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SummaryAn automated microbore, liquid chromatographic method with column-switching was developed for the determination of clomipramine from human plasma samples. After direct injection of samples (60#L), plasma proteins and clomipramine were separated in size-exclusion mode using 20 % acetonitrile in 20 mM phosphate buffer (pH 7.0) on Capcell Pak MF Ph-1 precolumn (10 x 4mm I.D.). By valve switching, a fraction containing clomipramine was directed to an intermediate column for subsequent main separation on a microbore Cls column (250 x 1.5 mm I.D.) using 50 % acetonitrile in 20 mM phosphate buffer (pH 2.5) at 0.1 mL min -1. The method was advantageous for rapidity (total analysis time: 15min), reproducibility (C.V. < 4.8 %), and increased sensitivity (1 ng mL-1). The linearity of response was good (r e -> 0.999) over the concentration range 1-250 ng mL -1.