Immunsuppressiva-Medikamentenspiegelmessung – reine Routine? / Immunosuppressant drug monitoring – a routine undertaking?

The quantitative assessment of immunosuppressant drug levels is still one of the most challenging therapeutic drug monitoring procedures in clinical routine. During the past years, several technical developments matured to useable methods. In addition to immunoassays, liquid chromatography- tandem mass spectrometry has become a key method in immunosuppressant therapeutic drug monitoring. This overview should aid in understanding the advantages and disadvantages of the various assays and methods. UKNEQAS proficiency testing results are used for an inter-assay comparison approach

Immunsuppressiva-Medikamentenspiegelmessung – reine Routine? / Immunosuppressant drug monitoring – a routine undertaking?

The quantitative assessment of immunosuppressant drug levels is still one of the most challenging therapeutic drug monitoring procedures in clinical routine. During the past years, several technical developments matured to useable methods. In addition to immunoassays, liquid chromatography- tandem mass spectrometry has become a key method in immunosuppressant therapeutic drug monitoring. This overview should aid in understanding the advantages and disadvantages of the various assays and methods. UKNEQAS proficiency testing results are used for an inter-assay comparison approach

Some important aspects of implementing tandem mass spectrometry in a routine clinical laboratory environment

Tijekom posljednjih godina kombinacija tekućinske kromatografije visoke učinkovitosti (engl. high performance liquid chromatography, HPLC) i dvojne spektrometrije masa (engl. tandem mass spectrometry, MS/MS) (kombinacija koja je također poznata kao HPLC-MS/MS), postala je pouzdani analitički postupak. Njena primjena u terapijskom praćenju koncentracije lijeka (engl. therapeutic drug monitoring, TDM) pokazala se boljom od uobičajeno primjenjivanih imunokemijskih analiza. Ta je tehnika postala obveznim pomagalom u mnogim kliničkim laboratorijima, posebice u kontekstu praćenja koncentracije imunosupresijskih lijekova gdje se smatra "zlatnim" standardom. Međutim, postavljanje uređaja za HPLC-MS/MS je zahtjevno u smislu validacije analiza te robusnosti mjerenja. U ovom se pregledu daje gruba smjernica kao pomoć u procesu uspostave takvih uređaja u rutinskim kliničkim uvjetima.During past years, the combination of high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS), also known as HPLC-MS/MS, matured to reliable analytical instrumentation. Its application in therapeutic drug monitoring (TDM) has been shown to be superior to normally applied immunoassays. Especially in the context of immunosuppressant medication level surveillance, this technique has become an indispensable tool in many clinical laboratories and is considered the gold standard. However, setting up a HPLC-MS/MS platform is demanding in terms of assay validation and the robustness of testing. This review is to provide a rough guideline aiding the implementation process of such a platform into a routine clinical environment

Evaluation of five multisteroid LC‒MS/MS methods used for routine clinical analysis: comparable performance was obtained for nine analytes

Objectives: A mass spectrometry (LC‒MS/MS)-based interlaboratory comparison study was performed for nine steroid analytes with five participating laboratories. The sample set contained 40 pooled samples of human serum generated from preanalyzed leftovers. To obtain a well-balanced distribution across reference intervals of each steroid, the leftovers first underwent a targeted mixing step. Methods: All participants measured a sample set once using their own multianalyte protocols and calibrators. Four participants used in-house developed measurement platforms, including IVD-CE certified calibrators, which were used by three participants; the 5th lab used the whole LC‒MS kit from an IVD manufacturer. All labs reported results for 17-hydroxyprogesterone, androstenedione, cortisol, and testosterone, and four labs reported results for 11-deoxycortisol, corticosterone, cortisone, dehydroepiandrosterone sulfate (DHEAS), and progesterone. Results: Good or acceptable overall comparability was found in Bland‒Altmann and Passing‒Bablok analyses. Mean bias against the overall mean remained less than ±10 % except for DHEAS, androstenedione, and progesterone at one site and for cortisol and corticosterone at two sites (max. -18.9 % for androstenedione). The main analytical problems unraveled by this study included a bias not previously identified in proficiency testing, operator errors, non-supported matrix types and higher inaccuracy and imprecision at lower ends of measuring intervals. Conclusions: This study shows that intermethod comparison is essential for monitoring the validity of an assay and should serve as an example of how external quality assessment could work in addition to organized proficiency testing schemes

Hyperthyroxinemia and Hypercortisolemia due to Familial Dysalbuminemia.

A 23-year-old man and his grandmother with hyperthyroxinemia and hypercortisolemia were heterozygous for an ALB mutation (p. Arg218Pro), known to cause familial dysalbuminemic hyperthyroxinemia (FDH). However, serum-free cortisol levels in these individuals were normal and total cortisol concentrations fell markedly after depletion of albumin from their serum. We conclude that binding of steroid as well as iodothyronines to mutant albumin causes raised circulating cortisol as well as thyroid hormones in euthyroid euadrenal individuals with R218P FDH, with potential for misdiagnosis, unnecessary investigation, and inappropriate treatment.Wellcome Trust NIHR Cambridge Biomedical Research Centr

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe