A novel method for rapid determination of risperidone in human plasma using Reversed-Phase Liquid Chromatography with Ultra-Violet detection

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Dhouha Sahnoun
Emna Gaies
Syrine Ben Hammamia
Mouna Ben Sassi
Chaker Ben Salem
Riadh Daghfous
Sameh Trabelsi

Abstract

Aim: A simple and sensitive High-Performance Liquid Chromatographic (HPLC) method with UV detection is described for the quantitation of risperidone in human plasma, using bisoprolol as internal standard.


Methods: After sample alkalinization with 900 µl of NaOH, the test compounds were extracted from plasma using diethylether. The tubes were centrifuged twice and an evaporation to dryness under a gently stream of nitrogen at 50°C (~10 min) was done. 50 μl of the solution was injected into a C18 Nucleosyl analytical column (5 μm, 150×4.6 mm I.D). The mobile phase consisted of phosphate buffer (10 mM, pH 4.9 and 30% acetonitrile, (70:30, v/v), and was delivered at a flowrate of 1.0 ml/min. Results: The peaks were detected using a UV detector set at 279 nm and the total time for a chromatographic separation was about 8 min. This new method was validated for the concentration range 5–150 ng/ml. Mean recoveries were 92 % for risperidone. Intra- and inter-day relative standard deviations were less than 15% for our compound, while accuracy, expressed as percent error, ranged from 0.13 to 19 %. The limit of quantitation (LLOQ) was 3.23 ng/ml for the analyte.


Conclusion: The method shows good specificity with respect to commonly prescribed psychotropic drugs.

Keywords:

Risperidone, HPLC, Bisoprolol, Therapeutic drug monitoring, Pharmacokinetics

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Author Biography

Emna Gaies, Department of clinical pharmacology, National Center Chalbi Belkahia of Pharmacovigilance, Tunis, Tunisia.

National Center Chalbi Belkahia of Pharmacovigilance, Department of clinical pharmacology, Tunis, Tunisia.

References

  1. Raggi MA, Bugamelli F, Sabbioni C, Saracino MA, Petio C. HPLC-DAD determination of plasma levels of the antipsychotic risperidone and its main metabolite for toxicological purposes. J Sep Sci 2005; 28(3): 245‑50.
  2. Avenoso A, Facciolà G, Salemi M, Spina E. Determination of risperidone and its major metabolite 9-hydroxyrisperidone in human plasma by reversed-phase liquid chromatography with ultraviolet detection. J Chromatogr B Biomed Sci App 2000; 746(2): 173‑81.
  3. Hiemke C, Bergemann N, Clement H and al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: Update 2017. Pharmacopsychiatry 2018; 51: 9-62.
  4. Siva Selva Kumar M, Ramanathan M. Concurrent determination of olanzapine, risperidone and 9-hydroxyrisperidone in human plasma by ultra-performance liquid chromatography with diode array detection method: application to pharmacokinetic study. Biomed Chromatogr 2016; BMC 30(2): 263-8.
  5. Luo L, Liu X, Jin X and al. Simultaneous determination of skimmin, apiosylskimmin, 7-hydroxycoumarin and 7-hydroxycoumarin glucuronide in rat plasma by liquid chromatography-Orbitrap mass spectrometry and its application to pharmacokinetics. Biomed Chromatogr 2022; BMC 36(1): e5223.
  6. Murugan S, Elayaraja A, Niranjan B M, and al. Review on Method Development and Validation by Using Hplc. International Journal of Novel Trends in Pharmaceutical Sciences 2013; 3(4):78-81.
  7. Jones T, Van Breda K, Charles B, Dean AJ, McDermott BM, Norris R. Determination of risperidone and 9-Hydroxyrisperidone using HPLC, in plasma of children and adolescents with emotional and behavioural disorders. Biomed Chromatogr BMC 2009; 23(9):929-34.
  8. Čabovska B, Cox SL, Vinks AA. Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 852(1‑2): 497‑504.
  9. Nagasaki T, Ohkubo T, Sugawara K, Yasui N, Furukori H, Kaneko S. Determination of risperidone and 9-hydroxyrisperidone in human plasma by high-performance liquid chromatography: application to therapeutic drug monitoring in Japanese patients with schizophrenia. J Pharm Biomed Anal 1999; 19(3-4): 595-601.
  10. Aravagiri M, Marder SR, Wirshing D, Wirshing WC. Plasma concentrations of risperidone and its 9-hydroxy metabolite and their relationship to dose in schizophrenic patients: simultaneous determination by a high performance liquid chromatography with electrochemical detection. Pharmacopsychiatry 1998; 31(3): 102‑9.
  11. Locatelli I, Mrhar A, Grabnar I. Simultaneous determination of risperidone and 9-hydroxyrisperidone enantiomers in human blood plasma by liquid chromatography with electrochemical detection. J Pharm Biomed Anal 2009; 50(5):905‑10.
  12. LLerena A, Berecz R, Dorado P, Sanz de la Garza C, Norberto MJ, Caceres M, Determination of risperidone and 9-hydroxyrisperidone in human plasma by liquid chromatography: application to the evaluation of CYP2D6 drug interactions. Journal of Chromatography B 2003; 783: 213-19.