干血斑
色谱法
治疗药物监测
副黄嘌呤
茶碱
分析物
血液取样
串联质谱法
甲酸
化学
选择性反应监测
萃取(化学)
全血
药代动力学
质谱法
医学
药理学
外科
CYP1A2
生物化学
细胞色素P450
新陈代谢
内科学
作者
Hao-Ran Dai,Hongli Guo,Weijun Wang,Xian Shen,Rui Cheng,Jing Xu,Yahui Hu,Xiaowen Ding,Feng Chen
标识
DOI:10.1515/cclm-2023-0310
摘要
Abstract Objectives To update traditional “wet” matrices to dried blood spot (DBS) sampling, based on the liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) technique, and develop a method for simultaneous analyzing caffeine and its three primary metabolites (theobromine, paraxanthine, and theophylline), supporting routine therapeutic drug monitoring (TDM) for preterm infants. Methods DBS samples were prepared by a two-step quantitative sampling method, i.e., volumetric sampling of a quantitative 10 μL volume of peripheral blood and an 8 mm diameter whole punch extraction by a methanol/water (80/20, v/v) mixture containing 125 mM formic acid. Four paired stable isotope labeled internal standards and a collision energy defect strategy were applied for the method optimization. The method was fully validated following international guidelines and industrial recommendations on DBS analysis. Cross validation with previously developed plasma method was also proceeded. The validated method was then implemented on the TDM for preterm infants. Results The two-step quantitative sampling strategy and a high recovery extraction method were developed and optimized. The method validation results were all within the acceptable criteria. Satisfactory parallelism, concordance, and correlation were observed between DBS and plasma concentrations of the four analytes. The method was applied to provide routine TDM services to 20 preterm infants. Conclusions A versatile LC-MS/MS platform for simultaneous monitoring caffeine and its three primary metabolites was developed, fully validated, and successfully applied into the routine clinical TDM practices. Sampling method switching from “wet” matrices to “dry” DBS will facilitate and support the precision dosing of caffeine for preterm infants.
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