Department of Pharmacy, Peking University Third Hospital, Beijing, PR China.
Clin Chem Lab Med. 2013 Feb;51(2):339-46. doi: 10.1515/cclm-2012-0364.
Voriconazole and itraconazole are two broad-spectrum antifungal triazole derivates administered for the prevention and in the treatment of invasive fungal infections. Their broad inter- and intra-individual pharmacokinetic variability and the high probability of drug-drug interactions justify therapeutic drug monitoring.
After liquid-liquid extraction with tert-butyl methyl ether, chromatographic separation was achieved on a Zorbax Eclipse XDB-C18 column using gradient elution with 10 mM ammonium formate and acetonitrile. Detection was performed by a tandem mass spectrometer coupled to LC via an atmospheric pressure chemical ionization (APCI) and quantification was performed using selected reaction monitoring (SRM) transitions
Total run time was 4.5 min. The method was validated for concentrations ranging from 0.05 to 10 μg/mL for voriconazole and from 0.025 to 5 μg/mL for itraconazole and hydroxyitraconazole, respectively. The intra- and inter-day correlation coefficients of variation were <7.7%-<9.2%, respectively. The accuracy ranged from 92.6% to 109%.
A rapid and simple liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (LC-APCI-MS/MS) method has been developed and validated to measure voriconazole itraconazole and hydroxyitraconazole in human plasma. This method is successfully applied to samples from patients receiving antifungal treatment.
伏立康唑和伊曲康唑是两种广谱抗真菌三唑衍生物，用于预防和治疗侵袭性真菌感染。它们广泛的个体间和个体内药代动力学变异性以及高药物相互作用的可能性证明了治疗药物监测的合理性。
经过叔丁基甲基醚液液萃取后，采用 10 mM 甲酸铵和乙腈梯度洗脱，在 Zorbax Eclipse XDB-C18 柱上进行色谱分离。通过大气压化学电离（APCI）将 LC 与串联质谱仪耦合进行检测，并通过选择反应监测（SRM）跃迁进行定量。
总运行时间为 4.5 分钟。该方法针对伏立康唑的浓度范围为 0.05 至 10 μg/mL，伊曲康唑和羟基伊曲康唑的浓度范围分别为 0.025 至 5 μg/mL 进行了验证。日内和日间变异系数均<7.7%-<9.2%。准确度范围为 92.6%至 109%。
已经开发并验证了一种快速简单的液相色谱-大气压化学电离-串联质谱（LC-APCI-MS/MS）方法，用于测量人血浆中的伏立康唑、伊曲康唑和羟基伊曲康唑。该方法成功应用于接受抗真菌治疗的患者样本。
