Unidad de Gestión Clínica de Farmacia, Hospital Universitario Virgen del Rocío/CSIC/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.
Unidad de Gestión Clínica de Farmacia, Hospital Universitario Virgen del Rocío/CSIC/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.
J Pharm Biomed Anal. 2020 Sep 10;189:113484. doi: 10.1016/j.jpba.2020.113484. Epub 2020 Jul 21.
Ceftriaxone is a third-generation cephalosporin, worldwide use as a first-line treatment for several infections, including life-threatening infections as meningitis or endocarditis. Nowadays, ceftriaxone use is changing, embracing high-dose schemes, new populations treated and requirement of dose individualization and optimization. These reasons warranted the development of new sensitive assays. This study aimed to develop and validate a fast and handy bioanalytical method for the quantification of ceftriaxone in human plasma covering a broad range of concentrations. The analysis was performed using high-performance liquid chromatography coupled to tandem mass spectrometry. Sample preparation was based on protein precipitation with acetonitrile followed by centrifugation. Chromatography separation was performed on Phenomenex Luna C18 column (5 μm, 150 × 2.0 mm) and a mobile phase consisting of 70 % of mobile phase A (10 mM of ammonium acetate and 1% formic acid in purified water) and 30 % mobile phase B (0.1 % formic acid in acetonitrile) at a flow rate of 500 μl/min on an isocratic program. Both the analyte and the internal standard were quantified using the positive electrospray ionization (ESI) mode within a single runtime of 5.00 min. The method was validated following the U.S. Food and Drug Administration guidelines over the concentration range of 3-1000 μg/mL. The within-run and between-run precision and accuracy were <15 %, and therefore met the standard regulatory acceptance criterion. In conclusion, a sensitive and robust LC-MS/MS method was developed for a fast quantitation of ceftriaxone concentrations in plasma samples with multiples applications in research and clinical therapeutic drug monitoring.
头孢曲松是一种第三代头孢菌素，在世界范围内被用作多种感染的一线治疗药物，包括危及生命的感染，如脑膜炎或心内膜炎。如今，头孢曲松的使用正在发生变化，包括采用高剂量方案、治疗新人群以及需要个体化和优化剂量。这些原因促使开发新的敏感检测方法。本研究旨在开发和验证一种快速简便的生物分析方法，用于定量检测人血浆中的头孢曲松，涵盖广泛的浓度范围。分析采用高效液相色谱-串联质谱法进行。样品制备采用乙腈沉淀蛋白，然后离心。色谱分离在 Phenomenex Luna C18 柱（5 μm，150×2.0 mm）上进行，流动相由 70%流动相 A（10 mM 乙酸铵和 1%甲酸在纯化水中）和 30%流动相 B（0.1%甲酸在乙腈中）组成，流速为 500 μl/min，采用等度程序。在单个运行时间内 5.00 min 内，使用正电喷雾电离（ESI）模式同时定量分析物和内标。该方法按照美国食品和药物管理局的指南进行验证，浓度范围为 3-1000 μg/mL。批内和批间精密度和准确度均<15%，因此符合标准监管接受标准。总之，开发了一种灵敏且稳健的 LC-MS/MS 方法，用于快速定量检测血浆样品中的头孢曲松浓度，可应用于研究和临床治疗药物监测。
