Institute of Pharmacology, Hannover Medical School, Hannover, Germany.
Clin Chim Acta. 2012 Jan 18;413(1-2):240-5. doi: 10.1016/j.cca.2011.09.042. Epub 2011 Oct 6.
Fluconazole, itraconazole, posaconazole and voriconazole are four triazole antifungal drugs administered for the prevention and in the treatment of invasive fungal infections. Therapeutic drug monitoring of these antifungals in human plasma is advised.
After protein precipitation by adding methanol/ZnSO(4) containing ketoconazole as internal standard (IS) the analytes were isolated from matrix and enriched by solid-phase extraction (SPE) and were separated on an Allure PFP HPLC column, maintained at 60°C. The retention times were 1.12, 1.09, 1.09, 1.15 and 1.94 min for fluconazole, voriconazole, posaconazole, itraconazole and ketoconazole, respectively. Cycle time was 3 min, injection to injection. The analytes were monitored by means of a tandem mass spectrometer. Selected reaction monitoring (SRM) in positive ion mode was used for quantitation.
The presented method has limits of detection of 2-10 ng/mL, a lower limit of quantitation of 14 ng/mL and linearities ≥0.999 for the different analytes. The intra- and interday correlation coefficients of variation were <8.1 and <9.8%, respectively. The accuracy ranged from 85 to 106%.
A rapid, sensitive, and robust HPLC-MS/MS method for quantifying fluconazole, itraconazole, posaconazole and voriconazole levels in human plasma was validated and successfully applied to samples from antifungal treated patients.
氟康唑、伊曲康唑、泊沙康唑和伏立康唑是四种用于预防和治疗侵袭性真菌感染的三唑类抗真菌药物。建议对这些抗真菌药物在人血浆中的治疗药物监测。
用甲醇/ZnSO 4 沉淀蛋白，加入酮康唑作为内标（IS），将分析物从基质中分离出来，用固相萃取（SPE）进行富集，并在 Allure PFP HPLC 柱上分离，柱温为 60°C。氟康唑、伏立康唑、泊沙康唑、伊曲康唑和酮康唑的保留时间分别为 1.12、1.09、1.09、1.15 和 1.94 min。周期时间为 3 分钟，进样到进样。分析物通过串联质谱仪进行监测。采用正离子模式的选择反应监测（SRM）进行定量。
该方法的检测限为 2-10 ng/mL，定量下限为 14 ng/mL，不同分析物的线性度≥0.999。日内和日间变异系数均<8.1%和<9.8%。准确度范围为 85%至 106%。
验证并成功应用于抗真菌治疗患者样本的 HPLC-MS/MS 法，可快速、灵敏、稳健地定量人血浆中的氟康唑、伊曲康唑、泊沙康唑和伏立康唑水平。
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