Simple LC-MS/MS Methods Using Core–Shell Octadecylsilyl Microparticulate for the Quantitation of Total and Free Daptomycin in Human Plasma
Simple LC-MS/MS Methods Using Core–Shell Octadecylsilyl Microparticulate for the Quantitation of Total and Free Daptomycin in Human Plasma
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DOI：
10.1097/ftd.0000000000000535
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发表时间：
2018-10
影响因子：
2.5
通讯作者：
Yukari Miyadera;T. Naito;Takahiro Yamada;J. Kawakami
中科院分区：
文献类型：
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作者：
Yukari Miyadera;T. Naito;Takahiro Yamada;J. Kawakami
背景：达托霉素是一种环脂肽类抗生素，具有高血浆蛋白结合率。本研究开发了一种简单的液相色谱分离方法，使用核-壳十八烷基硅烷基微粒耦合串联质谱法定量人血浆中的总和游离达托霉素。方法：采用离心超滤法获得血浆中游离达托霉素。采用等度洗脱的核-壳十八烷基硅微粒直接分离去蛋白血浆标本。质谱仪以正离子电喷雾电离模式运行。该方法用于定量静脉注射达托霉素患者的血浆样品。结果：达托霉素和地西泮作为内标被洗脱，总运行时间为10分钟。人血浆中总达托霉素和游离达托霉素的校准曲线分别在1-100和0.1-10 mcg/mL浓度范围内呈线性。人血浆中总达托霉素和游离达托霉素的定量下限分别为1.0和0.1 mcg/mL。在未过滤和超滤血浆样品中的提取回收率分别为106.1%和98.2%。总达托霉素和游离达托霉素在人血浆中未表现出任何基质效应。总达托霉素的日内和日间准确度和不精密度分别为88.7%~ 106.0%和98.7%~ 105.9%，在4.1%和10.4%以内;游离达托霉素的日内和日间准确度和不精密度分别为86.8%~ 101.6%和103.0%~ 107.8%，在14.6%和14.6%以内。15例感染患者的总达托霉素和游离达托霉素血浆浓度范围分别为3.01-34.1和0.39-3.64 mcg/mL。达托霉素的血浆蛋白结合率范围为80.8%-94.9%。结论：本方法简单，分析性能可接受，可用于监测达托霉素在临床感染患者中的药代动力学。
Background: Daptomycin, a cyclic lipopeptide antibiotic, displays high plasma protein binding. This study developed the simple method of liquid chromatographic separation using a core–shell octadecylsilyl microparticulate coupled to tandem mass spectrometry for the quantitation of total and free daptomycin in human plasma. Methods: Free daptomycin in plasma was obtained by centrifugal ultrafiltration. Deproteinized plasma specimens were directly separated using a core–shell octadecylsilyl microparticulate with isocratic elution. The mass spectrometer was run in positive-ion electrospray ionization mode. This method was applied to the quantitation of plasma samples in patients treated with intravenous daptomycin. Results: Daptomycin and diazepam as an internal standard were eluted with a total run time of 10 minutes. The calibration curves of total and free daptomycin in human plasma were linear over the concentration ranges of 1–100 and 0.1–10 mcg/mL, respectively. The lower limits of quantitation of the total and free daptomycin in human plasma were 1.0 and 0.1 mcg/mL, respectively. Their extraction recovery rates in nonfiltrated and ultrafiltrated plasma samples were 106.1% and 98.2%, respectively. Total and free daptomycin did not exhibit any matrix effects in human plasma. The intraday and interday accuracies and imprecisions of total daptomycin were 88.7%–106.0% and 98.7%–105.9%, and within 4.1% and 10.4%, whereas those of free daptomycin were 86.8%–101.6% and 103.0%–107.8%, and within 14.6% and 14.6%, respectively. The plasma concentration ranges of total and free daptomycin in 15 infected patients were 3.01–34.1 and 0.39–3.64 mcg/mL, respectively. The plasma protein binding rate of daptomycin ranged from 80.8% to 94.9%. Conclusions: The present simple method with an acceptable analytical performance can be helpful for monitoring the pharmacokinetics of daptomycin in infected patients observed in clinical settings.