{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:15:50Z","timestamp":1790640950186,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS\/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS\/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.<\/jats:p>","DOI":"10.1128\/aac.00281-13","type":"journal-article","created":{"date-parts":[[2013,4,30]],"date-time":"2013-04-30T03:01:41Z","timestamp":1367290901000},"page":"3147-3158","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir"],"prefix":"10.1128","volume":"57","author":[{"given":"Manel","family":"Aouri","sequence":"first","affiliation":[{"name":"Innovation &amp; Development Laboratory, University of Lausanne, Lausanne, Switzerland"},{"name":"Division of Clinical Pharmacology, Service of Biomedicine, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius","family":"Moradpour","sequence":"additional","affiliation":[{"name":"Service of Gastroenterology and Hepatology, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Cavassini","sequence":"additional","affiliation":[{"name":"Service of Infectious Diseases, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mercier","sequence":"additional","affiliation":[{"name":"Innovation &amp; Development Laboratory, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Buclin","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Service of Biomedicine, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Csajka","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Service of Biomedicine, University of Lausanne, Lausanne, Switzerland"},{"name":"School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalio","family":"Telenti","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andri","family":"Rauch","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent A.","family":"Decosterd","sequence":"additional","affiliation":[{"name":"Innovation &amp; Development Laboratory, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.02.023"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032653"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040842"},{"key":"e_1_3_3_5_2","unstructured":"FDA. 2011. 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