Plasma proteins chemical analysis

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

Most of the methods in use in clinical chemistry laboratories involve colorimetric analysis in fewer instances volumetric or gravimetric procedures are still retained. It is not the purpose of this review to enter into a discussion of the errors inherent in colorimetric, volumetric, and gravimetric analysis as such for a treatment of this subject the reader is referred to standard works on chemical analysis (e.g., V3). Instead, the review will be confined to those sources of error that are particularly likely to affect the work of a clinical laboratory. These errors arise mainly from the need to perform many analyses on large numbers of samples with a variable degree of urgency, and from the fact that most of these analyses have to be conducted on plasma or semm, which are viscous protein-rich fluids available only in restricted quantities (M12). 

B6. Becker, J., Higgins, G., and O Brien, J. R. P., Plasma proteins some chemical methods of fractionation starch gel electrophoretic analysis. Proc. Assoc. Clin. Biochem. 1, 83-84 (1961). 

Traditional wet-chemical procedures required serum or plasma proteins to be removed prior to further analysis this was achieved by precipitation, usually with acids such as trichloracetic acid or metal ions, e.g., zinc sulfate. If organic acid extraction were to be used, this would also precipitate proteins. Such methods are scarcely used in routine practice. Automated procedures can readily be adapted to determine colorimetric endpoint or rates of reaction the avoidance of protein interference is more difficult (see the section Large-capacity analyzers ). 

The principle concern of MMPs for chemical structures is how the trade-off between specificity and general trend is achieved [66]. A very specifically defined environment for a chemical transformation results in a much narrower dataset for statistical analysis. The extracted trend might then be clearer for this particular problem, but based on a smaller dataset. Hence, any further generalization might be difficult. If on the other hand, the molecular context is completely nnconstrained, then the effect of a particular substitution is likely to reflect only simple trends, mainly related to lipophilicity as one of the cardinal properties in medicinal chemistry [62, 66, 67]. The simpler the property for MMP analysis is, the more likely is a direct link to molecular structure, as shown by Leach et al. in their study on solnbihty and plasma protein binding [62]. Typical control parameters for stable MMP trends are thus related to a minimum number of matched pairs for analysis and a certain degree of structural diversity upon all members in a dataset, excluding of conrse those linked by a molecular transformation [71]. 

Many other types of solid phase adsorbents, including those based on conventional and specialty materials like restricted access media (RAM), can increase analysis speed and improve assay performance. These types of materials, also known as internal reversed-phase packings, are especially useful for assaying target compounds in biological samples such as serum and plasma. They are chemically modified porous silicas that have hydrophilic external surfaces and restricted-access hydrophobic internal surfaces. The ratio of interior to external surface areas is large. Macromolecules such as proteins cannot enter the pores of the RAM (they are excluded from the hydrophobic internal surface) and they elute quickly through the column. However, the smaller analyte molecules that can enter the pores are retained via interactions with the hydrophobic bonded phase within... 

The primary technique for the surface analysis of polymers (3-4), including biomaterials (5-6) over the last decade has been X-ray photoelectron spectroscopy (XPS or GSCA). The technique has been employed to study the interfacial orientation, contamination, modifications, eg plasma treatments (7) and protein deposition on biomedical polymers ( ). While XPS provides valuable multi-element (except hydrogen) and chemical state information, the limited range... 

Hou W, Watters JW, McLeod HL (2004) Simple and rapid docetaxel assay in human plasma by protein precipitation and high-performance liquid chromatography-tandem mass spectrometry. Journal of Chromatography B 804 263-267 Schuhmacher J, Zimmer D, Tesche F, Pickard V (2003) Matrix effects during analysis of plasma samples by electrospray and atmospheric pressure chemical ionization mass spectrometry practical approaches to their elimination. Rapid Communications in Mass Spectrometry 17 1950-1957 Shah PW (2001) Guidance for Industry Bioanalytical Method Validation U.S. Department of Health and Human Services, Food and Drug Administration... 

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