Determination of risperidone and its major metabolite 9-hydroxyrisperidone in human plasma by reversed-phase liquid chromatography with ultraviolet detection

Avenoso, Angela; Facciolà, Gabriella; Salemi, Monica; Spina, Edoardo

doi:10.1016/s0378-4347(00)00323-6

Cited by 88 publications

(60 citation statements)

References 16 publications

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“…Steady-state plasma concentrations of risperidone and 9-OHrisperidone were measured by HPLC according to the method of Avenoso et al [22]. The limit of quantification of the assay was 2 ng/mL for both analytes.…”

Section: Drug Assaysmentioning

confidence: 99%

Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia

D'Arrigo

Migliardi

Santoro

et al. 2005

Pharmacological Research

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The effect of fluvoxamine on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was investigated in 11 schizophrenic patients with prevailingly negative or depressive symptoms. Additional fluvoxamine, at the dose of 100 mg/day, was administered for 4 weeks to patients stabilized on risperidone (3-6 mg/day). Mean plasma concentrations of risperidone, 9-OH-risperidone and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) were not significantly modified following co-administration with fluvoxamine. After 4 weeks, fluvoxamine dosage was increased to 200 mg/day in five patients and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the six patients who were still receiving the initial fluvoxamine dose, while concentrations increased slightly but significantly (by a mean 26% over pretreatment; P < 0.05) in the subgroup of five subjects treated with a final dose of 200 mg/day. Fluvoxamine co-administration with risperidone was well tolerated and no patient developed extrapyramidal side effects. These findings indicate that fluvoxamine at dosages up to 100 mg/day is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of fluvoxamine may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of fluvoxamine on CYP2D6-and/or CYP3A4-mediated 9-hydroxylation of risperidone.

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Section: Drug Assaysmentioning

confidence: 99%

Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia

D'Arrigo

Migliardi

Santoro

et al. 2005

Pharmacological Research

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“…A RSP é biotransformada principalmente no fígado, através das isoenzimas do citocromo P450, principalmente por 9-hidroxilação e secundariamente por N-dealquilação e 7-hidroxilação (Avenoso et al, 2000;Spina et al, 2001). O principal metabólito circulante da RSP é a 9OH-RSP (Figura 4B), formada predominantemente através da reação de catalisação pela enzima CYP2D6 (Aravagiri e Marder, 2000;Avenoso et al, 2000;Llerena et al, 2003). A principal rota de eliminação da RSP é a renal (Cánovas et al, 2009).…”

Section: Farmacocinéticaunclassified

“…Alguns fatores podem influenciar nos níveis séricos da fração ativa, tais como: idade, lesões hepáticas e renais, genótipo da CYP2D6 e administração concomitante de outros medicamentos (Avenoso et al, 2000). No entanto, segundo Mauri et al (2001) a concentração da fração ativa não difere muito entre os indivíduos classificados como metabolizadores rápidos e lentos, isto porque nos metabolizadores rápidos, forma-se uma quantidade maior de 9OH-RSP e menor de RSP inalterada, sendo o inverso verificado nos metabolizadores lentos.…”

Section: Farmacocinéticaunclassified

“…As técnicas analíticas utilizadas para o controle de qualidade, determinação e quantificação da RSP são: espectrofotometria no ultravioleta, eletroforese capilar, cromatografia líquida de alta eficiência acoplada à espectrometria de massas (LC-MS), sendo a última a mais empregada nestes tipos de análises (Woestenborghs et al,1992 ;Olesen e Linnet, 1997 ;Balant-Gorgia et al, 1999 ;Nagasaki et al, 1999 ;Avenoso et al, 2000;Titier et al 2002 ;Llerena et al, 2003;Titier et al, 2003;Eerdekens et al, 2004Riedel et al, 2005Bharathi et al, 2007 ;Zhang et al, 2007b).…”

Section: Aspectos Analíticosunclassified

“…Diversas marcas de colunas cromatográficas têm sido descritas na literatura para este tipo de análise (Olesen e Linnet, 1997;Avenoso et al, 2000;Titier et al, 2002;Llerena et al, 2003;Riedel et al, 2005;Sattanathan et al, 2006;Zhang et al, 2007a;Zhang et al, 2007b;Bharathi et al, 2008), mas a maioria dos autores utilizou colunas cromatográficas C18 ou C8 e, por isso, priorizou-se a realização de testes com estes modelos de colunas.…”

Section: Avaliação Da Bioequivalência Entre Os Medicamentos Referênciunclassified

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Comparação da bioequivalência de duas formulações da risperidona

Belotto¹

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LISTA DE ABREVIATURAS 1,5; 3; 5; 8; 12; 24; 48; 72; 96 e 120 horas após a administração da medicação. A determinação da bioequivalência entre os dois medicamentos deu-se através da comparação dos parâmetros farmacocinéticos: concentração plasmática máxima (C max ), tempo para atingir a concentração plasmática máxima (T max ) e área sobre a curva de decaimento plasmático (ASC T ). Os resultados obtidos foram submetidos à análise de variância (ANOVA) e foi adotado o intervalo de confiança de 90% (IC 90%). Os valores médios para C max , T max e ASC T para RSP para os medicamentos referência e teste foram 16,02 ng/mL; 1,5 h e 348,94 ng.h/mL e 12,65 ng/mL; 1,5 h e 286,03 ng.h/mL, respectivamente. Já os valores médios para C max , T max e ASC T para 9OH-RSP para os medicamentos referência e teste foram 21,00 ng/mL; 5,0 h e 821,40 ng.h/mL e 17,85 ng/mL; 5,0 h e 632,92 ng.h/mL. Os valores de IC 90% para C max e ASC T para RSP para os medicamentos referência e teste foram 74 a 82% e 76 a 85%, respectivamente, e os valores de IC 90% para os mesmos parâmetros para 9OH-RSP foram 83 a 87% e 75 a 78%, respectivamente. Os resultados demonstraram diferenças significativas entre os medicamentos testados, o que permite concluir que os mesmos não são bioequivalentes e, portanto, não podem ser intercambiáveis.Descritores: equivalência terapêutica, risperidona, cromatografia líquida de alta pressão, farmacocinética. Brazil has launched programmes of public policies aiming to improve essential medicines access for the population since 1964. It was created in 1999 the National Agency for Sanitary Vigilance, which introduced the generic medicines in the Brazilian market, which already had the reference and the pharmaceutical equivalent ones. The objective of this study was to evaluate the bioequivalence and interchangeability between two antipsychotics (reference and pharmaceutical equivalent) used by the Institute of Psychiatry, Hospital of the Universidade de São Paulo, containing 2 mg of risperidone. It was developed and validated a high-performance liquid chromatography coupled to mass spectrometry method for the determination in plasma of risperidone (RSP) and its main metabolite, 9-hydroxy-risperidone (9OH-RSP). To assess bioequivalence between the medicines it was recruited 22 healthy volunteers, which took part in a clinical cross and random studies. The blood collections were performed on heparinizades tubes (5 ml) and runtimes collections were 0 (before medication); 0.25; 0.5; 1; 1.5; 3; 5; 8; 12; 24; 48; 72; 96 and 120 hours after the administration of medication. The determination of bioequivalence between the two drugs was achieved by a comparison of the following pharmacokinetic parameters: plasma concentration (C max ), time to achieve C max (T max ), and area under the plasma concentration-time curve (AUC T ).Results were subjected to analysis of variance (ANOVA), adopting a confidence interval CI 90%. The average values for Cmax, Tmax and AUCT for RSP were 16.02 ng/ml, 1.5 h and 348.94 ng.h/ml for reference medicines a...

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Determination of risperidone and 9‐Hydroxyrisperidone using HPLC, in plasma of children and adolescents with emotional and behavioural disorders

Jones

Breda

Charles

et al. 2009

Biomedical Chromatography

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A simple, rapid, selective, accurate and precise method is described for the determination of risperidone and its active metabolite, 9-hydroxyrisperidone, in plasma using a chemical derivative of risperidone (methyl-risperidone) as the internal standard. The sample workup involved a single-step extraction of 1 mL plasma, buffered to pH 10, with heptane-isoamyl alcohol (98:2 v/v), then evaporation of the heptane phase and reconstitution of the residue in mobile phase. HPLC separation was carried out at on C(18) column using a mobile phase of 0.05 m dipotassium hydrogen orthophosphate (containing 0.3% v/v triethylamine) adjusted to pH 3.7 with orthophosphoric acid (700 mL), and acetonitrile (300 mL). Flow rate was 0.6 mL/min and the detection wavelength was 280 nm. Retention times were 2.6, 3.7 and 5.8 min for 9-hydroxy risperidone, risperidone and the internal standard, respectively. Linearity in spiked plasma was demonstrated from 2 to 100 ng/mL for both risperidone and 9-hydroxyrisperidone (r > or = 0.999). Total imprecision was less than 13% (determined as co-efficient of variation) and the inaccuracy was less than 12% at spiked concentrations of 5 and 80 ng/mL. The limit of detection, determined as three times the baseline noise, was 1.5 ng/mL. Clinical application of the assay was demonstrated for analysis of post-dose (0.55-4.0 mg/day) samples from 28 paediatric patients (aged 6.9-17.9 years) who were taking risperidone orally for behavioural and emotional disorders.

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Determination of risperidone and its major metabolite 9-hydroxyrisperidone in human plasma by reversed-phase liquid chromatography with ultraviolet detection

Cited by 88 publications

References 16 publications

Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia

Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia

Comparação da bioequivalência de duas formulações da risperidona

Determination of risperidone and 9‐Hydroxyrisperidone using HPLC, in plasma of children and adolescents with emotional and behavioural disorders

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