Swoboda Stefanie, Ober Michael, Anagnostakos Konstantinos, Geiss Heinrich K, Weigand Markus A, Hoppe-Tichy Torsten
Pharmacy Department, University of Heidelberg, Heidelberg, Germany.
Clin Chem Lab Med. 2007;45(8):1019-22. doi: 10.1515/CCLM.2007.247.
Linezolid is an important therapeutic option for the treatment of infections caused by multiresistant Gram-positive bacteria such as vancomycin-resistant Enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). However, the clinical benefit of linezolid is threatened by the emergence of resistant strains of MRSA and VRE reported in North America and Europe. For effective antimicrobial treatment, it is extremely important to have exact knowledge of drug concentrations at the site of action.
A simple HPLC method for the rapid and precise determination of linezolid in different biomatrices (e.g., plasma, soft tissue, bone, dialysis fluid and used microbiological broth) was developed and validated. Proteins were precipitated with acetonitrile and separation was performed on a reversed-phase C8 column with a mobile phase consisting of water/acetonitrile (80:20, v/v). UV detection was performed at 251 nm.
This method has a lower limit of quantification of 0.3 microg/mL and a linear calibration range of 0.5-40 microg/mL. The method showed excellent reproducibility, with an inter- and intra-day assay precision of <5% (% relative standard deviation), as well as excellent accuracy, with inter- and intra-day assay accuracy ranging from 100.6% to 103.2%. Stability up to 6 months in water and plasma was proven. Quantitative recovery was possible after up to three freeze thaw cycles.
The method is useful in the acquisition of in vivo and in vitro data. It is simple, flexible, specific, precise and reproducible, as well as of adequate sensitivity for clinical use.
利奈唑胺是治疗由多重耐药革兰氏阳性菌引起的感染的重要治疗选择，如耐万古霉素肠球菌（VRE）和耐甲氧西林金黄色葡萄球菌（MRSA）。然而，北美和欧洲报道的MRSA和VRE耐药菌株的出现威胁到了利奈唑胺的临床疗效。为了进行有效的抗菌治疗，准确了解作用部位的药物浓度极为重要。
开发并验证了一种简单的高效液相色谱法，用于快速、精确地测定不同生物基质（如血浆、软组织、骨、透析液和用过的微生物肉汤）中的利奈唑胺。用乙腈沉淀蛋白质，并在反相C8柱上进行分离，流动相由水/乙腈（80:20，v/v）组成。在251nm处进行紫外检测。
该方法的定量下限为0.3μg/mL～，线性校准范围为0.5～40μg/mL。该方法具有出色的重现性，日内和日间测定精密度<5%（相对标准偏差%），以及出色的准确度，日内和日间测定准确度范围为100.6%至103.2%。已证明在水和血浆中长达6个月的稳定性。经过多达三个冻融循环后仍可进行定量回收。
该方法有助于获取体内和体外数据。它简单、灵活、特异、精确且可重现，并且具有足够的临床使用灵敏度。
