Department of Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland.
Ann Lab Med. 2024 Mar 1;44(2):174-178. doi: 10.3343/alm.2023.0250. Epub 2023 Oct 23.
Antibiotic therapy requires appropriate dosage of drugs for effective treatment. Too low antibiotic concentrations may lead to treatment failure and the development of resistant pathogens, whereas overdosing may cause neurological side effects or hemolytic diseases. Meropenem and linezolid are used only in the treatment of serious infections or when other antibiotics are no longer effective as well as for treating central nervous system infections. It is difficult or sometimes even impossible to predict the relation between dosing of antibiotics and its cerebrospinal fluid (CSF) concentration; thus, a method of determining antibiotics not only in the blood but also in the CSF is needed. Analytical method validation is an integral part of good laboratory practice and ensures high accuracy of the results. We performed complete validation process according to the Food and Drug Administration and European Medicine Agency, covering the aspects precision, specificity, accuracy, recovery, limit of detection, limit of quantification, stability, carry-over, and matrix effects. Our liquid chromatography-tandem mass spectrometry method for the simultaneous measurement of meropenem and linezolid in different matrix meets all the acceptance criteria. The method was successfully applied to determine meropenem and linezolid concentrations in serum and CSF samples obtained from children treated with these antibiotics.
抗生素治疗需要适当的药物剂量才能有效治疗。抗生素浓度过低可能导致治疗失败和耐药病原体的产生，而剂量过高可能会导致神经系统副作用或溶血性疾病。美罗培南和利奈唑胺仅用于治疗严重感染或其他抗生素无效以及治疗中枢神经系统感染。很难甚至不可能预测抗生素剂量与其脑脊液（CSF）浓度之间的关系；因此，需要一种既能在血液中又能在 CSF 中测定抗生素的方法。分析方法验证是良好实验室规范的一个组成部分，可确保结果的高度准确性。我们按照美国食品和药物管理局和欧洲药品管理局的要求进行了完整的验证过程，涵盖了精密度、特异性、准确性、回收率、检测限、定量限、稳定性、携带污染和基质效应等方面。我们的液相色谱-串联质谱法用于同时测量不同基质中的美罗培南和利奈唑胺，符合所有验收标准。该方法已成功应用于测定接受这些抗生素治疗的儿童的血清和 CSF 样本中的美罗培南和利奈唑胺浓度。
