Both loperamide and its major
metabolite, N-desmethylloperamide, were isolated by liquid–liquid extraction into n-butyl chloride from alkalinized samples. Extracts were analyzed by liquid chromatography–electrospray-mass spectrometry in selected-ion-monitoring mode. Rapid separation of the drug, metabolite, and internal standard (diphenoxylate) was achieved using a high-resolution C18 column with 1.8-µm particle diameter. The mobile phase consisted of 0.