Technical Abstract: A high-performance liquid chromatography (HPLC) method was developed for measuring the concentrations of clovamide-type phenylpropenic acid amides (N-caffeoyldopamine and N-caffeoyltyramine) in cell and plasma samples. The HPLC separation of N-caffeoyldopamine and N-caffeoyltyramine was performed on a Nova-Pak C18 column (stationary phase) using an isocratic buffer (mobile phase) with a coulometric electrochemical detector with four electrode channels. Using the HPLC method, N-caffeoyldopamine and N-caffeoyltyramine could be detected with fine peak resolutions at respective retention times (4.5 and 6.7 min). The calibration curves for N-caffeoyldopamine and N-caffeoyltyramine were linear over the ranges 0.1 and 100 microM, and their lower limit of detection was as little as 100 fmol. For quantifying N-caffeoyldopamine and N-caffeoyltyramine in cell and plasma samples, the samples were extracted with methods providing more than 95% recoveries. After the extractions, N-caffeoyldopamine and N-caffeoyltyramine were analyzed with same sensitivity, peak resolutions, and retention times using the HPLC method. This HPLC method also enabled determination of the concentrations of N-caffeoyltyramine in mice plasma samples collected at 15, 30, 45, 60, and 70 min after the oral administration of N-caffeoyltyramine (0.5 mg and 2 mg/30 g body weight). This HPLC method, with an electrochemical detector, provides a sensitive and reproducible method for quantifying N-caffeoyldopamine and N-caffeoyltyramine in biological samples with superb detection limits, fine peak resolutions, and discrete retention times.