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建立并验证 UPLC-MS/MS 法同时测定人血浆中左氧氟沙星、环丙沙星、莫西沙星和利福平的浓度:在骨关节感染治疗药物监测中的应用。

Development and validation of a UPLC-MS/MS method for simultaneous quantification of levofloxacin, ciprofloxacin, moxifloxacin and rifampicin in human plasma: Application to the therapeutic drug monitoring in osteoarticular infections.

机构信息

AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, F-75013 Paris, France.

AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, F-75013 Paris, France; Sorbonne Université Médecine, INSERM CIC Paris-Est, AP-HP, ICAN, Pitié-Salpêtrière Hospital, Department of Pharmacology, F-75013 Paris, France.

出版信息

J Pharm Biomed Anal. 2020 May 10;183:113137. doi: 10.1016/j.jpba.2020.113137. Epub 2020 Feb 1.

DOI:10.1016/j.jpba.2020.113137
PMID:32086125
Abstract

BACKGROUND

Fluoroquinolones and rifampicin are antibiotics frequently used for the treatment of osteoarticular infections, and their therapeutic drug monitoring is recommended. The aim of this study was to develop and validate a rapid and selective method of simultaneous quantification of levofloxacin, ciprofloxacin, moxifloxacin and rifampicin with short pretreatment and run times in order to be easily used in clinical practice.

METHODS

After a simple protein precipitation of plasma samples, the chromatographic separation was performed using an ultra-performance liquid chromatography system coupled with mass tandem spectrometry in a positive ionization mode. The mobile phase consisted of a gradient elution of water-formic acid (100:0.1, v/v)-ammonium acetate 2 mM (A) and methanol-formic acid (100:0.1, v/v)-ammonium acetate 2 mM (B) at a flow rate at 0.3 mL/min.

RESULTS

Analysis time was 5 min per run, and all analytes and internal standards eluted within 0.85-1.69 minutes. The calibration curves were linear over the range from 0.5-30 μg/mL for levofloxacin, ciprofloxacin, moxifloxacin and rifampicin with linear regression coefficients above 0.995 for all analytes. The intra-day and inter-day coefficients of variation were below 10 % for lower and higher concentration. This method was successfully applied to drug monitoring in patients with an osteoarticular infection.

CONCLUSION

A simple, rapid, and selective liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of levofloxacin, ciprofloxacin, moxifloxacin and rifampicin in human plasma.

摘要

背景

氟喹诺酮类和利福平是常用于治疗骨关节炎感染的抗生素,推荐进行治疗药物监测。本研究旨在开发和验证一种快速、选择性的方法,同时定量检测人血浆中的左氧氟沙星、环丙沙星、莫西沙星和利福平,预处理和运行时间短,以便于在临床实践中使用。

方法

对血浆样品进行简单的蛋白沉淀后,采用超高效液相色谱-串联质谱系统,在正离子模式下进行色谱分离。流动相由水-甲酸(100:0.1,v/v)-2 mM 乙酸铵(A)和甲醇-甲酸(100:0.1,v/v)-2 mM 乙酸铵(B)梯度洗脱,流速为 0.3 mL/min。

结果

分析时间为 5 分钟/次,所有分析物和内标均在 0.85-1.69 分钟内洗脱。左氧氟沙星、环丙沙星、莫西沙星和利福平的校准曲线在 0.5-30μg/mL 范围内呈线性,所有分析物的线性回归系数均大于 0.995。日内和日间变异系数均低于 10%,用于较低和较高浓度的检测。该方法成功应用于骨关节炎感染患者的药物监测。

结论

开发并验证了一种简单、快速、选择性的液相色谱-串联质谱法,用于同时定量检测人血浆中的左氧氟沙星、环丙沙星、莫西沙星和利福平。

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