Identification and characterization of 17 phenothiazine compounds by capillary high-performance liquid chromatography/fast atom bombardment mass spectrometry.

Phenothiazines are widely prescribed as neuroleptics; some are used as antihistaminics. These compounds are important in clinical and forensic toxicology. Seventeen phenothiazine compounds with heavy side chain structures have been found to be detectable by high-performance liquid chromatography/fast atom bombardment-mass spectrometry (HPLC/FAB-MS) method. Authentic samples of the compounds were subjected to our HPLC/FAB-MS system; their mass spectra were obtained by positive and negative modes. Four typical phenothiazines, in the serum samples of two patients, were also analyzed. All 17 phenothiazines were sufficiently separated on the chromatogram. In the positive mode, all the base peaks were quasimolecular ions; their main fragment ions observed were [M−R1+CH2]+, [R1]+, [M−R1]+ and [M+H+Gly]+. In the negative mode, the base peaks were [Cl]− for chlorpromazine, prochlorperazine and perphenazine, three compounds containing chloride. For the other compounds, they were [M−R1−CH3]−, [M−R1−CH2CH3]− or [M−R1−(CH3)2]− ions. We observed [M+H]− ions in all the compounds, however, the ir intensities were variable (3–74%). The spectra and mass chromatograms of four compounds and their metabolites in the extracted serum samples from two patients, were also obtained. The approximate detection limits for phenothiazines were less than 1 ng on-column in the positive mode, and about 1 μg on-column in the negative mode. We have succeeded in the identification and characterization of 17 phenothiazine compounds at therapeutic concentrations in body fluids using our HPLC/FAB-MS system. The present method would be useful in forensic toxicological practice.