title: Determination of irinotecan and SN38 in human plasma by TurboFlow™ liquid chromatography-tandem mass spectrometry.
abstract: Irinotecan is a cytotoxic agent used in the treatment of metastatic colorectal cancer. Irinotecan is a prodrug when is converted in vivo to an active metabolite SN38, which has potent pharmacological activity. SN38 is then inactivated and excreted as SN38-glucuronide. High-performance liquid chromatography-mass spectrometry is a widely used bioanalysis technique that can be coupled to the turbulent-flow extraction line to shorten preparation time. A technique was developed to quantify irinotecan and its metabolite by liquid chromatography-tandem mass spectrometry coupled with a turbulent-flow online extraction method. Assays were performed on 100 μL of plasma after protein precipitation. The supernatant is injected directly into the extraction column, transferred to the chromatographic column, and analyzed by tandem mass spectrometry. Linearity, reproducibility and repeatability of the method were validated on a concentration range of 25-2500 ng/mL for irinotecan and 5-500 ng/mL for SN38. For the low limit of quantification of irinotecan and SN38, precision is 6.31% and 8.73%, and accuracy is 84.0% and 91.8%, respectively. The SN38-glucuronide determination protocol included a hydrolyzation step. This method was successfully used to quantify irinotecan, SN38 and SN38-G in human plasma in a clinical trial.
authors.affiliation: CHU Clermont-Ferrand, Service de Pharmacologie Médicale, BP69, F-63003 Clermont-Ferrand, France; INSERM, U 1107, Neuro-Dol, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France. Electronic address: pherviou@chu-clermontferrand.fr.
authors.forename: P
authors.initials: P
authors.lastname: Herviou
authors.affiliation: CHU Clermont-Ferrand, Service de Pharmacologie Médicale, BP69, F-63003 Clermont-Ferrand, France; INSERM, U 1107, Neuro-Dol, F-63000 Clermont-Ferrand, France.
authors.forename: D
authors.initials: D
authors.lastname: Richard
authors.affiliation: CHU Clermont-Ferrand, Service de Pharmacologie Médicale, BP69, F-63003 Clermont-Ferrand, France; INSERM, U 1107, Neuro-Dol, F-63000 Clermont-Ferrand, France.
authors.forename: L
authors.initials: L
authors.lastname: Roche
authors.affiliation: CHU Clermont-Ferrand, Service de Pharmacologie Médicale, BP69, F-63003 Clermont-Ferrand, France; INSERM, U 1107, Neuro-Dol, F-63000 Clermont-Ferrand, France.
authors.forename: J
authors.initials: J
authors.lastname: Pinguet
authors.affiliation: CHU Clermont-Ferrand, Service de Pharmacologie Médicale, BP69, F-63003 Clermont-Ferrand, France; INSERM, U 1107, Neuro-Dol, F-63000 Clermont-Ferrand, France; Clermont Université, Faculté de Médecine, Laboratoire de Pharmacologie Médicale, BP 10448, F-63000 Clermont-Ferrand, France.
authors.forename: F
authors.initials: F
authors.lastname: Libert
authors.affiliation: CHU Clermont-Ferrand, Service de Pharmacologie Médicale, BP69, F-63003 Clermont-Ferrand, France; INSERM, U 1107, Neuro-Dol, F-63000 Clermont-Ferrand, France; Clermont Université, Faculté de Médecine, Laboratoire de Pharmacologie Médicale, BP 10448, F-63000 Clermont-Ferrand, France.
authors.forename: A
authors.initials: A
authors.lastname: Eschalier
authors.affiliation: Centre Jean Perrin, F-63011 Clermont-Ferrand, France; CREAT EA 7283, Université d'Auvergne, F-63000 Clermont-Ferrand, France; Centre d'Investigation Clinique, Inserm U501, F-63000 Clermont-Ferrand, France.
authors.forename: X
authors.initials: X
authors.lastname: Durando
authors.affiliation: CHU Clermont-Ferrand, Service de Pharmacologie Médicale, BP69, F-63003 Clermont-Ferrand, France; INSERM, U 1107, Neuro-Dol, F-63000 Clermont-Ferrand, France; Clermont Université, Faculté de Médecine, Laboratoire de Pharmacologie Médicale, BP 10448, F-63000 Clermont-Ferrand, France.
authors.forename: N
authors.initials: N
authors.lastname: Authier
mesh_terms: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D000077146:Irinotecan; D011355:Prodrugs / Q000032:analysis*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D011355:Prodrugs; D000077146:Irinotecan; D002166:Camptothecin
keywords: High-turbulence liquid chromatography; Human plasma; Irinotecan; LC–MS/MS