: Ribavirin monitoring

International audienceRibavirin, a nucleoside analog, is administered in combination with interferon to patients with chronic hepatitis C. To evaluate the feasibility of ribavirin therapeutic drug monitoring, we investigated the influence of blood collection and preanalytical conditions on ribavirin concentrations and compared the results obtained from interlaboratory blind tests by 3 laboratories using different analytical techniques. On 3 occasions, blank serum samples spiked with ribavirin and pooled serum samples from patients on ribavirin were sent to the 3 laboratories. Two analytical techniques were based on liquid chromatography with tandem mass spectrometry (LC-MS/MS) and 1 on high-performance liquid chromatography with UV detection (HPLC-UV), with protein precipitation or solid-phase extraction, all validated according to international guidelines. Inter- and intra-batch mean relative errors ranged from -7.4% to +10.3% and from -10.3% to +7.4%, respectively. Relative standard deviations were 0.991) for all 3 methods. The 2 LC-MS/MS techniques were slightly less precise and accurate than HPLC-UV, perhaps because the internal standard used was not a ribavirin isotope. Accurate and precise LC-MS/MS and HPLC-UV methods developed in 3 different laboratories provided excellent and consistent results to blind tests for ribavirin determination in spiked serum samples and pools of serum samples from patients with chronic hepatitis C virus infection

Lethal cerebral hemorrhage after ticagrelor intoxication: a specific antidote is urgently needed

International audienc

Infliximab quantitation in human plasma by liquid chromatography-tandem mass spectrometry: towards a standardization of the methods?

International audienceInfliximab (IFX) is a chimeric monoclonal antibody targeting tumor necrosis factor-alpha. It is currently approved for the treatment of certain rheumatic diseases or inflammatory bowel diseases. Clinical studies have suggested that monitoring IFX concentrations could improve treatment response. However, in most studies, IFX was quantified using ELISA assays, the resulting discrepancies of which raised concerns about their reliability. Here, we describe the development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for IFX quantification in human plasma. Full-length stable-isotope-labeled antibody (SIL-IFX) was added to plasma samples as internal standard. Samples were then prepared using Mass Spectrometry Immuno Assay (MSIA™) followed by trypsin digestion and submitted to multiple reaction monitoring (MRM) for quantification of IFX. The chromatographic run lasted 13 min. The range of quantification was 1 to 26 mg/L. For two internal quality controls spiked with 6 and 12 mg/L of IFX, the method was reproducible (coefficients of variation (CV%): 12.7 and 2.1), repeatable (intra-day CV%: 5.5 and 5.0), and accurate (inter-day and intra-day deviations from nominal values: +6.4 to +3.7 % and 5.5 to 9.2 %, respectively). There was no cross - contamination effect. Samples from 45 patients treated with IFX were retrospectively analyzed by LC-MS/MS and results were compared to those obtained with an in-house ELISA assay and the commercial Lisa Tracker® method. Good agreement was found between LC-MS/MS and in-house ELISA (mean underestimation of 13 % for in-house ELISA), but a significant bias was found with commercial ELISA (mean underestimation of 136 % for commercial ELISA). This method will make it possible to standardize IFX quantification between laboratories. Graphical Abstract Interassay comparison of the three methods: LC-MS/MS vs inhouse ELISA assay or vs Lisa Tracker® ELISA assays, Passing & Bablok (a) and Bland & Altman (b) for the comparison of LC-MS/MS vs in-house ELISA assay; Passing & Bablo