A low blood volume LC-MS/MS assay for the quantification of fentanyl and its major metabolites norfentanyl and despropionyl fentanyl in children.
A low blood volume LC-MS/MS assay for the quantification of fentanyl and its major metabolites norfentanyl and despropionyl fentanyl in children.
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DOI：
10.1002/jssc.201100422
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发表时间：
2011-12
影响因子：
3.1
通讯作者：
C. Clavijo;J. Thomas;M. Cromie;B. Schniedewind;K. Hoffman;U. Christians;J. Galinkin
中科院分区：
文献类型：
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作者：
C. Clavijo;J. Thomas;M. Cromie;B. Schniedewind;K. Hoffman;U. Christians;J. Galinkin
早产儿和足月新生儿通常需要手术和镇痛。然而，我们的知识芬太尼，最常用的药物，这些程序，其代谢产物的新生儿药代动力学仍然是不完整的。为了便于芬太尼及其代谢产物在新生儿和其他儿童中的药代动力学研究，我们开发并验证了基于微创，低血容量采样的LC-MS/MS方法。LC-MS/MS用于从滤纸上收集的干燥血液样品（DBS）中同时分析芬太尼、去丙酰芬太尼（DPF）和去甲芬太尼。使用多反应监测来监测正离子。由于用于测量芬太尼血液浓度的标准基质是血浆，因此在血浆、全血和DBS中开发并验证了该测定法。我们的方法能够测量芬太尼及其代谢物的临床相关水平。在DBS中，芬太尼的定量下限为100 pg/mL，可靠响应范围为0.1至100 ng/mL（r（2）>0.99），DPF和去甲芬太尼的定量下限均为250 pg/mL，可靠响应范围为0.25至100 ng/mL（r（2）>0.99）。血浆和DBS中芬太尼的日间准确度和精密度符合预定义的验收标准，也表明两种基质中的测定性能相当。
Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most commonly used drug for these procedures, and its metabolites is still incomplete. To facilitate pharmacokinetic studies of fentanyl and its metabolites in neonates and other children, we developed and validated an LC-MS/MS method based on minimally invasive, low blood volume sampling. LC-MS/MS was used for the simultaneous analysis of fentanyl, despropionyl fentanyl (DPF), and norfentanyl from dried blood samples (DBS) collected on filter paper. Positive ions were monitored using multiple reaction monitoring. Since the standard matrix for measuring fentanyl blood concentrations is plasma, the assay was developed and validated in plasma, whole blood, and then DBS. Our method was able to measure clinically relevant levels of fentanyl and its metabolites. In DBS, the lower limits of quantification were 100 pg/mL for fentanyl with a range of reliable response from 0.1 to 100 ng/mL (r(2)>0.99) and 250 pg/mL for both DPF and norfentanyl with a range of reliable response from 0.25 to 100 ng/mL (r(2)>0.99). In plasma and in DBS inter-day accuracy and precisions of fentanyl met predefined acceptance criteria and also indicated comparable assay performance in both matrices.