Measurement uncertainty estimation of free drug concentrations in clinical laboratories using equilibrium dialysis.

Objectives: Developing procedures based on equilibrium dialysis (ED) that allow measuring the free drug concentration in plasma improves therapeutic drug monitoring (TDM) in those cases where its measurement is justified. However, this procedure requires specific sample preparation and presents different pitfalls, which are not error-free. As with any result provided by a clinical laboratory, this one should be as accurate as possible to allow a correct clinical interpretation.

State of affairs and future challenges in laboratory medicine in Spain: an analysis of the Spanish Society of Laboratory Medicine (SEQC).

Objectives: Laboratory Medicine is a crucial discipline that contributes to the diagnosis, management and monitoring of patients. This branch of medicine faces two major challenges: New technologies and increased demand. There is limited information available of the state of affairs in Laboratory Medicine in Spain.

Validation of new automated turbidimetric immunoassays for the measurement of haptoglobin and inter-α-trypsin inhibitor heavy chain H4 specific for the bovine species.

Background: Good strategical programs are required for the early detection of disease even in the absence of evident clinical signs, which is crucial in satisfying animal welfare. Haptoglobin (Hp) and inter-α-trypsin inhibitor heavy chain H4 (ITIH4) are acute phase proteins and good biomarkers of early inflammation in cattle, with plasma levels that significantly increase after injury or infection.

Objectives: We aimed to develop and validate two new immunoturbidimetric methods for Hp and ITIH4.

Estimation of the uncertainty of values assigned to calibration materials prepared in-house: An example for hydroxychloroquine calibrators in blood-hemolysate-based matrix.

Background: Hydroxychloroquine is an antimalarial drug that has been prescribed for the treatment of patients with COVID-19 infection. To assist in clinician decision-making, several clinical laboratories have developed and validated measurement procedures in-house based on HPLC or HPLC-MS/MS to measure the mass concentration of hydroxychloroquine in different biological fluids. In these cases, laboratories produce their calibration materials but rarely estimate the measurement uncertainty of their assigned values.

Estimation of the measurement uncertainty and practical suggestion for the description of the metrological traceability in clinical laboratories.

Clinicians request a large part of measurements of biological quantities that clinical laboratories perform for diagnostic, prognostic or diseases monitoring purposes. Thus, laboratories need to provide patient's results as reliable as possible. Metrological concepts like measurement uncertainty and metrological traceability allow to know the accuracy of these results and guarantee their comparability over time and space.

Big data and reference intervals: rationale, current practices, harmonization and standardization prerequisites and future perspectives of indirect determination of reference intervals using routine data.

Reference intervals are commonly used as a decision-making tool. In this review, we provide an overview on "big data" and reference intervals, describing the rationale, current practices including statistical methods, essential prerequisites concerning data quality, including harmonization and standardization, and future perspectives of the indirect determination of reference intervals using routine laboratory data.

Reference change values based on uncertainty models.

Background: Different reference change values approaches are widely accepted to interpret the change between two consecutive measured values from the same biological quantity in an individual. Nevertheless, we propose two uncertainty-based models to estimate reference change values which will include all possible variation sources.

Methods: The models consisted in 1) estimation of the uncertainty related to each measured value, 2) calculation of the change between these values and its uncertainty, and 3) performing a compatibility study to know if the values are of the same degree of equivalence.

Measurement uncertainty of β-lactam antibiotics results: estimation and clinical impact on therapeutic drug monitoring.

Background Despite that measurement uncertainty data should facilitate an appropriate interpretation of measured values, there are actually few reported by clinical laboratories. We aimed to estimate the measurement uncertainty of some β-lactam antibiotics (β-LA), and to evaluate the impact of reporting the measurement uncertainty on clinicians' decisions while guiding antibiotic therapy. Methods Measurement uncertainty of β-LA (aztreonam [ATM], cefepime [FEP], ceftazidime [CAZ], and piperacillin [PIP]) values, obtained by an UHPLC-MS/MS based-method, was estimated using the top-down approach called the single laboratory validation approach (EUROLAB guidelines).

Age-Related Serum Biochemical Reference Intervals Established for Unweaned Calves and Piglets in the Post-weaning Period.

The purpose of the present study is to establish the influence of age on serum biochemistry reference intervals (RIs) for unweaned calves and recently-weaned piglets using large number of animals sampled at different ages from populations under different season trials. Specifically, milk replacer (MR)-fed calves from April-July 2017 ( = 60); from December 2016-March 2017 ( = 76) and from April-August 2018 ( = 57) and one group of healthy weaned piglets ( = 72) were subjected to the study. Serum enzymes and metabolites of calves at age of 24 h (24 h after colostrum intake), 2, 5, and 7 weeks from merged trials and piglets at 0, 7, and 14 days post-weaning (at 21, 28, and 35 days of age) were studied.

Traceability of immunosuppressant's mass concentration results obtained using different commercial calibrators.

Background: Due to the high inter-variability in immunosuppressants pharmacokinetics, therapeutic drug monitoring of these drugs is essential in order to minimize the risk of rejection after organ transplantation. Thus, results facilitated to clinicians by clinical laboratories for these drugs should be as reliable as possible. The knowledge of metrological traceability and performing compatibility studies can allow ensuring reliability of these results, mainly, when laboratories introduce substantial changes in their measurement procedures, e.

Different top-down approaches to estimate measurement uncertainty of whole blood tacrolimus mass concentration values.

Background: Values of mass concentration of tacrolimus in whole blood are commonly used by the clinicians for monitoring the status of a transplant patient and for checking whether the administered dose of tacrolimus is effective. So, clinical laboratories must provide results as accurately as possible. Measurement uncertainty can allow ensuring reliability of these results.

Measurement uncertainty and metrological traceability of whole blood cyclosporin A mass concentration results obtained by UHPLC-MS/MS.

Background: Traceable and accurate results of cyclosporine A (CsA) mass concentrations in whole blood are required to ensure the monitoring of immunosuppressive therapy in transplant recipients. Metrological traceability and measurement uncertainty can allow ensuring reliability and comparability of these results over time and space. In this study, we provide a practical and detailed example of how the traceability and uncertainty of mass concentration of CsA results, obtained using an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) procedure, can be described and estimated.

Preparation of canine C-reactive protein serum reference material: A feasibility study.

Background: The availability of a species-specific reference material is essential for the harmonization of results obtained in different laboratories by different methods.

Objectives: We describe the preparation of a canine C-reactive protein (cCRP) serum reference material containing purified cCRP stabilized in a serum matrix. The material can be used by manufacturers to assign values to their calibrator and control materials.

A new automated turbidimetric immunoassay for the measurement of canine C-reactive protein.

Background: In dogs, as in humans, C-reactive protein (CRP) is a major acute phase protein that is rapidly and prominently increased after exposure to inflammatory stimuli. CRP measurements are used in the diagnosis and monitoring of infectious and inflammatory diseases.

Objectives: The study aim was to develop and validate a turbidimetric immunoassay for the quantification of canine CRP (cCRP), using canine-specific reagents and standards.

An approach to establish the uncertainty budget of catalytic activity concentration measurements in a reference laboratory.

Background: Reference laboratories providing reference services recognized by the Joint Committee for Traceability in Laboratory Medicine (JCTLM) must be accredited as calibration laboratories according to ISO 17025 and ISO 15195. These standards require laboratories to establish an uncertainty budget, in which the uncertainty contributions of the relevant uncertainty components are specified. We present a model to estimate the measurement uncertainty of creatine kinase catalytic activity concentration results obtained by IFCC primary reference measurement procedure.

Evaluation of commutability of several materials for harmonization alkaline phosphatase catalytic concentration measurements.

Background: The International Standard ISO 18153 establish that one of the requirements to assure the metrological traceability of values for catalytic concentration of enzymes is the commutability of calibrator and control materials used in the reference measurement systems. This approach was applied to verify the commutability of several commercial stabilized materials using the recently published alkaline phosphatase IFCC primary reference procedure and two routine procedures.

Methods: ALP catalytic activity was measured in 50 serum samples and 16 commercial materials, including control materials from EQAS programs, using primary reference measurement procedure and two routine measurement procedures with AMP and DEA as buffers.

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 °C. Part 9: reference procedure for the measurement of catalytic concentration of alkaline phosphatase International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Scientific Division, Committee on Reference Systems of Enzymes (C-RSE) (1)).

Abstract This paper is the ninth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 °C and the certification of reference preparations. Other parts deal with: Part 1. The concept of reference procedures for the measurement of catalytic activity concentrations of enzymes; Part 2.

Traceability of values for catalytic activity concentration of enzymes: a Certified Reference Material for aspartate transaminase.

Background: A new reference material for the liver enzyme aspartate transaminase (AST) (L-aspartate: 2-oxoglutarate-aminotransferase, EC 2.6.1.

IFCC reference procedures for measurement of the catalytic concentrations of enzymes: corrigendum, notes and useful advice. International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)--IFCC Scientific Division.

The primary reference measurement procedures (PRMPs) for the international standardization of catalytic concentration measurements of alpha-amylase, alanine aminotransferase, aspartate aminotransferase (AST), creatine kinase (CK), gamma-glutamyltransferase and lactate dehydrogenase have been performed in reference laboratories for several years. The IFCC Committee on Reference Systems for Enzymes and two reference laboratories, with official accreditation for the PRMPs, have collected useful information on some of the steps of the reference procedures that require special attention. This document comprises errata corrige for minor mistakes in published PRMPs for AST and CK.

Validation of an immunoturbidimetric method for determination of porcine serum C-reactive protein.

Measurement of porcine C-reactive protein (CRP) in serum is an important tool for monitoring health and welfare in pigs. In this study, an immunoturbidimetric method from Olympus System Reagent (OSR 6147) used to measure human CRP in serum that employ a human traceable calibrator has been evaluated in porcine serum samples. Intra- and inter-assay imprecision were lower than that obtained with the porcine-specific commercially available ELISA.

Metrological traceability of values for alpha-amylase catalytic concentration assigned to a commutable calibrator materials.

Background: The International Standard ISO 18153 describes how to assure the metrological traceability of catalytic concentration values assigned to commercial calibration materials following the reference measurement system. We applied this approach to the standardization of alpha-amylase measurements.

Methods: Traceable values of catalytic activity with measurement uncertainty were assigned to three commercial calibrator materials using alpha-amylase primary reference measurement procedure described by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

Purification of recombinant histidine-tag streptolysin O using immobilized metal affinity expanded bed adsorption (IMA-EBA).

In this report, we describe the recombinant SLO expression as a fusion protein with a C-terminal hexahistidine tag and its purification using immobilized metal affinity expanded bed adsorption (STREAMLINE(trade mark) Chelating). In order to facilitate downstream processing of the purification, an efficient fermentation process was developed focusing on the achievement of high yields of soluble protein. The purification strategy resulted in a 40% recovery of active recombinant SLO and the protein was purified eight-fold.

Metrological traceability of values for catalytic concentration of enzymes assigned to a calibration material.

Background: The metrological traceability of values for the catalytic concentration of several enzymes assigned to a calibration material has been assured by following the recently published International Standard ISO 18153.

Methods: A traceable value with a measurement uncertainty was assigned for the catalytic concentration of alanine aminotransferase, creatine kinase, gamma-glutamyltransferase and lactate dehydrogenase in two materials from different sources. These are all measurable quantities, with the primary reference measurement procedure described by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and a primary calibrator giving metrological traceability to the SI unit of measurement.