Fecal samples, metabolite analysis

Mass Balance Studies. Pharmacokinetic mass balance studies apply unlabeled, stable isotopes or radiolabeled compounds to study the extent of absorption and first-pass metabolism, distribution, and excretion of a given compound. In the microdosing approach, a C-labeled compound is administered to human volunteers at doses from as low as one microgram blood, urine, and fecal samples are collected over time and analyzed for C content by accelerator mass spectroscopy to determine half-life, plasma AUC, and maximal concentration (Cmax)- However, these methods are not very popular even when very low doses of radioactivity are involved. Highly sensitive, and more readily available, tech-niques for separation and analysis (e.g., LC-MS, LC-MS/MS) are frequently used alternatives that enable pharmacokinetic investigations and metabolite profiling of nonradiolabeled compounds. 

Plasma, urine, bile, and fecal samples are obtained following a single oral or IV administration of a radiolabeled drug to rats, mice, rabbits, dogs, monkeys, or humans. In general, collection times for blood samples are chosen based on the PK parameters of the drug, such as ti/2, Cmax (at least four time points, e.g., 1, 4, 12, 24 h, for metabolite profiling and multiple time points for PK analysis). Urine and feces are collected at specific intervals from zero hours to the end of the study, usually from 0 to 168 h. 

Yang, R. S. H., F. Coulston, and L. Goldberg Chromatographic methods for the analysis of hexachlorobenzene and possible metabolites in monkey fecal samples. J. Assoc. Official Anal. Chemists 58,1197 (1976). 

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