Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Anal Toxicol. 2010 Apr;34(3):135-41. doi: 10.1093/jat/34.3.135.
Moxifloxacin (MFX) is a useful agent in the treatment of multi-drug-resistant tuberculosis (MDR-TB). At Tuberculosis Centre Beatrixoord, a referral center for tuberculosis in the Netherlands, approximately 36% of the patients have received MFX as treatment. Based on the variability of MFX AUC, the variability of in vitro susceptibility to MFX of M. tuberculosis, and the variability of penetration into sanctuary sites, measuring the concentration of MFX in plasma and cerebrospinal fluid (CSF) could be recommended. Therefore, a rapid and validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) analyzing method with a simple pretreatment procedure was developed for therapeutic drug monitoring of MFX in human plasma and CSF. Because of the potential influence of protein binding on efficacy, we decided to determine both bound and unbound (ultrafiltrate) fraction of MFX. The calibration curves were linear in the therapeutic range of 0.05 to 5.0 mg/L plasma and CSF with CV in the range of -5.4% to 9.3%. MFX ultrafiltrate samples could be determined with the same method setup for analysis of MFX in CSF. The LC-MS-MS method developed in this study is suitable for monitoring MFX in human plasma, plasma ultrafiltrate, and CSF.
莫西沙星（MFX）是治疗耐多药结核病（MDR-TB）的有效药物。在荷兰结核病中心 Beatrixoord，这是一家结核病转诊中心，约有 36%的患者接受 MFX 治疗。基于 MFX AUC 的可变性、结核分枝杆菌对 MFX 体外敏感性的可变性以及进入避难所部位的可变性，建议测量 MFX 在血浆和脑脊液（CSF）中的浓度。因此，开发了一种快速且经过验证的液相色谱-串联质谱（LC-MS-MS）分析方法，具有简单的预处理程序，用于人血浆和 CSF 中 MFX 的治疗药物监测。由于蛋白结合对疗效的潜在影响，我们决定同时测定 MFX 的结合和未结合（超滤）部分。在 0.05 至 5.0 mg/L 血浆和 CSF 的治疗范围内，校准曲线呈线性，CV 范围为-5.4%至 9.3%。MFX 超滤样品可以用相同的方法设置来分析 CSF 中的 MFX。本研究中开发的 LC-MS-MS 方法适用于监测人血浆、血浆超滤物和 CSF 中的 MFX。
