Clinica chimica acta; international journal of clinical chemistry · 2025
Incorporating measurement uncertainty into free valproic acid monitoring: estimation and clinical impact for therapeutic drug monitoring.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Rigo-Bonnin Raúl, Mas-Bosch Virgínia, Blanco-Font Aurora
Аннотация
BACKGROUND: Valproic acid (VPA) is widely prescribed for epilepsy and other neurological conditions. Its clinical management is challenging due to nonlinear pharmacokinetics, extensive protein binding, and a narrow therapeutic interval. Since only the unbound ("free") fraction is pharmacologically active, monitoring the concentrations of free VPA in serum is more informative than total levels. Both direct measurement and predictive equations are subject to measurement uncertainty (MU), which may influence therapeutic interpretation.
OBJECTIVES: To estimate MU for free VPA concentrations using both direct measurement and published predictive equations, and to assess how MU-aware reporting affects therapeutic classification relative to the (5-15) mg/L therapeutic interval.
MATERIAL AND METHODS: Free and total VPA concentrations were determined by equilibrium dialysis coupled with LC-MS/MS and compared with ten published predictive equations. MU was estimated following ISO/TS 20914:2019 and the GUM, in line with ISO 15189:2022. Uncertainty budgets were constructed, and nine patient cases were analyzed, comparing therapeutic classification with and without MU consideration.
RESULTS: Direct measurement showed a relative MU ranging from 5 % to 8 %. Predictive equations displayed broader and more variable uncertainty, particularly in hypoalbuminemic and ICU patients. Incorporating MU altered therapeutic classification in 4 of 9 patients (44 %), mainly near the lower decision limit (5 mg/L), leading to more results reported as "indeterminate."
CONCLUSIONS: Reporting free VPA concentrations with MU may reduce the risk of misclassification and enhance transparency, aligning with ISO 15189:2022 accreditation requirements. Explicit consideration of MU in therapeutic drug monitoring represents a step toward safer, evidence-based clinical practice.
OBJECTIVES: To estimate MU for free VPA concentrations using both direct measurement and published predictive equations, and to assess how MU-aware reporting affects therapeutic classification relative to the (5-15) mg/L therapeutic interval.
MATERIAL AND METHODS: Free and total VPA concentrations were determined by equilibrium dialysis coupled with LC-MS/MS and compared with ten published predictive equations. MU was estimated following ISO/TS 20914:2019 and the GUM, in line with ISO 15189:2022. Uncertainty budgets were constructed, and nine patient cases were analyzed, comparing therapeutic classification with and without MU consideration.
RESULTS: Direct measurement showed a relative MU ranging from 5 % to 8 %. Predictive equations displayed broader and more variable uncertainty, particularly in hypoalbuminemic and ICU patients. Incorporating MU altered therapeutic classification in 4 of 9 patients (44 %), mainly near the lower decision limit (5 mg/L), leading to more results reported as "indeterminate."
CONCLUSIONS: Reporting free VPA concentrations with MU may reduce the risk of misclassification and enhance transparency, aligning with ISO 15189:2022 accreditation requirements. Explicit consideration of MU in therapeutic drug monitoring represents a step toward safer, evidence-based clinical practice.