Analytical Pitfalls with Tricyclic and Newer Antidepressants in Biological Samples
With antidepressants and their active metabolites there are analytical complications: low concentrations; surface adsorptivity during extraction; chromatographic co-elution with other drugs and contaminants; and uncertainty about survival during storage and chromatography. Stability experience with the tricyclics does not hold for newer antidepressants. Thus, bupropion (but not its three major metabolites) showed temperature- and pH-dependent log-linear degradation in plasma. The importance of validating extraction techniques for each sample type is exemplified by trazodone, which was extractable from plasma by methyl-t-butyl ether but required isoamyl alcohol/hexane for brain tissue extraction to obviate emulsions and include an active metabolite. For cyclic antidepressants in general, sources of inaccuracy include the preparation of non-methanolic stock solutions, mode of rendering alkaline, standard-curve determination with homogenates of the tissue concerned, and HPLC validation with a converse-polarity system, e.g. NP instead of RP. Other points of practice are also discussed, e.g. sample collection, in the context of inter-laboratory differences in assay performance.
KeywordsIsoamyl Alcohol Cyclic Antidepressant Brain Tissue Extraction Analytical Complication Single Extraction Method
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