title: Preanalytical Stability of Gemcitabine and its Metabolite 2', 2'-Difluoro-2'-Deoxyuridine in Whole Blood-Assessed by Liquid Chromatography Tandem Mass Spectrometry.
abstract: Gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) and metabolite (2',2'-difluoro-2'-deoxyuridine, dFdU) quantification is warranted for individualized treatment strategies. Analyte stability is crucial for the validity of such quantification. We therefore studied the impact of the time interval from blood sampling to separation of plasma on gemcitabine stability. Blood from gemcitabine-treated patients was drawn into tetrahydrouridine (THU)-spiked heparin and ethylenediaminetetraacetic acid tubes and kept on ice until separation. Plasma was separated sequentially up to 24 h after sampling and dFdC and dFdU were quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS). The change in plasma concentrations over time was compared with the highest imprecision for concentrations above the lower limit of quantification of the LC-MS/MS method. Analyte concentrations decreased slightly over time, but for samples stored for 4 h on ice, the decline was smaller than the expected analytical imprecision. After 24 h, the maximum decline was 14.0%, which exceeded the expected analytical imprecision. dFdC and dFdU stabilities were acceptable for at least 4 h when THU-spiked whole blood samples were kept on ice. This is within the scope of routine sampling procedures. Further, variations in separation time intervals within this time frame are negligible when interpreting drug concentrations.
authors.affiliation: Laboratory of Clinical Biochemistry, Section of Clinical Pharmacology, Haukeland University Hospital, Bergen 5020, Norway. Electronic address: tormod.karlsen.bjanes@helse-bergen.no.
authors.forename: Tormod
authors.initials: T
authors.lastname: Bjånes
authors.affiliation: Laboratory of Clinical Biochemistry, Section of Clinical Pharmacology, Haukeland University Hospital, Bergen 5020, Norway.
authors.forename: Tina
authors.initials: T
authors.lastname: Kamčeva
authors.affiliation: Faculty of Medicine and Dentistry, Institute of Clinical Science, University of Bergen, Bergen 5021, Norway.
authors.forename: Torunn
authors.initials: T
authors.lastname: Eide
authors.affiliation: Laboratory of Clinical Biochemistry, Section of Clinical Pharmacology, Haukeland University Hospital, Bergen 5020, Norway; Faculty of Medicine and Dentistry, Institute of Clinical Science, University of Bergen, Bergen 5021, Norway.
authors.forename: Bettina
authors.initials: B
authors.lastname: Riedel
authors.affiliation: Laboratory of Clinical Biochemistry, Section of Clinical Pharmacology, Haukeland University Hospital, Bergen 5020, Norway; Faculty of Medicine and Dentistry, Institute of Clinical Science, University of Bergen, Bergen 5021, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Schjøtt
authors.affiliation: Faculty of Medicine and Dentistry, Institute of Clinical Science, University of Bergen, Bergen 5021, Norway.
authors.forename: Asbjørn
authors.initials: A
authors.lastname: Svardal
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D006801:Humans; D053719:Tandem Mass Spectrometry / Q000379:methods; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003841:Deoxycytidine; C084565:2',2'-difluoro-2'-deoxyuridine; D000093542:Gemcitabine
keywords: HPLC; analysis; cancer chemotherapy; clinical pharmacokinetics; stability