Biological matrices, drugs

With strata-X, procainamide elutes off under any conditions including >25% methanol in the solvent. With strata-X-CW, the drug can be eluted off under both acidic and basic conditions with >40% methanol content in the solvent. As with strata-X, the drug is eluted off under acidic or basic conditions with >50% methanol using strata-X-AW. Overall, strata-X-C is the best option for procainamide from a biological matrix. 

A typical application of GC to the determination of a drug in plasma is in the determination of the anti-epileptic drug valproic acid after solid phase extraction (see Ch. 15) by GC with flame ionisation detection. In this procedure, caprylic acid, which is isomeric with valproic acid, was used as an internal standard. The limit of detection for the drug was 1 pg/ml of plasma. The trace shown in Figure 11.25 indicates the more extensive interference from background peaks extracted from the biological matrix which occurs in bioanalysis compared to the quality control of bulk materials. 

Selective detectors tend to be employed where the analyte is present in small amounts in a complex matrix such as in bioanalytical procedures where components extracted from the biological matrix along with the analyte can cause interference. Some formulated compounds have only very poor chromophores - these include sugars, lipids, surfactants, amino acids and some classes of drugs, e.g. a number of anticholinergic drugs lack chromophores. In these cases an alternative to UV detection has to be employed. 

Analyte a specific chemical moiety being measured, which can be intact drug, biomolecule, or its derivative, metabolite, and/or degradation product in a biological matrix. 

Figure 6.11. Mass defect plots of human biological matrices obtained from high-resolution LC-MS data (a) plasma, (b) bile, (c) feces, and (d) urine. LC-MS data from each biological matrix were combined into one spectrum to generate the mass defect plots, (e) Mass defect plot of 115 marketed drugs. The dotted circle in each plot represents the dense population of the mass defects of 115 marketed drugs.

Any toxicological analysis involves two broad steps the first is extraction of the toxic agent from the biological matrix and the second is identification and quantitation of the isolated material. There are very few useful tests which can be applied directly to body fluids. Exceptions are urine screening tests for salicylate, ethclorvynol, and phenothiazine drugs. 

Vessman, J. (1980). Modifications in the work-up procedure for drugs due to the biological matrix. In Trace Organic Sample Handling (E. Reid, ed.), pp. 284-290. Halsted, New York. 

Measurement of a metabolite may be preferred when concentrations of the parent drug are too low to allow reliable analytical measurement in blood, plasma or serum for an adequate length of time, or when the parent compormd is unstable in the biological matrix. 

Lopez, L.L. Yu, X. Cui, D. Davis, M.R. Identification of Drug Metabolites in Biological Matrixes by Intelligent Automated Liquid Chromatography/Tandem Mass Spectrometry, Rapid Commun. Mass Spectrom. 12(22), 1756-1760 (1998). 

For pharmaceutical applications, the term bioanalysis refers to quantitative determination of a drug or its metabolites in a biological matrix. Although this term has traditionally been used to describe the analysis of in vivo samples (i.e., plasma or serum), current use of the term encompasses a broader range of applications that include the analysis of in vitro samples. Under this broader dehnihon, possible bioanalytical sample types can range anywhere from transport media to tissue homogenate. 

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