Memiş Hasan, Çakır Ahmet, Gün Zeynep Ülkü, Saraçoğlu Hatice, Karakükcü Çiğdem, Esmaoğlu Aliye, Doğan Zafer
Department of Clinical Pharmacy, İnönü University, Malatya, Türkiye.
Department of Clinical Pharmacy, Trakya University, Edirne, Türkiye.
Infect Dis Clin Microbiol. 2025 Jun 26;7(2):195-207. doi: 10.36519/idcm.2025.528. eCollection 2025 Jun.
Teicoplanin, a glycopeptide antibiotic, is used to treat infections caused by Gram-positive pathogens. Trough-level monitoring of teicoplanin is recommended in specific -patient populations, including critically ill patients. This study aimed to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify teicoplanin in human plasma and adapt the method to a critically ill patient sample.
Teicoplanin trough levels were measured using a newly validated LC-MS/MS method. Analysis was conducted using a C18 column with an inner diameter of 2.7 μm (50.0 x 3.0 mm), and vancomycin hydrochloride was used as the internal standard. The method's run time per sample was 5.5 minutes. Non-parametric tests were used for statistical analysis. Univariate and multivariate logistic regression were performed to identify teicoplanin target attainment factors. A -value of <0.05 was considered statistically significant.
The method demonstrated linearity between 1.56-100 mg/L teicoplanin concentration and had a lower limit of detection and quantification of 0.33 mg/L and 1.00 mg/L, respectively. Precision, accuracy, recovery rate, and carry-over effects were all within acceptable limits, according to the U.S. Food and Drug Administration (FDA) guidance. Twenty patients were included in the study. The target teicoplanin trough level (≥10 mg/L) attainment rate was 50%. The patient's laboratory values did not significantly change after teicoplanin treatment (>0.05), except for erythrocyte count, haemoglobin, and haematocrit values, which decreased significantly (<0.05). Multivariate analysis revealed no significant factors affecting target attainment (>0.05).
The LC-MS/MS assay validated in this study is high-throughput, robust, and quick enough to be implemented in clinical therapeutic drug monitoring (TDM) laboratories. More large-scale studies are needed to understand better the relationship between teicoplanin trough levels and patient-related factors.
替考拉宁是一种糖肽类抗生素，用于治疗革兰氏阳性病原体引起的感染。对于包括重症患者在内的特定患者群体，建议进行替考拉宁谷浓度监测。本研究旨在开发并验证一种液相色谱 - 串联质谱（LC-MS/MS）方法，用于定量测定人血浆中的替考拉宁，并使该方法适用于重症患者样本。
采用新验证的LC-MS/MS方法测定替考拉宁谷浓度。分析使用内径为2.7μm（50.0×3.0mm）的C18柱，以盐酸万古霉素作为内标。该方法每个样品的运行时间为5.5分钟。采用非参数检验进行统计分析。进行单因素和多因素逻辑回归以确定替考拉宁目标达成因素。P值<0.05被认为具有统计学意义。
该方法在替考拉宁浓度1.56 - 100mg/L之间呈线性，检测限和定量下限分别为0.33mg/L和1.00mg/L。根据美国食品药品监督管理局（FDA）指南，精密度、准确度、回收率和残留效应均在可接受范围内。本研究纳入了20名患者。替考拉宁谷浓度目标水平（≥10mg/L）达成率为50%。替考拉宁治疗后患者的实验室值除红细胞计数、血红蛋白和血细胞比容值显著下降（<0.05）外，其余均无显著变化（>0.05）。多因素分析显示无影响目标达成的显著因素（>0.05）。
本研究中验证的LC-MS/MS测定法具有高通量、稳健且快速的特点，足以在临床治疗药物监测（TDM）实验室中实施。需要更多大规模研究以更好地了解替考拉宁谷浓度与患者相关因素之间的关系。
