Fundamentals of Analytical Toxicology. Robin Whelpton
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Название: Fundamentals of Analytical Toxicology

Автор: Robin Whelpton

Издательство: John Wiley & Sons Limited

Жанр: Биология

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isbn: 9781119122371

isbn:

СКАЧАТЬ occupational history, if available. Decide the priorities for the analysis Analytical Perform the agreed analysis Post-analytical Interpret the results in discussion with the physician looking after the patient or the pathologist. Perform additional analyses, if indicated, using either the original samples, or further samples from the patient. Save any unused or residual samples for possible future use

       1.3.1 Samples and sampling

      In analytical toxicology, clinical chemistry, and related fields, the words ‘sample’ and ‘specimen’ are used to denote a portion of a body fluid, tissue, incubation medium, etc. obtained under defined conditions. The samples encountered may range from relatively pure solutions of a drug to a piece of putrefying tissue. Liquids, such as blood, oral fluid (principally saliva), urine, and cerebrospinal fluid (CSF), are generally easier to sample and to analyze than solids and semi-solids, which require homogenization or digestion prior to analysis.

      Blood plasma or serum is used in clinical work if quantitative measurements are needed in order to assess dosage or monitor treatment as in TDM. Urine is commonly used in qualitative work such as substance misuse screening because collection is non-invasive and the concentrations of many drugs and their metabolites tend to be higher than in blood, thereby facilitating analyte detection. Further aspects related to samples and sampling are discussed in Chapter 2.

       1.3.2 Choice of analytical method

      In responding to a given analytical problem, many factors must be considered. It may seem self-evident that the method used should be appropriate for the intended analysis. In practice, the choice of method depends on several factors. These include (i) the circumstances under which an analysis is requested (i.e. the question being asked), (ii) the speed with which the result is required, (iii) the sample to be analyzed, (iv) the nature of the analyte (if known), (v) the expected concentration of any analyte(s), (vi) the time available for the analysis, (vii) the apparatus available, (viii) the existence of a validated method in the laboratory, and (ix) the training and experience of the analyst.

      

       1.3.3 Method validation and implementation

      A method must possess adequate sensitivity for the task in hand. The limit of sensitivity is a term often used to describe the limit of accurate measurement, but this is better defined as the lower limit of quantification (LLoQ). The limit of detection (detection limit) is a better term for limit of sensitivity. Whatever terminology is used, assessing the presence or absence of a compound at the limit of assay sensitivity is always difficult and ideally reporting a positive finding in such circumstances requires corroboration from other evidence.

Number of chiral centres If n = number of optical centres there will be 2nisomers. Molecules with two optical centres can exist as four molecules: two diasteromers (diastereoisomers), each consisting of two enantiomers, i.e. there are two pairs of enantiomers. The exception to this is if two molecules have a plane of symmetry (a plane that divides a molecule into two parts, each a mirror image of the other) and therefore cancel out their net optical rotation. In such cases they are known as meso forms
Nomenclature Enantiomers possess a unique property in that they rotate plane-polarized light to the same extent, but in opposite directions. This is the basis of the (+)/(–) or d/l notation, the former being preferred as it avoids confusion with D/L, however it does not unequivocally distinguish between enantiomers because some molecules may change rotation on forming salts. The notation tells nothing about the absolute configuration, i.e. the spatial arrangement, of the atoms
Rotation of plane polarized light