title: Liquid chromatography-tandem mass spectrometry assay for the quantification of niraparib and its metabolite M1 in human plasma and urine.
abstract: Niraparib (MK-4827) is a novel poly(ADP-Ribose) polymerase (PARP) inhibitor currently investigated in phase III clinical trials to treat cancers. The development of a new drug includes the characterisation of absorption, metabolism and excretion (AME) of the compound. AME studies are a requirement of regulatory agencies and for this purpose bioanalytical assays are essential. This article describes the development and validation of a bioanalytical assay for niraparib and its carboxylic acid metabolite M1 in human plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample pre-treatment involved protein precipitation for plasma and dilution of urine samples using acetonitrile-methanol (50:50, v/v). Final extracts were injected onto a SunFire C18 column and gradient elution using 20mM ammonium acetate (mobile phase A) and formic acid:acetonitrile:methanol (0.1:50:50, v/v/v) (mobile phase B) was applied. Detection was performed on an API5500 tandem mass spectrometer operating in the positive electrospray ionisation mode applying multiple reaction monitoring (MRM). The assay was successfully validated in accordance with the Food and Drug Administration and latest European Medicines Agency guidelines on bioanalytical method validation and can therefore be applied in pharmacological clinical studies.
authors.affiliation: Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands. Electronic address: l.v.andel@nki.nl.
authors.forename: L
authors.initials: L
authors.lastname: van Andel
authors.affiliation: Tesaro Inc., Waltham, MA, United States.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Tesaro Inc., Waltham, MA, United States.
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.affiliation: Tesaro Inc., Waltham, MA, United States.
authors.forename: V
authors.initials: V
authors.lastname: Kansra
authors.affiliation: Tesaro Inc., Waltham, MA, United States.
authors.forename: S
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Tesaro Inc., Waltham, MA, United States.
authors.forename: L
authors.initials: L
authors.lastname: Hughes
authors.affiliation: Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Tibben
authors.affiliation: Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Gebretensae
authors.affiliation: Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Rosing
authors.affiliation: Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: J H M
authors.initials: JHM
authors.lastname: Schellens
authors.affiliation: Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D007191:Indazoles / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D057230:Limit of Detection; D010880:Piperidines / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007191:Indazoles; D010880:Piperidines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C545685:niraparib
keywords: Bioanalysis; HPLC–MS/MS; MK-4827; Niraparib; Pharmacokinetics