Therapeutic Drug Monitoring of Protein Unbound Ciprofloxacin Concentrations to avoid inadequate Treatment of severe Bacterial Infections in Critically ill Patients

Journal of Applied Bioanalysis Pub Date : 2018-12-31 DOI:10.17145/JAB.18.021

Noortje J D Mabelis, Kimberly N. Shudofsky, J. J. V. Raaij, S. Meenks, T. Havenith, S. Croes, J. L. L. Noble, P. Janssen

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引用次数: 1

Abstract

OBJECTIVES: To develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for therapeutic drug monitoring (TDM) of unbound ciprofloxacin concentrations in critically ill patients. METHODS: Total and unbound ciprofloxacin concentrations of five randomly selected intensive care unit (ICU) patients were measured using UPLC-MS/MS. Method validation included accuracy, linearity, precision, repeatability, and limits of detection and quantification. RESULTS: The median unbound ciprofloxacin fraction was 74.8%, with a median area under the curve from 0-24 h (AUC0-24) and maximum serum concentration (Cmax) of 28.51 h·mg/L and 4.45 mg/L respectively. Median free AUC0-24 (fAUC0-24) and free Cmax (fCmax) were 21.57 h·mg/L and 3.53 mg/L respectively; 20% of patients reached the pharmacodynamic target. The UPLC-MS/ MS method was validated using an intra-assay and inter-assay precision < 3%. Recoveries were between 90-110% CONCLUSIONS: This UPLC-MS/MS method provided reliable unbound ciprofloxacin concentrations, allowing target attainment in critically ill patients and exploration of different dosing regimens.

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治疗药物监测蛋白未结合环丙沙星浓度避免危重病人严重细菌感染治疗不足

目的:建立一种可靠的超高效液相色谱-串联质谱(UPLC-MS/MS)监测危重患者非结合环丙沙星治疗药物浓度(TDM)方法。方法:随机选择5例重症监护病房(ICU)患者，采用超高效液相色谱-质谱联用仪(UPLC-MS/MS)测定其环丙沙星总浓度和非结合浓度。方法验证包括准确性、线性度、精密度、重复性、检测限和定量限。结果:环丙沙星游离分数中位数为74.8%，0 ~ 24 h曲线下面积中位数(auc0 ~ 24)，最大血药浓度(Cmax)分别为28.51 h·mg/L和4.45 mg/L。中位游离AUC0-24 (fAUC0-24)和游离Cmax (fCmax)分别为21.57 h·mg/L和3.53 mg/L;20%的患者达到药效学指标。UPLC-MS/ MS方法的分析内和分析间精密度< 3%。结论:该UPLC-MS/MS方法可提供可靠的非结合环丙沙星浓度，可达到危重患者的目标，并可探索不同给药方案。

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来源期刊

Journal of Applied Bioanalysis

CiteScore

1.00

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0.00%

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