title: Stability of ribavirin concentrations depending on the type of blood collection tube and preanalytical conditions.
abstract: Ribavirin pharmacokinetic and exposure effect trials based on either plasma or serum concentrations have yielded diverging results. This study aimed to compare ribavirin concentrations in serum and plasma and to investigate the influence of blood collection and preanalytical conditions on ribavirin concentration stability. Blood samples from patients with hepatitis virus C and receiving ribavirin were collected in plain (dry) tubes, in tubes containing ethylenediaminetetra-acetic acid or lithium-heparinate, in Type II Serum Separating Tubes with clot activator, or Type II lithium heparinate Plasma Separating Tubes. Different time and temperature conditions were tested before and after blood centrifugation. Ribavirin was determined using liquid chromatography-dual mass spectroscopy. Multiple-way analysis of variance was used for statistical analyses. Ribavirin concentrations showed a higher interlaboratory variability in serum than in plasma. Results were fairly stable over 2 hours in whole blood collected in dry or ethylenediaminetetra-acetic acid tubes and very stable up to 24 hours in serum or plasma kept in gel-containing tubes after immediate centrifugation. When Plasma Separating II gel tubes were kept at +4 degrees C or at ambient temperature for up to 24 hours before centrifugation, ribavirin concentrations decreased by 1% to 8% and 12% to 18%, respectively. These results suggest that blood samples should be collected in gel-containing tubes and centrifuged immediately, after which the tubes can be kept at ambient temperature for the next 24 hours. In case of clinical constraints, Plasma Separating II gel tubes can be kept at +4 degrees C for a maximum of 2 hours before centrifugation with limited impact on the measured concentrations.
authors.affiliation: Department of Pharmacology-Toxicology, CHU Limoges, Limoges, France. pierre.marquet@unilim.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.forename: François-Ludovic
authors.initials: FL
authors.lastname: Sauvage
authors.forename: Véronique
authors.initials: V
authors.lastname: Loustaud-Ratti
authors.forename: Gérard
authors.initials: G
authors.lastname: Babany
authors.forename: Annick
authors.initials: A
authors.lastname: Rousseau
authors.forename: Gérard
authors.initials: G
authors.lastname: Lachâtre
mesh_terms: D001800:Blood Specimen Collection / Q000379:methods* / Q000592:standards*; D002623:Chemistry Techniques, Analytical / Q000379:methods / Q000592:standards; D004355:Drug Stability; D006801:Humans; D012254:Ribavirin / Q000032:analysis / Q000097:blood*; D013048:Specimen Handling / Q000379:methods / Q000592:standards
chemical_list: D012254:Ribavirin