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Determination of haloperidol and reduced haloperidol in human serum by liquid chromatography after fluorescence labeling based on the Suzuki coupling reaction

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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 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.

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References

  1. Yamaguchi M, Ishida J (1999) In: Toyo’oka T (ed) Modern derivatization methods for separation sciences. Wiley, Chichester, pp 99–108

    Google Scholar 

  2. Nakashima K (2003) Biomed Chromatogr 17:83–95

    Article  CAS  Google Scholar 

  3. Fukushima T, Usui N, Santa T, Imai K (2003) J Pharm Biomed Anal 30:1665–1687

    Article  Google Scholar 

  4. Uchiyama S, Santa T, Okiyama N, Fukushima T, Imai K (2001) Biomed Chromatogr 15:295–318

    Article  CAS  Google Scholar 

  5. Kuroda N, Sugihara S, Sugihara Y, Wada M, Kishikawa N, Ohba Y, Nakashima K (2005) J Chromatogr A 1066:119–125

    Article  CAS  Google Scholar 

  6. Miyaura N, Suzuki A (1995) Chem Rev 95:2457–2483

    Article  CAS  Google Scholar 

  7. Suzuki A (1999) J Organomet Chem 576:147–168

    Article  CAS  Google Scholar 

  8. Santamaria B, Perez M, Montero D, Madurga M, de Abajo FJ (2002) Eur Psychiatry 17:471–476

    Article  Google Scholar 

  9. Lane HY, Lin HH, Hu OY, Chen CC, Jann MW, Chang WH (1997) Prog Neuropsychopharmacol Biol Psychiatry 21:299–311

    Article  CAS  Google Scholar 

  10. Korpi ER, Kleinman JE, Costakos DT, Linnoila M, Wyatt RJ (1984) Brain Res 11:259–269

    CAS  Google Scholar 

  11. Lane HY, Chang WH, Chang YC, Hu OYP, Lin HN, Chang WH, Jann MW, Hu WH (1997) Psychiatry Res 72:127–132

    Article  CAS  Google Scholar 

  12. Walter S, Bauer S, Roots I, Brockmöller J (1998) J Chromatogr B 720:231–237

    Article  CAS  Google Scholar 

  13. Pan L, Rosseel MT, Belpaire FM (1998) Ther Drug Monit 20:224–230

    Article  CAS  Google Scholar 

  14. Arinobu T, Hattori H, Iwai M, Ishii A, Kumazawa T, Suzuki O, Seno H (2002) J Chromatgr B 776:107–113

    Article  CAS  Google Scholar 

  15. Marquet HH, Verneuil B, Lotfi H, Dupuy JL, Pénicaut B, Lachâtre G (1997) J Chromatgr B 688:275–280

    Article  Google Scholar 

  16. Fujii T, Hatanaka K, Sato G, Yaui Y, Arimoto H, Mitsutsuka (1996) J Chromatgr B 687:395–403

    Article  CAS  Google Scholar 

  17. Fukuda R (2000) Prog Neuropsychopharmacol Biol Psychiatry 24:1299–1318

    Article  CAS  Google Scholar 

  18. Wu AB, Huan MC, Ho HO, Yeh GC, Sheu MT (2004) Biomed Chromatogr 18:443–449

    Article  CAS  Google Scholar 

  19. Kuroda N, Kawazoe K, Nakano H, Wada M, Nakashima K (1999) Luminescence 14:361–364

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Graduate School of Biomedical Sciences, Course of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan

    Naoya Kishikawa, Chiyuki Hamachi, Yoshihito Ohba, Kenichiro Nakashima & Naotaka Kuroda

  2. Tagawa Sanatorium, 1-1-2 Nishiki, Nagasaki, 852-8045, Japan

    Yoshihiro Imamura & Yashuhiro Tagawa

Authors
  1. Naoya Kishikawa
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  2. Chiyuki Hamachi
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  3. Yoshihiro Imamura
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  4. Yoshihito Ohba
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  5. Kenichiro Nakashima
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  6. Yashuhiro Tagawa
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  7. Naotaka Kuroda
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Correspondence to Naotaka Kuroda.

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Kishikawa, N., Hamachi, C., Imamura, Y. et al. Determination of haloperidol and reduced haloperidol in human serum by liquid chromatography after fluorescence labeling based on the Suzuki coupling reaction. Anal Bioanal Chem 386, 719–724 (2006). https://doi.org/10.1007/s00216-006-0755-0

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  • DOI: https://doi.org/10.1007/s00216-006-0755-0

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