","author":"Sikma","year":"2019","journal-title":"Clinical Pharmacokinetics"},{"key":"2025071411013260300_ref12","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.chroma.2018.03.010","article-title":"A simple and highly sensitive on-line column extraction liquid chromatography-tandem mass spectrometry method for the determination of protein-unbound tacrolimus in human plasma samples","volume":"1547","author":"Bittersohl","year":"2018","journal-title":"Journal of Chromatography. A"},{"key":"2025071411013260300_ref13","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.jchromb.2013.01.017","article-title":"Simultaneous online SPE\u2013HPLC\u2013MS\/MS analysis of docetaxel, temsirolimus and sirolimus in whole blood and human plasma","volume":"921-922","author":"Navarrete","year":"2013","journal-title":"Journal of Chromatography B"},{"issue":"16","key":"2025071411013260300_ref14","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.4155\/bio-2019-0143","article-title":"A multidrug LC-MS\/MS method for the determination of five immunosuppressants in oral fluid","volume":"11","author":"Paniagua-Gonz\u00e1lez","year":"2019","journal-title":"Bioanalysis"},{"key":"2025071411013260300_ref15","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.clinbiochem.2019.11.006","article-title":"An isotope dilution LC-MS\/MS based candidate reference method for the quantification of cyclosporine a, tacrolimus, sirolimus and everolimus in human whole blood","volume":"82","author":"Taibon","year":"2020","journal-title":"Clinical Biochemistry"},{"issue":"5","key":"2025071411013260300_ref16","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1515\/cclm-2017-0583","article-title":"Measurement of sirolimus concentrations in human blood using an automated electrochemiluminescence immunoassay (ECLIA): A multicenter evaluation","volume":"56","author":"Stove","year":"2018","journal-title":"Clinical Chemistry and Laboratory Medicine"},{"key":"2025071411013260300_ref17","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1373\/clinchem.2011.167189","article-title":"Liquid chromatography-tandem mass spectrometry or automated immunoassays: What are the future trends in therapeutic drug monitoring?","volume":"58","author":"Brandhorst","year":"2012","journal-title":"Clinical Chemistry"},{"key":"2025071411013260300_ref18","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1093\/clinchem\/46.3.365","article-title":"Determination of the acyl glucuronide metabolite of mycophenolic acid in human plasma by HPLC and EMIT","volume":"46","author":"Shipkova","year":"2000","journal-title":"Clinical Chemistry"},{"key":"2025071411013260300_ref19","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1097\/00007691-200112000-00013","article-title":"Analytic validation of the enzyme multiplied immunoassay technique for the determination of mycophenolic acid in plasma from renal transplant recipients compared with a high-performance liquid chromatographic assay","volume":"23","author":"Hosotsubo","year":"2001","journal-title":"Therapeutic Drug Monitoring"},{"key":"2025071411013260300_ref20","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/S0041-1345(98)01936-8","article-title":"Overestimation of mycophenolic acid by EMIT correlates with MPA metabolite","volume":"31","author":"Shipkova","year":"1999","journal-title":"Transplantation Proceedings"},{"key":"2025071411013260300_ref21","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1080\/00032710701583466","article-title":"Determination of mycophenolic acid (MPA) and its acyl and phenol glucuronide metabolits simultaneously in human plasma by a simplified HPLC method","volume":"40","author":"Chen","year":"2007","journal-title":"Analytical Letters"},{"key":"2025071411013260300_ref22","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1097\/FTD.0b013e3181f01397","article-title":"Establishment of high-performance liquid chromatography and enzyme multiplied immunoassay technology methods for determination of free mycophenolic acid and its application in Chinese liver transplant recipients","volume":"32","author":"Chen","year":"2010","journal-title":"Therapeutic Drug Monitoring"},{"issue":"3","key":"2025071411013260300_ref23","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1097\/FTD.0000000000000392","article-title":"Simultaneous determination of protein-unbound cyclosporine a and mycophenolic acid in kidney transplant patients using liquid chromatography-tandem mass spectrometry","volume":"39","author":"Bittersohl","year":"2017","journal-title":"Therapeutic Drug Monitoring"},{"key":"2025071411013260300_ref24","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1208\/s12248-013-9500-8","article-title":"Population pharmacokinetics of cyclosporine in transplant recipients","volume":"15","author":"Han","year":"2013","journal-title":"The AAPS Journal"},{"key":"2025071411013260300_ref25","doi-asserted-by":"publisher","first-page":"374","DOI":"10.2215\/CJN.03791106","article-title":"Therapeutic monitoring of calcineurin inhibitors for the nephrologist","volume":"2","author":"Schiff","year":"2007","journal-title":"Clinical Journal of the American Society of Nephrology"},{"key":"2025071411013260300_ref26","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1097\/00007691-200002000-00006","article-title":"Pharmacokinetics and metabolism of sirolimus","volume":"22","author":"Gallant-Haidner","year":"2000","journal-title":"Therapeutic Drug Monitoring"},{"key":"2025071411013260300_ref27","first-page":"2753","article-title":"Effect of temperature and hematocrit on plasma concentration of FK 506","volume":"23","author":"Machida","year":"1991","journal-title":"Transplantation Proceedings"}],"container-title":["Journal of Chromatographic Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/chromsci\/article-pdf\/63\/6\/bmaf037\/63573609\/bmaf037.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/chromsci\/article-pdf\/63\/6\/bmaf037\/63573609\/bmaf037.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T15:01:40Z","timestamp":1752505300000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/chromsci\/article\/doi\/10.1093\/chromsci\/bmaf037\/8173255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6,10]]}},"URL":"https:\/\/doi.org\/10.1093\/chromsci\/bmaf037","relation":{},"ISSN":["0021-9665","1945-239X"],"issn-type":[{"value":"0021-9665","type":"print"},{"value":"1945-239X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,6,10]]},"article-number":"bmaf037"}}