Bachmann Fabio, Blaser Lea, Haschke Manuel, Krähenbühl Stephan, Duthaler Urs
Department of Biomedicine, Division of Clinical Pharmacology & Toxicology, University & University Hospital Basel, 4031 Basel, Switzerland.
Department of General Internal Medicine, Clinical Pharmacology & Toxicology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
Bioanalysis. 2020 Feb;12(3):175-189. doi: 10.4155/bio-2019-0251. Epub 2020 Feb 13.
Metamizole is a frequently used antipyretic and analgesic prodrug, yet its pharmacokinetics has not been thoroughly studied in infants and with coadministered medications. Thus, an LC-MS/MS method was developed to quantify the four major metamizole metabolites in human plasma. Pre- and postcolumn infusion was installed to enable robust analyte retention and electrospray ionization following deproteinization of plasma samples. The method was linear (R > 0.996), accurate (93.1-106.0%) and precise (≤12.7%). Mean recovery was more than 91.8% and ion suppression less than 13.1% for all analytes. Pharmacokinetic profiles were reproducible after 4 years at -80°C except for the formylated metabolite (-22.2%). The method fulfilled pertinent criteria of validation guidelines and required only little sample volume. The method therefore qualifies for metamizole analyses in children.
安乃近是一种常用的解热镇痛前体药物，但其在婴儿体内以及与其他药物合用时的药代动力学尚未得到充分研究。因此，开发了一种液相色谱-串联质谱法来定量测定人血浆中的四种主要安乃近代谢物。安装了柱前和柱后注入装置，以便在血浆样品脱蛋白后实现稳定的分析物保留和电喷雾电离。该方法线性良好（R>0.996）、准确（93.1-106.0%）且精密度高（≤12.7%）。所有分析物的平均回收率均超过91.8%，离子抑制率小于13.1%。除甲酰化代谢物外（-22.2%），药代动力学特征在-80°C保存4年后仍具有可重复性。该方法符合验证指南的相关标准，且仅需少量样本量。因此，该方法适用于儿童安乃近分析。
