Analyses of butyrophenones and their analogues in whole blood by high-performance liquid chromatography–electrospray tandem mass spectrometry

Five butyrophenones and two analogues contained in human whole blood have been analyzed by high-performance liquid chromatography (HPLC)–electrospray (ES)-tandem mass spectrometry (MS). All compounds gave the base peaks due to [M+1]+ by HPLC–ES-single MS. The product ions formed from each quasi-molecular ion by HPLC–ES-tandem MS showed the base peaks at m/z 165 for four compounds. The mass chromatography of HPLC–ES-tandem MS showed much higher sensitivity than that of HPLC–ES-single MS for all drugs spiked to whole blood. Therefore, regression equations, detection limits, recovery rates and precision were studied for haloperidol, bromperidol and floropipamide spiked to human whole blood by means of mass chromatography of HPLC–ES-tandem MS. The three compounds showed good linearity in the range of 0.2–0.8 ng/ml with a detection limit of about 0.1 ng/ml. Recoveries of the three compounds spiked to whole blood (0.2 and 0.8 ng added to 1 ml whole blood) were 23.6–81.2%; the coefficients of intra- and inter-day variations were 8.4–10.4 and 14.5–17.5%, respectively. The three compounds in whole blood could be actually determined 3 and 6 h after oral administration of 1 mg each of haloperidol and bromperidol, and 10 mg of floropipamide in a volunteer.