Abstract：
BACKGROUND: Therapeutic drug monitoring (TDM) for antibiotic drugs represents a consolidated practice to optimize the effectiveness and to limit the toxicity of specific drugs by guiding dosage adjustments. The comparison of TDM results with drug-specific pharmacokinetic/pharmacodynamic (PK/PD) parameters, based on killing dynamics and bacterial susceptibility, increases the probability of therapeutic success.
OBJECTIVE: The aim of this study was the analytical validation of a new UHPLC-MS/MS assay for the quantification of 19 antibiotics divided in two different sets considering their chemical/pharmacological properties. This method has been implemented in an analytical LC-MS/MS Kit System by CoQua Lab s.r.l (Turin).
METHODS: The analytical validation is developed in accordance with \"ICH Harmonized Guideline M10 on bioanalytical method validation and study sample analysis\" and \"Guidelines for regulatory auditing of quality management system of medical device manufacturers\". Method suitability in the clinical context was tested by analysing clinical samples from patients treated with antibiotic drugs.
RESULTS: This method allows for simultaneous TDM of the following molecules: dalbavancin, daptomycin, linezolid, tedizolid, levofloxacin, moxifloxacin, meropenem, ertapenem, vaborbactam, avibactam, sulbactam, tazobactam, ceftazidime, ceftriaxone, ceftolozane, ceftobiprole, cefiderocol, ceftaroline and piperacillin. These drugs were quantified showing analytical performance parameters compliant with guidelines in terms of repeatability, reproducibility, robustness, bias, LOD, LOQ and linearity. The method was capable to successfully monitor drug concentrations in 65 samples from 52 patients undergoing treatment.
CONCLUSIONS: The UHPLC-MS/MS method described in this work can be useful for TDM of the reported antimicrobial agents. The analytical protocol is rapid and suitable to be used in routine analysis.
OBJECTIVE: The aim of this study was the analytical validation of a new UHPLC-MS/MS assay for the quantification of 19 antibiotics divided in two different sets considering their chemical/pharmacological properties. This method has been implemented in an analytical LC-MS/MS Kit System by CoQua Lab s.r.l (Turin).
METHODS: The analytical validation is developed in accordance with \"ICH Harmonized Guideline M10 on bioanalytical method validation and study sample analysis\" and \"Guidelines for regulatory auditing of quality management system of medical device manufacturers\". Method suitability in the clinical context was tested by analysing clinical samples from patients treated with antibiotic drugs.
RESULTS: This method allows for simultaneous TDM of the following molecules: dalbavancin, daptomycin, linezolid, tedizolid, levofloxacin, moxifloxacin, meropenem, ertapenem, vaborbactam, avibactam, sulbactam, tazobactam, ceftazidime, ceftriaxone, ceftolozane, ceftobiprole, cefiderocol, ceftaroline and piperacillin. These drugs were quantified showing analytical performance parameters compliant with guidelines in terms of repeatability, reproducibility, robustness, bias, LOD, LOQ and linearity. The method was capable to successfully monitor drug concentrations in 65 samples from 52 patients undergoing treatment.
CONCLUSIONS: The UHPLC-MS/MS method described in this work can be useful for TDM of the reported antimicrobial agents. The analytical protocol is rapid and suitable to be used in routine analysis.
摘要：
背景：抗生素药物的治疗药物监测（TDM）代表了通过指导剂量调整来优化有效性和限制特定药物毒性的综合实践。TDM结果与药物特异性药代动力学/药效学（PK/PD）参数的比较，基于杀灭动力学和细菌敏感性，增加治疗成功的可能性。
目的：本研究的目的是对一种新的UHPLC-MS/MS测定法进行分析验证，该测定法可根据其化学/药理特性分为两组，对19种抗生素进行定量。该方法已在CoQuaLabs.r.l(Turin)的分析型LC-MS/MS试剂盒系统中实施。
方法：分析验证是根据“ICH关于生物分析方法验证和研究样品分析的协调指南M10”和“医疗器械制造商质量管理体系监管审核指南”制定的。通过分析来自用抗生素药物治疗的患者的临床样品来测试方法在临床环境中的适用性。
结果：该方法允许以下分子的同时TDM：dalbavancin，达托霉素,利奈唑胺,替迪唑胺,左氧氟沙星,莫西沙星,美罗培南,厄他培南,vaborbactam,阿维巴坦,舒巴坦,他唑巴坦,头孢他啶,头孢曲松,头孢洛赞,头孢比宝,cefiderocol,头孢洛林和哌拉西林.对这些药物进行了量化，显示出在可重复性方面符合指南的分析性能参数，再现性，鲁棒性，偏见，LOD,LOQ和线性度。该方法能够成功监测来自52名接受治疗的患者的65个样品中的药物浓度。
结论：这项工作中描述的UHPLC-MS/MS方法可用于报道的抗微生物剂的TDM。分析方案是快速的，适合用于常规分析。
目的：本研究的目的是对一种新的UHPLC-MS/MS测定法进行分析验证，该测定法可根据其化学/药理特性分为两组，对19种抗生素进行定量。该方法已在CoQuaLabs.r.l(Turin)的分析型LC-MS/MS试剂盒系统中实施。
方法：分析验证是根据“ICH关于生物分析方法验证和研究样品分析的协调指南M10”和“医疗器械制造商质量管理体系监管审核指南”制定的。通过分析来自用抗生素药物治疗的患者的临床样品来测试方法在临床环境中的适用性。
结果：该方法允许以下分子的同时TDM：dalbavancin，达托霉素,利奈唑胺,替迪唑胺,左氧氟沙星,莫西沙星,美罗培南,厄他培南,vaborbactam,阿维巴坦,舒巴坦,他唑巴坦,头孢他啶,头孢曲松,头孢洛赞,头孢比宝,cefiderocol,头孢洛林和哌拉西林.对这些药物进行了量化，显示出在可重复性方面符合指南的分析性能参数，再现性，鲁棒性，偏见，LOD,LOQ和线性度。该方法能够成功监测来自52名接受治疗的患者的65个样品中的药物浓度。
结论：这项工作中描述的UHPLC-MS/MS方法可用于报道的抗微生物剂的TDM。分析方案是快速的，适合用于常规分析。
