Several drugs are administered to lung‐transplanted patients, which are monitored using therapeutic drug monitoring (TDM). Therefore, we developed and validated a liquid chromatography–tandem mass spectrometry method to simultaneously analyze immunosuppressive drugs such as mycophenolic acid, antifungal drugs such as voriconazole and itraconazole, and its metabolite hydroxyitraconazole. Chromatographic separation was achieved using a C18 column and gradient flow of mobile phase comprising 20 mM aqueous ammonium formate and 20 mM ammonium formate‐methanol solution. A simple protein precipitation treatment was performed using acetonitrile/methanol and mycophenolic acid‐²H₃, voriconazole‐²H₃, itraconazole‐²H₄, and hydroxyitraconazole‐²H₄ as internal standards. The linearity ranges of mycophenolic acid, voriconazole, itraconazole, and hydroxyitraconazole were 100–20,000, 50–10,000, 5–1000, and 5–1000 ng/mL, respectively. The retention time of each target was less than 2 min. The relative errors in intra‐ and inter‐day were within ±7.6%, the coefficient of variation was 8.9% or less for quality control low, medium, and high, and it was 15.8% or less for lower limit of quantitation. Moreover, the patient samples were successfully quantified, and they were within the linear range of measurements. Therefore, our new method may be useful for TDM in lung‐transplanted patients.

中文翻译：

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使用液相色谱-串联质谱法同时分析向肺移植患者给药的药物，以监测治疗药物

肺移植患者服用了几种药物，并使用治疗药物监测（TDM）进行监测。因此，我们开发并验证了液相色谱-串联质谱方法，用于同时分析免疫抑制药物（例如麦考酚酸），抗真菌药物（例如伏立康唑和伊曲康唑）及其代谢产物羟基伊曲康唑。使用C18色谱柱和包含20 mM甲酸铵水溶液和20 mM甲酸铵-甲醇溶液的流动相进行梯度流色谱分离。使用乙腈/甲醇和霉酚酸² H ₃，伏立康唑² H ₃，伊曲康唑² H进行简单的蛋白质沉淀处理₄和羟基依他康唑² H ₄作为内标。霉酚酸，伏立康唑，伊曲康唑和羟基伊曲康唑的线性范围分别为100–20,000、50–10,000、5–1000和5–1000 ng / mL。每个靶标的保留时间少于2分钟。日内和日间的相对误差在±7.6％内，对于质量控制的低，中和高水平，变异系数为8.9％以下，而定量下限为15.8％以下。此外，患者样品已成功定量，并且在测量的线性范围内。因此，我们的新方法可能对肺移植患者的TDM有用。