Determination of haloperidol and reduced haloperidol in human serum by liquid chromatography after fluorescence labeling based on the Suzuki coupling reaction
Determination of haloperidol and reduced haloperidol in human serum by liquid chromatography after fluorescence labeling based on the Suzuki coupling reaction
复制标题
DOI：
10.1007/s00216-006-0755-0
复制
发表时间：
2006-10-01
影响因子：
4.3
通讯作者：
Kuroda, Naotaka
中科院分区：
文献类型：
--
作者：
Kishikawa, Naoya;Hamachi, Chiyuki;Kuroda, Naotaka
建立了同时测定人血清中氟哌啶醇（HP）及其代谢物还原氟哌啶醇（RHP）的高效液相色谱-荧光检测法。利用Suzuki偶联反应将HP和RHP转化为荧光化合物4-（4，5-二苯基-1H-咪唑-2-基）苯基硼酸（DPA）。用正己烷和异戊醇（99：1，v/v）的混合液液-液萃取法从人血清中提取HP和RHP，随后用DPA反应标记。HP和RHP的DPA衍生物在硅胶柱上以含有三乙胺和乙酸的乙腈和水（90：10，v/v）的混合物作为移动的流动相进行分离。该方法可以灵敏地检测人血清中的HP和RHP，检测限（信噪比为3）分别为0.22和0.20 ng/mL。通过分析接受HP治疗的精神分裂症患者的血清样品，证明了该方法用于治疗药物监测（TDM）的适用性。
A simultaneous method for the determination of haloperidol (HP) and its metabolite, reduced haloperidol (RHP), in human serum was developed by means of high-performance liquid chromatography (HPLC) with fluorescence detection. Suzuki coupling reaction with a fluorescent arylboronic acid, 4-(4,5-diphenyl-1H-imidazol-2-yl)phenylboronic acid (DPA), was employed to convert HP and RHP into highly fluorescent compounds. HP and RHP were extracted from human serum by liquid-liquid extraction with a mixture of n-hexane and isoamyl alcohol (99:1, v/v) and subsequently labeled by reaction with DPA. Separation of DPA derivatives of HP and RHP was performed on a silica column with a mixture of acetonitrile and H2O (90:10, v/v) containing triethylamine and acetic acid as a mobile phase. The proposed method allowed sensitive detection of HP and RHP in human serum with a detection limit (at a signal to noise ratio of 3) of 0.22 and 0.20 ng/mL, respectively. The applicability of the method for therapeutic drug monitoring (TDM) was demonstrated by analyzing human serum samples from schizophrenic patients receiving HP.