Determination of risperidone and 9-hydroxyrisperidone in human plasma by high-performance liquid chromatography: application to therapeutic drug monitoring in Japanese patients with schizophrenia.
ABSTRACT A high-performance liquid chromatographic method has been developed for the simultaneous determination of risperidone and its major active metabolite 9-hydroxyrisperidone in plasma. Risperidone and 9-hydroxyrisperidone in plasma were extracted using a CN bonded-solid phase cartridge, followed by, C4 reversed-phase HPLC separation. Risperidone, 9-hydroxyrisperidone and trazodone as an internal standard were detected by ultraviolet absorbance at 280 nm. It was possible to determine risperidone in the concentration range of 1.0-100.0 ng/ml(-1) and 9-hydroxyrisperidone at a range of 2.0-200.0 ng/ml(-1). The detection limits of risperidone and 9-hydroxyrisperidone were 0.5 and 1.0 ng/ml(-1), respectively. The mean recoveries of risperidone and 9-hydroxyrisperidone added to plasma were less than 92.0 and 92.6%, with a coefficient of variation of less than 10.6 and 10.5%, respectively. This method has been used for the simultaneous determination of steady-state plasma concentration (Css) of risperidone and 9-hydroxyrisperidone in schizophrenic patients treated with 3-, 6-, and 12-mg risperidone oral doses per day.
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ABSTRACT: Although risperidone is commonly used in the acute and maintenance treatment of schizophrenia, the role of therapeutic drug monitoring has yet to be elucidated. The purpose of this review was to determine whether risperidone warrants therapeutic drug monitoring in patients with schizophrenia. Using a previously published nine-step decision-making algorithm, the available evidence was examined to determine whether therapeutic drug monitoring of risperidone is warranted in adult schizophrenic patients. Analytical methods used to quantify risperidone, 9-hydroxyrisperidone, and the combined active moiety are specific, sensitive, accurate, and precise; however, the therapeutic range for risperidone has not yet been established. Relationships between risperidone dose and plasma concentrations of risperidone, 9-hydroxyrisperidone, or the active moiety have not yet been demonstrated. A clear correlation between plasma risperidone concentrations and therapeutic response has also not been shown. Intrinsic interpatient variability, genetically based differences in drug metabolism, and metabolic drug interactions may all influence the variability in plasma concentrations. Patients with schizophrenia on risperidone for prevention of relapse take the medication for a sufficient duration of therapy to benefit from therapeutic drug monitoring; however, the routine use of risperidone concentrations in all patients with schizophrenia is not likely to have a significant impact on the clinical decision-making process or provide more information than clinical judgment alone. The routine use of risperidone levels does not seem warranted in all patients with schizophrenia. Clinical end points (ie, response and toxicity) should be monitored by assessing changes in symptoms and emergence of adverse effects, especially extrapyramidal symptoms. Therapeutic drug monitoring of risperidone may be beneficial in certain circumstances, including assessing potential noncompliance and supporting compliance, ruling out therapeutic failure as a result of low drug concentrations, and identifying and managing drug interactions, adverse effects, and use in special populations.Therapeutic drug monitoring 03/2011; 33(3):275-83. · 2.43 Impact Factor
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ABSTRACT: A simple, linear gradient, rapid, precise and stability-indicating analytical method was developed for the estimation of related substances and degradants of paliperidone API and tablets. The chromatographic separations were achieved using an Acquity ultra-performance liquid chromatograph (BEH 100 mm, 2.1 mm, 1.7 µm C-18 column) employing 0.01 M potassium dihydrogen phosphate buffer (pH 2.0) as mobile phase A and acetonitrile-water (9:1) as mobile phase B. A linear gradient (mobile phase A, mobile phase B in the ratio of 84:16) with a 0.45 mL/min flow rate was chosen. All six impurities were eluted within five minutes of run time. The column temperature was maintained at 25 °C and a detector wavelength of 238 nm was employed. Paliperidone was exposed to thermal, photolytic, hydrolytic and oxidative stress conditions. The stressed samples were analyzed by the proposed method. Considerable degradation of the analyte was observed when it was subjected to oxidative conditions and impurity F was found to be the major degradant. Peak homogeneity data of paliperidone obtained by photodiode array (PDA) detection demonstrated the specificity of the method in the presence of degradants. The method was validated with respect to linearity, precision, accuracy, ruggedness, robustness, limit of detection and limit of quantification.Journal of chromatographic science 04/2012; 50(4):368-72. · 0.79 Impact Factor
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ABSTRACT: The aim of this review is to provide information for interpreting outcome results from monitoring of antipsychotics in biological samples. A brief overview of the working mechanisms, pharmacological effects, drug interactions, and analytical methods of classical and atypical antipsychotics is given. Nineteen antipsychotics were selected based on their importance in the worldwide market as follows: amisulpride, aripiprazole, asenapine, bromperidol, clozapine, flupenthixol, haloperidol, iloperidone, lurasidone, olanzapine, paliperidone, perphenazine, pimozide, pipamperone, quetiapine, risperidone, sertindole, sulpiride, and zuclopenthixol. A straightforward relationship between administered dose, plasma or serum concentration, clinical outcome, or adverse effects is often lacking. Nowadays, focus lies on therapeutic drug monitoring and individualized therapy to find adequate treatment, to explain treatment failure or nonresponse, and to check patient compliance. However, extensive research in this field is still mandatory.Therapeutic drug monitoring 12/2012; 34(6):629-651. · 2.43 Impact Factor