Determination of Ibuprofen Enantiomers in Mouse Blood Using Liquid Chromatography–Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study

IF 2.8 4区化学 Q2 CHEMISTRY, ANALYTICAL

Chirality Pub Date : 2024-10-08 DOI:10.1002/chir.23721

Yuexin Li, Jinglai Li, Huanhuan Yang, Huan Luo, Shiqi Liu, Furong Han, Zhipeng Ruan, Zhili Xiong

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Abstract

The aim of this study was to establish a simple, fast, and sensitive method with liquid chromatography–tandem mass spectrometry (LC–MS/MS) for simultaneously determining ibuprofen enantiomers using mouse blood in very small volumes. LC–MS/MS equipped with an electrospray ionization (ESI) source was used in negative ion mode and multiple-reaction monitoring mode. Enantiomer chromatographic separation was carried out on a Lux® 5 μm Cellulose-3 (250 × 4.6 mm, 5 μm) column at a flow rate of 0.6 mL/min. Samples were pretreated by extracting only 5 μL of blood with 40 μL of acetonitrile (containing 1.3% formic acid) so that a concentration-time profile could be completed using a single mouse. 2-(4-Propylphenyl) propanoic acid was used as an internal standard. Standard curves for each enantiomer were linear from 0.04 to 80.00 μg/mL, demonstrating a lower limit of quantitation (LLOQ) than all previously reported methods. This method was completely validated and successfully executed to investigate the pharmacokinetics of ibuprofen enantiomers after intravenous administration of racemic ibuprofen, (S)-(+)-ibuprofen, and (R)-(−)-ibuprofen in Kunming mice, respectively. The results showed that the pharmacokinetic profiles of the (R)-(−)-ibuprofen and (S)-(+)-ibuprofen were significantly different, indicating the unidirectional inversion of R-(−)-ibuprofen to (S)-(+)-ibuprofen.

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利用液相色谱-串联质谱法测定小鼠血液中的布洛芬对映体及其在药代动力学研究中的应用

本研究旨在利用液相色谱-串联质谱（LC-MS/MS）建立一种简单、快速、灵敏的方法，利用极少量的小鼠血液同时测定布洛芬对映体。LC-MS/MS 配有电喷雾离子源，采用负离子模式和多反应监测模式。对映体色谱分离采用 Lux® 5 μm Cellulose-3（250 × 4.6 mm，5 μm）色谱柱，流速为 0.6 mL/min。用 40 μL 乙腈（含 1.3% 甲酸）提取 5 μL 血液样品进行预处理，以便用一只小鼠完成浓度-时间曲线。2-(4-丙基苯基)丙酸用作内标。每种对映体的标准曲线在 0.04 至 80.00 μg/mL 之间呈线性关系，表明其定量限（LLOQ）低于之前报道的所有方法。采用该方法成功地测定了昆明小鼠静脉注射外消旋布洛芬、(S)-(+)-布洛芬和(R)-(-)-布洛芬后布洛芬对映体的药代动力学。结果表明，(R)-(-)-布洛芬和(S)-(+)-布洛芬的药代动力学特征存在显著差异，表明R-(-)-布洛芬单向反转为(S)-(+)-布洛芬。

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来源期刊

Chirality 医学-分析化学

CiteScore

4.40

自引率

5.00%

发文量

124

审稿时长

1 months

期刊介绍： The main aim of the journal is to publish original contributions of scientific work on the role of chirality in chemistry and biochemistry in respect to biological, chemical, materials, pharmacological, spectroscopic and physical properties. Papers on the chemistry (physiochemical, preparative synthetic, and analytical), physics, pharmacology, clinical pharmacology, toxicology, and other biological aspects of chiral molecules will be published.