{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:54:14Z","timestamp":1792457654758,"version":"4.5.0"},"reference-count":16,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[1999,10,1]],"date-time":"1999-10-01T00:00:00Z","timestamp":938736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Appl Thromb Hemost"],"published-print":{"date-parts":[[1999,10]]},"abstract":"<jats:p>\n                    Argatroban is a peptidomimetic inhibitor of throm bin that is currently undergoing extensive clinical trials as a heparin substitute for thrombotic complications. Argatroban is readily metabolized into a major derivative, M1, that has phar macological characteristics distinct from its parent compound. The currently available clot-based assays measure the cumula tive anticoagulant effect of argatroban and its metabolite(s). Available HPLC methods do not differentiate between argatro ban and M1-metabolite. A modified method was developed to simultaneously quantitate M1-metabolite and argatroban in biological fluids. Initial validation studies for the method in cluded clinical trials of argatroban in patients with heparin- induced thrombocytopenia, (ARG 911 Study) and coronary in terventional procedures (ARG 310 Study). Plasma samples were extracted with acetonitrile and reconstituted in a mobile phase. Calibration curves were prepared by running known standards of argatroban and M1-metabolite in normal human plasma. Ultraviolet detection was made at 320 nm. The reten tion times for argatroban and M1-metabolite peaks were found to be 10.5 \u00b1 0.3 minutes and 3.9 \u00b1 0.1 minutes, respectively. The extraction efficiency was &gt; 95% (r\n                    <jats:sup>2<\/jats:sup>\n                    = 0.99). In heparin- induced thrombocytopenia patients with major bleeding com plications (n = 30), the relative increase in M1-metabolite compared to argatroban varied widely (two- to eight-fold). The mean concentration of argatroban during the steady infusion period was found to be 0.7 \u00b1 0.35 \u03bcg\/mL, and for M1- metabolite, it was 5.5 \u00b1 2.8 \u03bcg\/mL. Proportionate results were not seen when higher dosages of argatroban were administered (coronary angioplasty studies). Argatroban and M1-metabolite levels also compared well with the results in global clotting assays. Owing to the simultaneous quantitation of argatroban and M1-metabolite, this method provides a rapid assessment of the pharmacokinetics and pharmacodynamics of argatroban. The differential quantitation may be useful in the assessment of relative metabolic turnover of argatroban that can be related to the hepatic and renal functions in a given patient.\n                  <\/jats:p>","DOI":"10.1177\/107602969900500409","type":"journal-article","created":{"date-parts":[[2007,11,26]],"date-time":"2007-11-26T17:47:05Z","timestamp":1196099225000},"page":"252-258","source":"Crossref","is-referenced-by-count":19,"title":["Simultaneous Monitoring of Argatroban and Its Major Metabolite Using an HPLC Method: Potential Clinical Applications"],"prefix":"10.1177","volume":"5","author":[{"given":"Sarfraz","family":"Ahmad","sequence":"first","affiliation":[{"name":"Departments of Pathology and Pharmacology, and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pharmacology, and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"George","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pharmacology, and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pharmacology, and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter P.","family":"Jeske","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pharmacology, and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajalaxmi","family":"McKenna","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pharmacology, and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce E.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pharmacology, and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanine M.","family":"Walenga","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pharmacology, and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawed","family":"Fareed","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Pharmacology, and Cardiovascular Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[1999,10,1]]},"reference":[{"issue":"1","key":"atypb1","first-page":"22","volume":"36","author":"Walenga JM","year":"1999","journal-title":"Semin Hematol"},{"key":"atypb2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1023\/A:1008872031770","volume":"5","author":"Jang IK","year":"1998","journal-title":"J Thromb Thrombolysis"},{"key":"atypb3","first-page":"364","volume":"122","author":"Weitz JI","year":"1993","journal-title":"J Lab Clin Med"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-996091"},{"key":"atypb5","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1648875"},{"key":"atypb6","doi-asserted-by":"publisher","DOI":"10.1177\/107602969800400405"},{"key":"atypb7","doi-asserted-by":"publisher","DOI":"10.1097\/00019501-199606000-00008"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)54894-8"},{"key":"atypb9","unstructured":"Data on file, Texas Biotechnology Corporation, Houston, TX."},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(81)91279-1"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1000393"},{"key":"atypb12","first-page":"A67","volume":"78","author":"Ahmad S.","year":"1999","journal-title":"Ann Hematol"},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.87.5.1622"},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(95)80007-F"},{"key":"atypb15","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.8.5.625"},{"key":"atypb16","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.83.5.1510"}],"container-title":["Clinical and Applied Thrombosis\/Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/107602969900500409","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/107602969900500409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:06:39Z","timestamp":1777385199000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/107602969900500409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,10]]},"references-count":16,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1999,10]]}},"alternative-id":["10.1177\/107602969900500409"],"URL":"https:\/\/doi.org\/10.1177\/107602969900500409","relation":{},"ISSN":["1076-0296","1938-2723"],"issn-type":[{"value":"1076-0296","type":"print"},{"value":"1938-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,10]]}}}