Mizuno Yasushi, Sato Keizo, Sano Toshiyuki, Kurihara Rina, Kojima Takashi, Yamakawa Yoshinori, Ishii Akira, Katsumata Yoshinao
Department of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Leg Med (Tokyo). 2002 Dec;4(4):207-16. doi: 10.1016/s1344-6223(02)00051-2.
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-R(1)+CH(2), R(1), M-R(1) 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-R(1)-CH(3), M-R(1)-CH(2)CH(3) or M-R(1)-(CH(3))(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 microg 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.
吩噻嗪类药物作为抗精神病药物被广泛使用；有些还用作抗组胺药。这些化合物在临床和法医毒理学中很重要。已发现17种具有重侧链结构的吩噻嗪化合物可用高效液相色谱/快原子轰击质谱法（HPLC/FAB-MS）检测。将这些化合物的标准样品置于我们的HPLC/FAB-MS系统中；通过正离子和负离子模式获得它们的质谱。还分析了两名患者血清样本中的四种典型吩噻嗪。所有17种吩噻嗪在色谱图上都得到了充分分离。在正离子模式下，所有的基峰都是准分子离子；观察到的主要碎片离子为M-R(1)+CH(2)、R(1)、M-R(1)和M+H+Gly。在负离子模式下，对于含有氯的氯丙嗪、丙氯拉嗪和奋乃静这三种化合物，基峰为Cl。对于其他化合物，基峰为M-R(1)-CH(3)、M-R(1)-CH(2)CH(3)或M-R(1)-(CH(3))(2)离子。我们在所有化合物中都观察到了M+H离子，不过其离子强度各不相同（3-74%）。还获得了两名患者提取血清样本中四种化合物及其代谢物的光谱和质量色谱图。吩噻嗪类药物在正离子模式下的柱上近似检测限小于1 ng，在负离子模式下约为1 μg。我们已成功使用我们的HPLC/FAB-MS系统在体液的治疗浓度下鉴定和表征了17种吩噻嗪化合物。本方法在法医毒理学实践中将会很有用。
