Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jan 1;878(1):39-44. doi: 10.1016/j.jchromb.2009.11.017.
Fungal infections occur in immunocompromised patients. Azole antifungal agents are used for the prophylaxis and treatment of these infections. The interest in therapeutic drug monitoring azole agents has increased over the last few years. Inter- and intra-patient variability of pharmacokinetics, drug-drug interactions, serum concentration related toxicity and success of therapy has stressed the need of frequently therapeutic drug monitoring of the drugs, belonging to the group of azoles. Therefore a simple, rapid and flexible method of analysis is required. This method is based on the precipitation of proteins in human serum with LC/MS/MS detection. Validation was performed according to the guidelines for bioanalytical method validation of the food and drug administration agency. The four most used azole drugs can be detected in human serum within the clinical relevant serum levels with good accuracy and reproducibility at the limit of quantification. Intra- and inter-day validation demonstrated good accuracy and reproducibility. A rapid, sensitive and flexible LC/MS/MS method has been developed and validated to measure voriconazole (VRZ), fluconazole (FLZ), itraconazole (ITZ) and posaconazole (PSZ) in human serum. This new method is suitable for clinical pharmacokinetic studies and routine monitoring in daily practice.
真菌感染发生于免疫功能低下的患者。唑类抗真菌药物被用于这些感染的预防和治疗。近年来，人们对唑类药物治疗药物监测的兴趣有所增加。药代动力学的个体内和个体间差异、药物相互作用、与血清浓度相关的毒性以及治疗的成功，强调了经常监测属于唑类药物的药物的治疗药物浓度的必要性。因此，需要一种简单、快速和灵活的分析方法。本方法基于 LC/MS/MS 检测的人血清中蛋白质的沉淀。验证是根据食品和药物管理局的生物分析方法验证指南进行的。可以在临床相关的血清浓度范围内检测到四种最常用的唑类药物，在定量限下具有良好的准确性和重现性。日内和日间验证证明了良好的准确性和重现性。已经开发和验证了一种快速、灵敏和灵活的 LC/MS/MS 方法，用于测量人血清中的伏立康唑（VRZ）、氟康唑（FLZ）、伊曲康唑（ITZ）和泊沙康唑（PSZ）。这种新方法适用于临床药代动力学研究和日常实践中的常规监测。
