Haloperidol and its two metabolites, reduced haloperidol and 4-(4-Chlorophenyl)-4-hydroxypiperidiene (CPHP), contained in human plasma and urine were analyzed by using a new type of HPLC column (MSpak GF-310) for direct injection of biological samples without complicated pretreatment, and they were determined by means of high-performance liquid chromatography (HPLC)-mass spectrometry (MS). The regression equations of haloperidol, reduced haloperidol and CPHP showed good linearity in the range of 10-800 ng/ml, 15-800 ng/ml and 400-800 ng/ml, respectively, for both plasma and urine. Their detection limits were 5 ng/ml, 10 ng/ml and 300 ng/ml, respectively, for both plasma and urine. We would conclude that the present method was sensitive enough for detection and determination of toxic level for haloperidol in blood, and this approach appears to have a high-potential method for rapid drug analysis from biological samples including biopolymer such as protein.