title: Determination of haloperidol and reduced haloperidol in human serum by liquid chromatography after fluorescence labeling based on the Suzuki coupling reaction.
abstract: 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 H(2)O (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.
authors.affiliation: Graduate School of Biomedical Sciences, Course of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kishikawa
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Hamachi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Imamura
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ohba
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nakashima
authors.forename: Yashuhiro
authors.initials: Y
authors.lastname: Tagawa
authors.forename: Naotaka
authors.initials: N
authors.lastname: Kuroda
mesh_terms: D001896:Boron Compounds / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring; D005260:Female; D005453:Fluorescence; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012016:Reference Values; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000097:blood*; D012680:Sensitivity and Specificity
chemical_list: D001896:Boron Compounds; C040692:4-(4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl)-1-(4-fluorophenyl)-1-butanol; C035757:diphenylborate; D006220:Haloperidol