Validated method for the determination of risperidone and 9-hydroxyrisperidone in human plasma by liquid chromatography–tandem mass spectrometry

Remmerie, Bart; Sips, Luc; Vries, Ronald de; Jong, Jan de; Schothuis, A.M; Hooijschuur, Edwin W. J.; Merbel, Nico C. van de

doi:10.1016/s1570-0232(02)00715-8

Cited by 80 publications

(76 citation statements)

References 12 publications

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“…To check whether the dose of paliperidone used in the 21-day chronic study is within the clinical range, plasma aliquots extracted at the end of the last session of stress were purified using mixed mode cation exchange solid-phase extraction columns, and paliperidone levels were measured using a sensitive high-performance liquid chromatography with electrospray tandem mass spectrometer as described previously [27]. The paliperidone concentration found was under the detection limit in control animals (<1.5 ng/mL).…”

Section: Drug Administration and Experimental Designmentioning

confidence: 99%

The Atypical Antipsychotic Paliperidone Regulates Endogenous Antioxidant/Anti-Inflammatory Pathways in Rat Models of Acute and Chronic Restraint Stress

et al. 2016

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Alterations in the innate inflammatory response may underlie the pathophysiology of psychiatric diseases. Current antipsychotics modulate pro-/anti-inflammatory pathways, but their specific actions on these pathways remain only partly explored. This study was conducted to elucidate the regulatory role of paliperidone (1 mg/kg i.p.) on acute (6 h) and chronic (6 h/day for 21 consecutive days) restraint stressinduced alterations in 2 emerging endogenous anti-inflammatory/antioxidant mechanisms: nuclear factor erythroid-related factor 2 (NRF2)/antioxidant enzymes pathway, and the cytokine milieu regulating M1/M2 polarization in microglia, analyzed at the mRNA and protein levels in prefrontal cortex samples. In acute stress conditions, paliperidone enhanced NRF2 levels, possibly related to phosphoinositide 3-kinase upregulation and reduced kelch-Like ECH-associated protein 1 expression. In chronic conditions, paliperidone tended to normalize NRF2 levels through a phosphoinositide 3-kinase related-mechanism, with no effects on kelch-Like ECH-associated protein 1. Antioxidant response element-dependent antioxidant enzymes were upregulated by paliperidone in acute stress, while in chronic stress, paliperidone tended to prevent stress-induced downregulation of the endogenous antioxidant machinery. However, paliperidone increased transforming growth factor-β and interleukin-10 in favor of an M2 microglia profile in acute stress conditions, which was also corroborated by paliperidone-induced increased levels of the M2 cellular markers arginase I and folate receptor 2. This latter effect was also produced in chronic conditions. Immunofluorescence studies suggested an increase in the number of microglial cells expressing arginase I and folate receptor 2 in the stressed animals pretreated with paliperidone. In conclusion, the enhancement of endogenous antioxidant/anti-inflammatory pathways by current and new antipsychotics could represent an interesting therapeutic strategy for the future.

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Section: Drug Administration and Experimental Designmentioning

confidence: 99%

The Atypical Antipsychotic Paliperidone Regulates Endogenous Antioxidant/Anti-Inflammatory Pathways in Rat Models of Acute and Chronic Restraint Stress

et al. 2016

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“…Although these methods may be suited for therapeutic drug monitoring of target concentrations in the range of 4 -30 ng/ml for risperidone and 15 -60 ng/ml for the sum of parent drug and 9-hydroxymetabolites ('active moiety'), their lower levels of quantification (0.5 ng/ml and 5 ng/ml, respectively) are not particularly suited for pharmacokinetic studies. In recent years several mass spectrometric methods have been developed that all have much improved sensitivity and specificity [10][11][12][13][14][15]. Recently it was found that the metabolism of RIS results in the formation of two enantiomers, (+)9-hydroxyrisperidone and (-)9-hydroxyrisperidone, and that the enantioselective hydroxylation is catalyzed by CYP2D6 and CYP3A4, with the CYP3A4 pathway metabolizing at a slower formation rate [16].…”

Section: Introductionmentioning

confidence: 99%

Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS

Cabovska

Cox

Vinks

2007

Journal of Chromatography B

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A robust and validated liquid-liquid extraction LC-MS/MS method was developed for population pharmacokinetic analysis and therapeutic drug monitoring of risperidone and the enantiomers of its major active metabolite (+)-and (-)9-hydroxyrisperidone in pediatric patients. The method was rapid, sensitive and used a low sample amount (200 μL), which is very desirable for the pediatric population. The assay was validated from 0.2 -50 ng/mL in plasma for all analytes. LLOQ for all analytes was 0.2 ng/mL. The extracts were analyzed by normal phase LC-MS/MS. The sample run time was 8 minutes. Intra-and interday precision for all analytes was ≤ 6 %; method accuracy was between 89 and 99 %. Additional experiments were performed to analyze matrix effects and identify a proper internal standard for each analyte. The validated method was used to study risperidone and its enantiomer metabolites in plasma as part of a population pharmacokinetic study in pediatric patients with pervasive developmental disorder (PDD).

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“…These are very effective and offer high recoveries (> 85 %) with good precision and accuracy, but sample handling requires the use of toxic solvents or multiple extraction steps in order to obtain clean extracts, and this factor is a drawback when the analysis demands to work with a large sample number. On the other hand, solid phase extraction (SPE) procedures offer an easier sample handling but the results are reliable only if the analyst avoids sorbent drying 7,10,[12][13][14][15] . In our laboratory, we tested the properties of the sorbent included in Waters OASIS ® HLB cartridges because it offer more advantages compared to traditional SPE 16 .…”

Section: E-mail: Cvonples@udeccl; Corresponding Authormentioning

confidence: 99%

“…Furthermore, the time required to perform extraction of RSP and 9-OH with the OASIS HLB sorbent can be reduced using 96-well plates and automatic sample processing systems (less time and solvent consumption), or with the use of more sensitive detection modes, such as mass spectrometry, which requires less sample for analysis, smaller injection volumes and provides higher sensitivity than UV detection [8][9][10][11] .…”

Section: -Conclusionmentioning

confidence: 99%

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Pharmacokinetic Study of Risperidone: Application of a HPLC Method With Solid Phase Extraction

TORRES¹,

C²,

R³

2011

J. Chil. Chem. Soc.

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A new, simplified solid phase extraction procedure for the determination of risperidone and 9-hydroxyrisperidone in human plasma has been developed. This method involves the use of an optimized extraction protocol developed in Waters OASIS ® HLB 30mg 1cc extraction columns using 1 mL of human serum. Separation was performed by HPLC using a Waters XTerra RP-18 (5 µm, 150x4,6 mm) column with a mobile phase consisting in acetonitrile -potassium dihydrogen phosphate 50 mM pH 3.4 (27/73). UV detection at 278 nm was used to quantify analytes, encountering good linearity (r 2 > 0.999) in the 2-100 ng/mL concentration range. The mean recovery was 92.4 % and 92.8 % for risperidone and 9-hydroxyrisperidone respectively, with an intraday -interday precision below 7%, and accuracy below 115 %. The method has been successfully applied in pharmacokinetic studies that require a large sample number.Keywords: Risperidone, 9-hydroxyrisperidone, solid phase extraction. 1.-INTRODUCTIONRisperidone (RSP, figure 1) is a benzoisoxazole derivative that is clinically used as an atypical antipsychotic. Since its introduction in the 1990s, it has been considered to be a first-rate choice in the treatment of schizophrenia and other mental disorders because of its pharmacodynamics 1 (selective blocking of 5-HT2 and D2 receptors in brain), providing effective management of positive, negative and cognitive symptoms of schizophrenia with a low profile of extrapyramidal and autonomic side effects 2 .Several methods have been proposed for therapeutic and toxicological monitoring of RSP and 9-hydroxyrisperidone (9-OH RSP, figure 1). These are more-or-less sensitive depending on the detection mode used. UV detection offers simplicity but higher limit of quantitation (LOQ=2 ng/ml) and presence of interferents if the extraction procedure is not selective 3.4.5 . Electrochemical detection offers lower LOQ (< 0.5 ng/mL) but lacks selectivity and sample and standard preparation require high purity reagents 6,7 . Ultimately, mass spectrometry detection offers high sensitivity and selectivity, but the cost is not accessible for most laboratories, especially in Latin America 8-11 . e-mail: cvonples@udec.cl; corresponding authorFigure 1: Chemical structures of Risperidone, 9-OH hydroxyrisperidone and Clozapine.The extraction procedures described to isolate RSP and 9-OH RSP from biological matrices are predominantly based on liquid-liquid extraction [3][4][5]8,9,11 . These are very effective and offer high recoveries (> 85 %) with good precision and accuracy, but sample handling requires the use of toxic solvents or multiple extraction steps in order to obtain clean extracts, and this factor is a drawback when the analysis demands to work with a large sample number. On the other hand, solid phase extraction (SPE) procedures offer an easier sample handling but the results are reliable only if the analyst avoids sorbent drying 7,10,[12][13][14][15] . In our laboratory, we tested the properties of the sorbent included in Waters OASIS ® HLB cartridges be...

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Validated method for the determination of risperidone and 9-hydroxyrisperidone in human plasma by liquid chromatography–tandem mass spectrometry

Cited by 80 publications

References 12 publications

The Atypical Antipsychotic Paliperidone Regulates Endogenous Antioxidant/Anti-Inflammatory Pathways in Rat Models of Acute and Chronic Restraint Stress

The Atypical Antipsychotic Paliperidone Regulates Endogenous Antioxidant/Anti-Inflammatory Pathways in Rat Models of Acute and Chronic Restraint Stress

Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS

Pharmacokinetic Study of Risperidone: Application of a HPLC Method With Solid Phase Extraction

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