Head-to-Head Comparison of UHPLC-MS/MS and Alinity C for Plasma Analysis of Risperidone and Paliperidone

<b>Background and objectives:</b> Risperidone, a second-generation antipsychotic widely used in the treatment of schizophrenia, requires therapeutic drug monitoring due to its high interindividual variability. UHPLC-MS/MS is considered the gold standard for pharmacokinetic studies owing...

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Main Authors: Francisco José Toja-Camba, Gonzalo Hermelo-Vidal, Carolina Feitosa-Medeiros, María Vidal-Millares, María José Durán-Maseda, Anxo Fernández-Ferreiro, Cristina Mondelo-García
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/17/11/1446
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Summary:<b>Background and objectives:</b> Risperidone, a second-generation antipsychotic widely used in the treatment of schizophrenia, requires therapeutic drug monitoring due to its high interindividual variability. UHPLC-MS/MS is considered the gold standard for pharmacokinetic studies owing to its superior sensitivity and specificity, although it involves time-consuming manual sample preparation. In contrast, the Alinity C system, fully automated, simplifies sample processing, but only measures the active moiety (risperidone plus paliperidone). The aim of this study is to compare the performance of UHPLC-MS/MS and the Alinity C system for the determination of risperidone and paliperidone concentrations in plasma. <b>Methods:</b> A total of 115 plasma samples of 115 patients, 92 and 23 under risperidone and paliperidone long-acting treatment, respectively, were analyzed using both methods. <b>Results:</b> A strong correlation for the active moiety (risperidone plus 9-OH-Risperidone) (rs = 0.95) was observed. However, Bland–Altman analysis revealed a mean bias of 0.996 ng/mL, indicating that the Alinity C system slightly overestimates concentrations compared to UHPLC-MS/MS. While there was substantial agreement between methods (κ = 0.72), discrepancies were observed in 16.3% of cases, which could impact clinical decision-making. When analyzing paliperidone separately, the agreement was lower (κ = 0.63), with greater variability observed. <b>Conclusions:</b> These findings suggest that, while the Alinity C system is suitable for routine therapeutic monitoring, UHPLC-MS/MS remains the preferred method in clinical scenarios requiring higher precision, particularly for patients with concentrations near therapeutic thresholds.
ISSN:1424-8247