Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, UT, United States; Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States.
Center for Human Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States.
J Pharm Biomed Anal. 2019 Apr 15;167:7-14. doi: 10.1016/j.jpba.2019.01.048. Epub 2019 Jan 29.
Budesonide is a potential therapeutic option for the prevention of bronchopulmonary dysplasia in mechanically ventilated premature neonates. The dose and concentrations of budesonide that drive effective prophylaxis are unknown, due in part to the difficulty in obtaining serial blood samples from this fragile population. Of primary concern is the limited total blood volume available for collection for the purposes of a pharmacokinetic study. Dried blood spots (DBS), which require the collection of <200 μL whole blood to fill an entire card, are an attractive low-blood volume alternative to traditional venipuncture sampling. We describe a simple and sensitive method for determining budesonide concentrations in DBS using an ultra-high-performance liquid chromatography - tandem mass spectrometry assay. Budesonide was liberated from a single 6 mm punch using a basified methyl tert-butyl ether extraction procedure. The assay was determined to be accurate and precise in the dynamic range of 1 to 50 ng/mL. The validated assay was then successfully applied to DBS collected as part of a multi-center, dose-escalation study of budesonide administered in surfactant via intra-tracheal instillation to premature neonates between 23 and 28 weeks gestational age. These findings show that DBS are a useful technique for collecting pharmacokinetic samples in premature neonates and other pediatric populations.
布地奈德是机械通气早产儿预防支气管肺发育不良的一种潜在治疗选择。由于从这个脆弱的人群中获得连续的血样存在困难，因此，驱动有效预防的布地奈德剂量和浓度尚不清楚。主要关注的问题是，为药代动力学研究收集的总血容量有限。干血斑（DBS），需要采集<200μL 的全血才能填满整个卡片，是一种有吸引力的低血量替代传统静脉穿刺采样的方法。我们描述了一种使用超高效液相色谱-串联质谱分析测定 DBS 中布地奈德浓度的简单灵敏方法。使用碱性甲基叔丁基醚提取程序从单个 6mm 冲头中释放布地奈德。该测定法在 1 至 50ng/mL 的动态范围内具有准确性和精密度。然后，该验证后的测定法成功地应用于 DBS 的采集，这些 DBS 是通过气管内滴注表面活性剂给予布地奈德的多中心剂量递增研究的一部分，纳入了 23 至 28 周胎龄的早产儿。这些发现表明，DBS 是在早产儿和其他儿科人群中采集药代动力学样本的有用技术。
