Abstract：
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs that can cause liver toxicity. The aim of this study was to integrate bioanalytical and population pharmacokinetic (PopPK) assay to rapidly screen and quantify the concentrations of NSAIDs in plasma and monitor clinical safety. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetaminophen (APAP), flurbiprofen (FLB), aspirin (ASP), and ibuprofen (IBP), four commonly used NSAIDs. The PopPK model of the signature toxicant was analyzed based on the published literature. The LC-MS/MS method was successfully validated and applied to determine NSAID concentrations in patient plasma samples. APAP, ASP, and IBP data were best fitted using a one-compartment model, and FLB data were best fitted using a two-compartment model. Bootstrapping and visual predictive checks suggested that a robust and reliable pharmacokinetic model was developed. A fast, simple, and sensitive LC-MS/MS method was developed and validated for determining APAP, FLB, ASP, and IBP in human plasma. Combined with the PopPK model, this method was applied to rapidly analyze the concentrations of NSAIDs in clinical samples from patients presenting to the emergency department with acute liver dysfunction and monitored NSAIDs clinical safety.
摘要：
非甾体抗炎药（NSAIDs）是最常用的可引起肝毒性的药物之一。这项研究的目的是整合生物分析和群体药代动力学（PopPK）测定，以快速筛选和定量血浆中NSAID的浓度并监测临床安全性。建立了同时定量对乙酰氨基酚（APAP）的液相色谱-串联质谱（LC-MS/MS）方法，氟比洛芬（FLB），阿司匹林（ASP），布洛芬（IBP），四种常用的NSAIDs。根据已发表的文献分析了特征毒物的PopPK模型。LC-MS/MS方法已成功验证并用于确定患者血浆样品中的NSAID浓度。APAP,ASP,和IBP数据最好使用单室模型拟合，和FLB数据最好使用两室模型拟合。自举和视觉预测检查表明，开发了一个稳健可靠的药代动力学模型。一个快速的，简单,和灵敏的LC-MS/MS方法开发和验证测定APAP，FLB,ASP,和人血浆中的IBP。结合PopPK模型，该方法用于快速分析急诊急性肝功能不全患者临床样本中NSAIDs的浓度,并监测NSAIDs临床安全性.
