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The effects of various tissue preservation buffers on cytochrome P450 (P450)-mediated activities of microsomes prepared from fresh surgical liver samples were examined. Two individual human liver samples were obtained, and three portions of each were preserved in one of three solutions: phosphate buffer, Krebs-Heinseleit solution, or University of Wisconsin solution. Microsomes were prepared within 24 h, 3 days, and 7 days after the resection of the samples. Marker P450 activities were measured. Liver microsomes prepared within 24 h displayed similar ethoxyresorufin O-deethylation, bufuralol 1'-hydroxylation (BF 1'-OH), and chlorzoxazone 6-hydroxylation activities in all preservation solutions, whereas S-mephenytoin 4'-hydroxylation and midazolam 1'-hydroxylation activities displayed some variation depending on the preservation buffer used. Most of the marker P450 activities were stable for 3 days after removal from surgical patients and declined at 7 days; however, a decline in BF-1'OH activity was observed even at day 3. These results suggest P450-specific activity depends on the method by which human liver samples are preserved. Moreover, the results of these studies establish the minimum tissue preservation criteria that, when met, qualify the drug disposition data generated from subcellular fractions derived from a particular surgical tissue sample.