title: Cross-validation of a mass spectrometric-based method for the therapeutic drug monitoring of irinotecan: implementation of matrix-assisted laser desorption/ionization mass spectrometry in pharmacokinetic measurements.
abstract: Irinotecan is a widely used antineoplastic drug, mostly employed for the treatment of colorectal cancer. This drug is a feasible candidate for therapeutic drug monitoring due to the presence of a wide inter-individual variability in the pharmacokinetic and pharmacodynamic parameters. In order to determine the drug concentration during the administration protocol, we developed a quantitative MALDI-MS method using CHCA as MALDI matrix. Here, we demonstrate that MALDI-TOF can be applied in a routine setting for therapeutic drug monitoring in humans offering quick and accurate results. To reach this aim, we cross validated, according to FDA and EMA guidelines, the MALDI-TOF method in comparison with a standard LC-MS/MS method, applying it for the quantification of 108 patients' plasma samples from a clinical trial. Standard curves for irinotecan were linear (R (2) ≥ 0.9842) over the concentration ranges between 300 and 10,000 ng/mL and showed good back-calculated accuracy and precision. Intra- and inter-day precision and accuracy, determined on three quality control levels were always <12.8 % and between 90.1 and 106.9 %, respectively. The cross-validation procedure showed a good reproducibility between the two methods, the percentage differences within 20 % in more than 70 % of the total amount of clinical samples analysed.
authors.affiliation: Lab. NIB, Pediatric Research Institute, Città della Speranza, Corso Stati Uniti 4, 35127, Padua, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Calandra
authors.affiliation: Experimental and Clinical Pharmacology Division, Department of Translational Research, IRCCS-National Cancer Institute, Via Franco Gallini 2, 33081, Aviano, Italy.
authors.forename: Bianca
authors.initials: B
authors.lastname: Posocco
authors.affiliation: Lab. NIB, Pediatric Research Institute, Città della Speranza, Corso Stati Uniti 4, 35127, Padua, Italy. s.crotti@irpcds.org.
authors.forename: Sara
authors.initials: S
authors.lastname: Crotti
authors.affiliation: Experimental and Clinical Pharmacology Division, Department of Translational Research, IRCCS-National Cancer Institute, Via Franco Gallini 2, 33081, Aviano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Marangon
authors.affiliation: Experimental and Clinical Pharmacology Division, Department of Translational Research, IRCCS-National Cancer Institute, Via Franco Gallini 2, 33081, Aviano, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Giodini
authors.affiliation: Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Via Nicolo Giustiniani 2, 35128, Padua, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.affiliation: Experimental and Clinical Pharmacology Division, Department of Translational Research, IRCCS-National Cancer Institute, Via Franco Gallini 2, 33081, Aviano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
authors.affiliation: Lab. NIB, Pediatric Research Institute, Città della Speranza, Corso Stati Uniti 4, 35127, Padua, Italy.|IENI CNR, Corso Stati Uniti 4, 35127, Padua, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Traldi
authors.affiliation: Lab. NIB, Pediatric Research Institute, Città della Speranza, Corso Stati Uniti 4, 35127, Padua, Italy.|Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Via Nicolo Giustiniani 2, 35128, Padua, Italy.|Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Agostini
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D000077146:Irinotecan; D008657:Metabolic Clearance Rate; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D002166:Camptothecin
keywords: Bioanalytical methods; Drug monitoring/drug screening; Irinotecan; MALDI-TOF