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Online extraction of antihypertensive drugs and their metabolites from untreated human serum samples using restricted access carbon nanotubes in a column switching liquid chromatography system
Journal of Chromatography A ( IF 3.8 ) Pub Date : 2017-10-31 , DOI: 10.1016/j.chroma.2017.10.072
Henrique Dipe de Faria , Carolina Tosin Bueno , Jose Eduardo Krieger , Eduardo Moacyr Krieger , Alexandre Costa Pereira , Paulo Caleb Júnior Lima Santos , Eduardo Costa Figueiredo

A novel analytical method was developed to determine 5 antihypertensive drugs of different pharmacological classes (angiotensin-converting enzyme inhibitors, calcium channel blockers, α-2 adrenergic receptor agonists, angiotensin II receptor blockers, and aldosterone receptor antagonists) and some of their metabolites in human serum. The untreated samples were directly analyzed in a column switching system using an extraction column packed with restricted access carbon nanotubes (RACNTs) in an ultra-high performance liquid chromatography coupled to a mass spectrometer (UHPLC–MS/MS). The RACNTs column was able to exclude approximately 100% of proteins from the samples in 2.0 min, maintaining the same performance for about 300 analytical cycles. The method was validated in accordance with Food and Drug Administration (FDA) guidelines, being linear for all the determined analytes in their respective analytical ranges (coefficients of determination higher than 0.99) with limits of detection (LODs) and quantification (LOQs) ranging from 0.09 to 10.85 μg L−1 and from 0.30 to 36.17 μg L−1, respectively. High recovery values (88–112%) were obtained as well as suitable results for inter and intra-assay accuracy and precision. The method provided an analytical frequency of 5 samples per hour, including the sample preparation and separation/detection steps. The validated method was successfully used to analyze human serum samples of patients undergoing treatment with antihypertensive drugs, being useful for pharmacometabolomic, pharmacogenomic, and pharmacokinetic studies.



中文翻译:

在柱切换液相色谱系统中使用限制进入的碳纳米管从未经处理的人血清样品中在线提取降压药及其代谢物

开发了一种新的分析方法来确定5种不同药理学类别的降压药(血管紧张素转换酶抑制剂,钙通道阻滞剂,α-2肾上腺素能受体激动剂,血管紧张素II受体阻滞剂和醛固酮受体拮抗剂)及其在人体中的某些代谢物血清。未经处理的样品在装有填料的限制进出碳纳米管(RACNT)的萃取柱中,在与质谱仪(UHPLC-MS / MS)联用的超高效液相色谱仪中,直接在柱切换系统中进行分析。RACNTs色谱柱能够在2.0分钟内从样品中排除大约100%的蛋白质,从而在大约300个分析循环中保持相同的性能。该方法已根据美国食品药品监督管理局(FDA)的准则进行了验证,-1和0.30至36.17μgL -1。获得了较高的回收率(88–112%),并获得了批内和批内准确性和精密度的合适结果。该方法提供了每小时5个样品的分析频率,包括样品制备和分离/检测步骤。经过验证的方法已成功用于分析接受降压药治疗的患者的人血清样品,可用于药代动力学,药物基因组学和药代动力学研究。

更新日期:2017-10-31
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