Research project NM/A/15 (Research action NM)
CONTEXT
It is essential to have harmonised and reliable analytical methods in routine analysis. The goal of many analytical methods is to gain information so that important decisions can be taken, for instance, about compliance with governmental regulations. Uncertainty is a basic performance characteristic of measurement results that is fundamental if comparability among results is to be assured and if users are to be able to rely on them. Thus, this project will mainly focus on the development of norms and guidelines for the estimation of measurement uncertainty in chemical and pharmaceutical laboratories.
THE PROJECT
-Goals
The aim of the project is to develop norms and guidelines for the practical estimation of uncertainty in analytical measurements obtained from methods applied in the chemical, agro-food and related industries. It will mainly concern high performance liquid chromatography and capillary electrophoresis methods for the analysis of bulk pharmaceutical compounds, for the bioanalysis of drugs in the frame of pharmacokinetic studies and for the chiral analysis of drugs.
METHODOLOGY
In order to achieve the objectives of the project, the network intends to use the following strategy:
- first, the existing situation and in particular the two approaches used to determine the uncertainty on a measurement will be examined, namely the ISO approach, commonly known as "bottom-up", and the Analytical Method Committee approach, commonly known as "top-down";
- second, some fields of application will be investigated and a few technical problems such as sampling, matrix effects, quality control, limits of detection and quantisation, will be studied in order to define general guidelines;
- third, the general guidelines including a « menu-driven » approach and finalised standard procedures will be developed. These procedures should be practical and cost-efficient;
- finally, the network will try to obtain acceptance of the proposed guidelines.
THE PARTNERS
The project is led by a working group consisting of the "Department of Analytical Pharmaceutical Chemistry, Ulg", the "Department of Pharmaceutical and Biomedical Analysis, VUB" and the "Laboratorium voor Farmaceutische Chemie en Analyse van Geneesmiddelen, KUL".
Role/activities of each partners as part of the project:
- The collection of the material and the existing situations as well as the study of particular themes are evaluated by ULg, KUL and VUB.
- For the estimation of uncertainty of an individual analytical result obtained from validated procedures, novel methods for the analysis of drugs are developed by KUL; ULg participates to a SFSTP commission "Validation in biological media" and contributes to the elaboration of the present recommendations. A new SFSTP commission entitled "Uncertainty in analytical measurements" is initiated by ULg. In addition, ULg participates to interlaboratory tests and develops some novel analytical methods, which will contribute to the study of the relationship between validation and uncertainty estimation. VUB is concerned by the identification and combination of sources of error as well as the treatment of systematic errors. VUB also participates to interlaboratory tests.
- Concerning specific and technical problems related to uncertainty, the three universities envisage the study of problems by considering sampling, matrix effects, quality control and limits of detection and quantisation.
- Finally, the last activity concerns the definition and assessment of a set of minimal guidelines for the determination of uncertainty in analysis laboratory and its assessment in the analytical reports.
EXPECTED PRODUCTS AND RESULTS
Since the difficulty of applying the ISO approach in chemical measurements hampers its widespread use, the approach presented by the Analytical Methods Committee was used. It is based on the information gathered from interlaboratory exercises. At the present stage, four analytical protocols were elaborated. Two exercises have been completed and statistical treatments were performed.
At the end of this project, the expected results will be to define a general approach including a "menu-driven" one and to establish standard procedures. These procedures should be practical and cost-efficient. Therefore, a set of minimal guidelines will be defined and one will try to obtain their acceptance in order to valorise the expected results.
SCIENTIFIC COLLABORATIONS
International collaborations with pharmaceutical and chemical industries as well as university laboratories.
USERS COMMITTEE
A users committee is included in this project. Some members of this committee are representative of different types of organisations ranging from large pharmaceutical multinationals (e.g. E. Lilly, Janssen Pharmaceutica) or large chemical multinationals (e.g. Bayer, Solvay) to a smaller Belgian pharmaceutical company (SMB-Galephar). Other members belong to a governmental scientific institution in the health sector (Pasteur’s Institute), to the Scientific Institute of the Dutch Pharmacists and to a University department (System of mechanic production and metrology, ULg).
The project will be beneficial for the members of the users committee as well as for the scientific collaborators.
PROMOTERS
Jacques CROMMEN
Université de Liège
Institut de Pharmacie
C.H.U. Bât. B36
Avenue de l’Hôpital 1
B-4000 LIEGE 1
Tel: +32 4 366.43.46
Fax: +32 4 366.43.47
E-mail: jcrommen@ulg.ac.be
Désiré L. MASSART
Vrije Universiteit Brussel
Farmaceutische en Biomedische analyse
Laarbeeklaan 103
B-1090 BRUSSEL
Tel: +32 2 477.47.37
Fax: +32 2 477.47.35
E-mail: massart@vub.vub.ac.be
Jos HOOGMARTENS
Katholieke Universiteit Leuven
Laboratorium voor Farmaceutische Chemie en Analyse van Geneesmiddelen
Van Evenstraat 4
B-3000 LEUVEN
Tel: +32 16 32.34.42
Fax: + 32 16 32.34.48
E-mail: jos.hoogmartens@farm.kuleuven.ac.be
Norms and guidelines for the practical estimation of uncertainty in analytical measurements : final report
Brussels : Federal Science Policy, 2005 (SP1474)
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