Antibiotic (ATB) treatment of critically ill patients with pathophysiological injuries remains a challenge due to the constant increase in antimicrobial resistance. Therapeutic drug monitoring (TDM) is advised for ATB dose adjustments to avoid suboptimal concentrations and dose-related adverse effects. Therefore, a single and reliable analytical method for a broad selection of ATBs was developed using a high-resolution mass spectrometry (HRMS) platform for frequent use in intensive care units.

An UHPLC assay coupled to high resolution accurate mass acquisition has been developed for the quantification of penicillins (amoxicillin, oxacillin, piperacillin, and ticarcillin), cephalosporines (cefepime, cefotaxime, ceftazidime, and ceftriaxone), carbapenems (ertapenem, imipenem, and meropenem), lincosamide (clindamycin), quinolones (ofloxacin and ciprofloxacin) and tazobactam. Plasma samples (100 μL) were spiked with an internal standard solution followed by protein precipitation. Separation was achieved on an Accucore C18 column, which enabled sample analysis every 9 min.

All compounds were detected in electrospray positive ion mode and quantified with a linear regression between 0.5 and 32 mg/L (r2 > 0.998). Overall precision and accuracy did not exceed 15%. No significant matrix effect was observed for the studied ATBs. Stored stock solutions at −20 °C were stable for 6 months, except for amoxicillin and imipenem. Analytes in plasma were stable for 24 h under ambient conditions as well as in post-preparation in an autosampler, except for amoxicillin and imipenem.

This HRMS assay provides the simultaneous quantification of 15 ATB; it fulfills the usual quality criteria and was successfully applied for routine TDM of ATBs. The method is based on a full scan acquisition, and it would be easy to add other compounds to the present panel in the future, as this assay has already been proven to be efficient for different classes of compounds.

由于抗菌素耐药性的不断提高，对具有病理生理学损伤的重症患者进行抗生素（ATB）治疗仍然是一个挑战。建议对治疗药物监测（TDM）进行ATB剂量调整，以避免浓度欠佳和剂量相关的不良反应。因此，使用高分辨率质谱（HRMS）平台开发了用于广泛选择ATB的单一且可靠的分析方法，以在重症监护病房中频繁使用。

已开发出一种结合了高分辨率精确质量获取的UHPLC测定法，用于定量测定青霉素（阿莫西林，奥沙西林，哌拉西林和替卡西林），头孢菌素（头孢吡肟，头孢噻肟，头孢他啶和头孢曲松），碳青霉烯（ertapenem，亚胺培南， ，林可酰胺（克林霉素），喹诺酮类（氧氟沙星和环丙沙星）和他唑巴坦。将血浆样品（100μL）掺入内标溶液，然后进行蛋白质沉淀。在Accucore C18色谱柱上实现了分离，该色谱柱每9分钟进行一次样品分析。

所有化合物均以电喷雾正离子模式检测，并以0.5至32 mg / L之间的线性回归进行定量（r2> 0.998）。总体精度和准确度不超过15％。对于所研究的ATB，没有观察到明显的基质效应。除阿莫西林和亚胺培南外，在-20°C下储存的储备溶液可稳定保存6个月。除阿莫西林和亚胺培南外，血浆中的分析物在环境条件下以及在自动进样器中的制备后均稳定24小时。

该HRMS测定可同时定量15 ATB；它符合通常的质量标准，并已成功应用于ATB的常规TDM。该方法基于全扫描采集，将来很容易将其他化合物添加到目前的面板中，因为该测定方法已被证明对不同种类的化合物有效。