Similar articles

Abstract: This study presents a rapid, specific and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of risperidone (RIS) in human serum using paroxetine as an internal standard (IS). An Alltima-C18 column (2.1 mm×100 mm, 3 μm) and a mobile phase consisting of 0.1% formic acid-acetonitrile (40:60, v/v) were used for separation. The analysis was performed by selected reaction monitoring (SRM) method, and the peak area of the m/z 411.3→191.1 transition for RIS was measured versus that of the m/z 330.1→192.1 transition for IS to generate the standard curves. The assay linearity of RIS was confirmed over the range 0.25~50.00 ng/ml and the limit of quantitation was 0.05 ng/ml. The linear range corresponds well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations were 1.85%~9.09% and 1.56%~4.38%, respectively. The recovery of RIS from serum was in the range of 70.20%~84.50%. The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test versus reference products) in 18 healthy male Chinese volunteers. The result suggests that two formulations are bioequivalent.

[1] Aravagiri, M., Marder, S.R., 2000. Simultaneous determination of risperidone and 9-hydroxyrisperidone in plasma by liquid chromatography/electrospray tandem mass spectrometry. J. Mass Spectrom., 35(6):718-724.

[2] Aravagiri, M., Marder, S.R., Wirshing, D., Wirshing, W.C., 1998. 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, 31(38):102-109.

[3] Balant-Gorgia, A.E., Gex-Fabry, M., Genet, C., Balant, L.P., 1999. Therapeutic drug monitoring of risperidone using a new, rapid HPLC method: Reappraisal of interindividual variability factors. Ther. Drug Monit., 21(1):105-115.

[4] Bhatt, J., Subbaiah, G., Singh, S., 2006. Liquid chromatography/tandem mass spectrometry method for simultaneous determination of risperidone and its active metabolite 9-hydroxyrisperidone in human plasma. Rapid Commun. Mass Spectrom., 20(14):2109-2114.

[5] Cabovska, B., Cox, S.L., Vinks, A.A., 2007. Determination of risperidone and nantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS. J. Chromatogr. B, 852(1-2):497-504.

[6] Flarakos, J., Luo, W., Aman, M., Svinarov, D., Gerber, N., Vouros, P., 2004. Quantification of risperidone and 9-hydroxyrisperidone in plasma and saliva from adult and pediatric patients by liquid chromatography-mass spectrometry. J. Chromatogr. A, 1026(1-2):175-183.

[7] Huang, M.L., van Peer, R., Woestenborghs, R., de Coster, R., Heykants, J., Jansen, A.A., 1993. Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. Clin. Pharmacol. Ther., 54(3):257-268.

[8] Kousoulos, C., Dotsikas, Y., Yannis, L., Loukas, Y.L., 2007. Turbulent flow and ternary column-switching on-line clean-up system for high-throughput quantification of risperidone and its main metabolite in plasma by LC-MS/MS application to a bioequivalence study. Talanta, 72(2):360-367.

[9] Mannens, G., Huang, M.L., Meuldermans, W., Hendrickx, J., Woestenborghs, R., Heykants, J., 1994. Absorption, metabolism, and excretion of risperidone in humans. Drug Metab. Dispos., 21(6):1134-1141.

[10] McClean, S., O′Kane, E.J., Smyth, W.F., 2000. Electrospray ionisation-mass spectrometric characterisation of selected anti-psychotic drugs and their detection and determination in human hair samples by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B, 740(2):141-157.

[11] McCracken, J.T., McGough, J., Shah, B., Cronin, P., Hong, D., Aman, M.G., Davies, M., Arnold, L.M., Posey, D.J., Martin, A., et al., 2002. Risperidone in children with autism and serious behavioral problems. N. Engl. J. Med., 347(5):314-321.

[12] McDougle, C.J., Scahill, L., Aman, M.G., McCracken, J.T., Tierney, E., Arnold, L.M., Lindsay, R., 2005. Risperidone for the core symptom domains of autism: Results from the study by the autism network of the research units on pediatric psychopharmacology. Am. J. Psychiatry, 162(6):1142-1148.

[13] Moody, D.E., Laycock, J.D., Huang, W., Foltz, R.L., 2004. A high-performance liquid chromatographic-atmospheric pressure chemical ionization-tandem mass spectrometric method for determination of risperidone and 9-hydro-xyrisperidone in human plasma. J. Anal. Toxicol., 28(6):494-497.

[14] Remmerie, B.M., Sips, L.L., de Vries, R., de Jong, J., Schothuis, A.M., Hooijschuur, E.W., 2003. Validated method for the determination of risperidone and 9-hydroxyrisperidone in human plasma by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B, 783(2):461-472.

[15] Zhou, Z., Li, X., Li, K., Xie, Z., Cheng, Z., Peng, W., Wang, F., Zhu, R., Li, H., Flarakos, J., Luo, W., 2004. Simultaneous determination of clozapine, olanzapine, risperidone and quetiapine in plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry. J. Chromatogr. B, 802(2):257-262.