title: Quantitative assessment of the binding of acetaminophen metabolites to mouse liver microsomal phospholipid.
abstract: Phospholipids were quantitatively extracted from microsomes and separated by an h.p.l.c. gradient system with a solvent mixture of n-hexane/n-propanol/water/acetic acid. In a model reaction using horseradish peroxidase/H2O2 in order to activate acetaminophen and inactivated microsomes as target, a covalent binding of 10 nmol drug metabolite per mg microsomal lipid was found. In isolated intact microsomes from methylcholanthrene-pretreated male albino mice, a binding of 0.1 nmol acetaminophen metabolite per mg phospholipid was determined while the binding of metabolites to protein amounted to 3 nmol/mg. The results demonstrate that in mouse liver microsomes metabolizing acetaminophen, about one out of 10(4) phospholipid molecules is modified.
mesh_terms: D000082:Acetaminophen / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006735:Horseradish Peroxidase / Q000378:metabolism; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
chemical_list: D008563:Membrane Lipids; D008565:Membrane Proteins; D010743:Phospholipids; D000082:Acetaminophen; D006735:Horseradish Peroxidase