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Daptomycin determination by liquid chromatography-mass spectrometry in peritoneal fluid, blood plasma, and urine of clinical patients receiving peritoneal dialysis treatment

机译:液相色谱-质谱法测定腹膜透析患者临床腹膜液,血浆和尿中达托霉素的含量

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摘要

A 13-min LC-MS method was developed for the determination of daptomycin, a new potent antibiotic, in peritoneal fluid, blood plasma, and urine of patients receiving renal replacement therapy. Chromatography was performed on a C _(18) column and detection was performed by a single-quadrupole mass spectrometer coupled to LC via an electrospray interface (ESI). The column effluent was also monitored at 370 nm using a photodiode-array detector. The developed method provided a linear dynamic range for concentrations from 0.5 μg mL~(-1) to 100 μg mL~(-1). Method precision and accuracy were found to be satisfactory for clinical application, thus the method was successfully used for the analysis of daptomycin in pharmacokinetic studies. The drug was preventively administered against Gram-positive infections to 19 clinical patients undergoing peritoneal dialysis. Peritoneal fluid, blood plasma, and urine samples were collected at 13 time points over a period of 48 h. Clinical samples were analysed following simple sample-preparation procedures and daptomycin was unambiguously detected and quantified.
机译:开发了一种13分钟的LC-MS方法,用于测定接受肾脏替代疗法的患者腹膜液,血浆和尿液中的达托霉素(一种新的有效抗生素)。在C _(18)色谱柱上进行色谱分析,并通过电喷雾接口(ESI)连接到LC的单四极杆质谱仪进行检测。还使用光电二极管阵列检测器在370 nm处监测柱流出物。所开发的方法为0.5μgmL〜(-1)至100μgmL〜(-1)的浓度提供了线性动态范围。方法精密度和准确性被发现对于临床应用是令人满意的,因此该方法已成功用于药物动力学研究中的达托霉素分析。该药物已针对19例接受腹膜透析的临床患者预防性地预防了革兰氏阳性感染。在48小时内的13个时间点收集腹膜液,血浆和尿液样本。按照简单的样品制备程序对临床样品进行分析,并明确检测和定量达托霉素。

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