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Quantification of anidulafungin and micafungin in human body fluids by high performance-liquid chromatography with UV-detection.
Journal of Chromatography B ( IF 2.8 ) Pub Date : 2019-12-12 , DOI: 10.1016/j.jchromb.2019.121937
René Welte 1 , Herbert Oberacher 2 , Bernhard Schwärzler 1 , Michael Joannidis 3 , Romuald Bellmann 1
Affiliation  

The echinocandins anidulafungin (ANID) and micafungin (MICA) are recommended for treatment of invasive Candida infections. As target-site concentrations of antimicrobial agents are crucial for eradication of pathogens, we established and validated high-performance liquid chromatography-UV detection (HPLC-UV) assays for quantification of ANID and MICA in human plasma, ascites fluid, pleural effusion, and in cerebrospinal fluid (CSF). Sample pre-purification was performed by protein precipitation with acetonitrile followed by solid phase extraction. For both assays, intra- and interday precision, and accuracy fulfilled the requirements for bioanalytical methods issued by the European Medicine Agency (EMA). The lower limit of quantification was 0.01 mg/L for both drugs. At 25 °C, ANID and MICA concentrations declined by up to 70% within 24 h. Concentrations remained stable over 24 h at 4 °C and over four weeks at -80 °C. In conclusion, the developed methods are fit for the assessment of target-site pharmacokinetics of ANID and MICA in clinical studies.

中文翻译:

使用紫外检测的高效液相色谱法对人体体液中的阿尼芬净和米卡芬净进行定量。

棘白菌素阿尼芬净 (ANID) 和米卡芬净 (MICA) 被推荐用于治疗侵袭性念珠菌感染。由于抗菌剂的靶点浓度对于根除病原体至关重要,因此我们建立并验证了高效液相色谱-紫外检测 (HPLC-UV) 检测方法,用于量化人血浆、腹水、胸腔积液和胸腔积液中的 ANID 和 MICA在脑脊液 (CSF) 中。通过用乙腈沉淀蛋白质然后固相萃取来进行样品预纯化。对于这两种分析,日内和日间精密度和准确度均满足欧洲药品管理局 (EMA) 对生物分析方法的要求。两种药物的定量下限均为 0.01 mg/L。在 25 °C 下,ANID 和 MICA 浓度在 24 小时内下降了 70%。浓度在 4 °C 下保持稳定超过 24 小时,在 -80 °C 下保持超过 4 周。总之,所开发的方法适用于临床研究中评估 ANID 和 MICA 的靶点药代动力学。
更新日期:2019-12-13
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