Biomarkers quality control

In subsequent chapters, we provide an overview of SPMD fundamentals and applications (Chapter 2) the theory and modeling which includes the extrapolation of SPMD concentrations to ambient environmental concentrations (Chapter 3) study considerations such as the necessary precautions and procedures during SPMD transport, deployment, and retrieval (Chapter 4) the analytical chemistry and associated quality control for the analysis of SPMD dialysates or extracts (Chapter 5) a survey and brief description of bioassays-biomarkers used to screen the toxicity of SPMD environmental extracts (Chapter 6) discussions on how HOC concentrations in SPMDs may or may not relate to similarly exposed biomonitoring organisms (Chapter 7) and selected examples of environmental studies using SPMDs (Chapter 8). In addition, two appendices are included which provide... 

Quality assurance and quality control of biomarker data get far more attention than whether biomonitoring communication goals are achieved and why (Balch and Sutton 1995), despite the importance of both issues. The committee suggests practical ways to improve biomonitoring evaluation below. 

As described above TMAs are created to answer specific questions. It is important to clearly define this question at the outset. The question will help define the number of cases and cores that need to be used in the generation of the TMA. For example a TMA containing 20 cases might be sufficient for routine quality control/ assessment but is not enough for biomarker assessment. 

The effects of the appropriate environmental matrices (soil, water, air, biological - for biomarker or exposure assessment studies) on assay performance must be well characterized and documented. The SOP must also include the degree of quality control necessary to ensure the satisfactory performance of the method. Quality control procedures must address the required sample preparation steps, reagent stability, instrumentation, data handling and analysis. In many immunoassay SOPs that the EPA has reviewed, quality control is totally lacking or minimally addressed particularly for the sample preparations. The Agency can provide direction on what is an appropriate degree of quality control based on the objective of the method. 

Mattsson N, Andreasson U, Persson S, Carrillo MC, Collins S, Chalbot S et al (2013) CSF biomarker variability in the Alzheimer s Association quality control program. Alzheimers Dement 9 251-261... 

In the pharmaceutical industry, the techniques are being used to examine off-target effects particularly for the early identification of toxicity. MOA can be studied through metabolomics and can also be used as a quality control tool for complex mixtures such as foods or herbal medicines. Similarly, the tools and expertise of natural products chemists are essential in metabolomics, particularly in biomarker discovery (see also Volume 9). Biomarker discovery via untargeted metabolomics can lead to metabolite signatures (nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), etc.) that are not present in current metabolomics databases. This is particularly true for plant secondary metabolism studies and nonmammalian metabolites. Structure elucidation then becomes critical to understanding the metabolomics results and for biomarker development. 

In sununary, given the nature of the reporting of the quality-control data in these three studies, it is difficult to assess the analytical error inherent in the biomarker concentrations and ultimately in the dose-response relationships. It is also difficult to quantitatively or qualitatively compare the extent of analytical error in these studies. Some concern, however, is warranted with respect to the analytical error inherent in the New Zealand study. The extent to which that error might affect the interpretation of the dose-response relationship based on the New Zealand study is not clear. 

In-study validation entails the routine monitoring of the quality control samples to determine whether the analytical method is performing consistently over time and whether data from a particular plate or run are acceptable. In addition, especially for biomarker assays, evaluation of parallelism using incurred samples is carried out to confirm the validity and suitability of the reference standard. 

Sweep, F.C., Fritsche, H.A., Gion, M., Klee, G.G., and Schmitt, M. (2003) Consider ations on development, validation, application, and quality control of immuno(metric) biomarker assays in clinical cancer research an EORTC NCI working group report. International Journal of Oncology, 23, 1715 1726. 

Lactate is produced as a metabolic intermediate in humans and is a biomarker of human performance levels (Shah et ah, 2007). In the food industry, sodium, potassium, and calcium lactates (E number E325, E326, and E327, respectively) have been approved as food additives, and are used to regulate pH and as preservatives and flavoring agents. Lactate can also be used as a marker of fermentation (Avramescu et al., 2002) and a chemical indicator of flavor (Hemmi et al., 1995). Thus, determination of lactate concentrations is important not only for food process control but also for quality control of foods. In this chapter, we review flow injection analysis (FIA) for lactate determinations. 

Encouraged by this spectral reproducibility, we focused our efforts on the particularly challenging problem of distinguishing bacterial strains by MALDI MS. We developed a modified correlation approach22 that relies on two fundamental qualities of bacterial mass spectra. First, because different bacterial strains of the same species have substantial, if not complete, genetic overlap, most of the protein masses observed with two different strains will be identical. This feature limits the value of the biomarker approach that is commonly used to differentiate bacteria species. Second, as just noted, closely controlled sample preparation and mass analysis procedures can result in highly reproducible results.22 The modified correlation approach takes advantage of subtle, yet reproducible, differences in mass spectra obtained from dif-... 

---