title: Recent developments in the chromatographic bioanalysis of approved kinase inhibitor drugs in oncology.
abstract: In recent years (2010-present) there has been an increase in the number of publications reporting the development, validation and use of bioanalytical methods in the rapidly expanding drug class of small molecule protein kinase inhibitors. Most reports describe the technological set-up of the methods that have allowed for drug concentration measurements from various sample types. This includes plasma, dried blood-spot, and tissue-analysis. Also method development, exploration of various techniques, as well as measurement and identification of metabolites were addressed. For the bioanalysis, a variety of sample-pretreatment methods like protein-precipitation, liquid-liquid extraction, and solid-phase extraction have been employed, all varying in complexity, cleanliness and time-consumption. Chromatographic separation, nowadays, is more focused on separating components from ion-suppressive effects, since for MS/MS detection, various components do not have to be baseline separated. For detection multiple types of detectors were used, ranging from state-of-the-art high resolution, and tandem mass spectrometry with low picogram per milliliter detection limits to the classical UV-detector with several nanograms per milliliter limits. As new bioanalytical methods have arisen that do rely on chromatographic separation, for example for high-throughput analysis, these are addressed in this review as well.
authors.affiliation: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. Electronic address: j.j.m.rood@uu.nl.
authors.forename: Johannes J M
authors.initials: JJM
authors.lastname: Rood
authors.affiliation: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands; The Netherlands Cancer Institute, Department of Clinical Pharmacology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Jan H M
authors.initials: JHM
authors.lastname: Schellens
authors.affiliation: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands; The Netherlands Cancer Institute, Department of Clinical Pharmacology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; MC Slotervaart, Department of Pharmacy & Pharmacology, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.affiliation: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Sparidans
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis* / Q000378:metabolism* / Q000627:therapeutic use; D001826:Body Fluids / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods / Q000639:trends; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000378:metabolism* / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000639:trends
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: Chromatographic bioanalysis; Kinase inhibitor; LC–MS/MS; Oncology