A Novel Application of the Volumetric Absorptive Micro Sampling Strategy to Quantify Dexmedetomidine in Capillary Blood Using an LC – MS / MS Method

BACKGROUND: Pain control in neonates is crucial as inadequate management may impair neuronal development. Dexmedetomidine (DEX), an alpha2 agonist, is approved for intravenous use in ventilated neonates. While intranasal DEX is off-label in neonates and children, studies show its efficacy for magnetic resonance imaging sedation. Limited pharmacokinetic data exist for intranasal DEX in pre-term infants and neonates. This study aimed to develop an analytical method for DEX quantification in blood samples (20 μL) of complex patients collected with microsampling technique to enable future pharmacokinetic studies. METHODS: A liquid-liquid extraction from blood absorbed in microsampling devices (MITRA) and an LC-MS/MS method were developed and validated following EMA/FDA guidelines. The method's suitability was verified by comparing results from nine paediatric blood samples collected in EDTA tubes or using MITRA devices. RESULTS: > 0.99), intra and inter-day repeatability (CV % 1.8-11.8), stability, and hematocrit effect met the acceptance criteria for bioanalytical method validation. Compared with plasma samples, the proposed method showed good consistency in detecting DEX in MITRA samples. CONCLUSION: The MITRA microsampling tools reduce the amount of blood needed and the risks of anemisation for neonates hospitalised and simplifies procedures, allowing a reduction of the staff involved in the routine. The analytical and clinical validation of the method demonstrated its suitability to quantify DEX in a range of concentrations potentially useful for pharmacokinetic studies in paediatric patients for approval use and drug monitoring.