title: An ultra performance liquid chromatography-tandem mass spectrometry method for the therapeutic drug monitoring of isavuconazole and seven other antifungal compounds in plasma samples.
abstract: A new analytical method was developed for the routine Therapeutic Drug Monitoring of 8 antifungals compounds in 50μL of plasma: isavuconazole (ISZ), voriconazole (VRZ), posaconazole (PSZ), fluconazole (FCZ), caspofungin (CSF), flucytosine (5FC), itraconazole (ITZ) and its metabolite OH-itraconazole (OH-ITZ). After adding 50μL of the internal standard, which consisted in a mixture of the deuterated isotopes of the quantified compounds, the sample treatment consisted in a simple protein precipitation with 400μL of acetonitrile. Five microliters of the supernatant were directly injected into the chromatographic system. The chromatographic separation was performed with a Waters C18-BEH column and a mobile phase consisting in a mixture of water and acetonitrile, both containing 0.1% of formic acid. The total run time was 3min and the detection of the analytes was performed by electrospray ionization in a positive mode using selected reaction monitoring. Intra and inter-day precision and inaccuracy were <15% over the calibration ranges that were determined according to their clinical relevance: 0.20-20.0mg/L for ISZ, VRZ, PSZ, ITZ, and OH-ITZ; 0.50-50.0mg/L for FCZ and CSF; 2.00-200mg/L for 5FC. This simple and fast method was found suitable for routine therapeutic drug monitoring.
authors.affiliation: Service de pharmacologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: Balthazar
authors.initials: B
authors.lastname: Toussaint
authors.affiliation: Service des maladies infectieuses et tropicales, Centre d'infectiologie Necker-Pasteur, Paris, France; Institut Pasteur, Centre National de Référence Mycoses invasives et Antifongiques, Paris, France; Institut Pasteur, Unité de Mycologie Moléculaire, CNRS URA3012, Paris, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Lanternier
authors.affiliation: Service de pharmacologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Woloch
authors.affiliation: Service de pharmacologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Fournier
authors.affiliation: Service de pharmacologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Launay
authors.affiliation: Service de pharmacologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Billaud
authors.affiliation: Université Paris-Descartes; Faculté de Médecine; Unité de Parasitologie-Mycologie, Service de Microbiologie, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Dannaoui
authors.affiliation: Service des maladies infectieuses et tropicales, Centre d'infectiologie Necker-Pasteur, Paris, France; Institut Pasteur, Centre National de Référence Mycoses invasives et Antifongiques, Paris, France; Institut Pasteur, Unité de Mycologie Moléculaire, CNRS URA3012, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: Service de pharmacologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France; INSERM U1129, Hôpital Necker, Université Paris-Descartes, Paris, France. Electronic address: vincent.jullien@aphp.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
mesh_terms: D000935:Antifungal Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D016014:Linear Models; D009570:Nitriles / Q000097:blood*; D011725:Pyridines / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014230:Triazoles / Q000097:blood*
chemical_list: D000935:Antifungal Agents; D009570:Nitriles; D011725:Pyridines; D014230:Triazoles; C508735:isavuconazole
keywords: Antifungal drugs; Liquid chromatography; Tandem mass spectrometry; Therapeutic drug monitoring