Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Department of Pharmaceutical and Environmental Health Sciences, Texas Southern University, Houston, TX, United States.
Clin Chim Acta. 2018 Nov;486:36-41. doi: 10.1016/j.cca.2018.07.022. Epub 2018 Jul 20.
Voriconazole (VOR), an antifungal agent, is clinically monitored to guide therapeutic dosing and avoid toxicity. It is believed that measurement of serum unbound VOR provides more accurate information, especially in hypoalbuminemia patients. We developed and validated an accurate, simple and fast test with ultrafiltration and ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) to measure unbound VOR in human serum.
The Agilent UPLC system coupled with a SCIEX QTRAP4000 MS with a positive ionization mode was developed and validated for VOR analysis.
A good linearity was demonstrated from 0.02 to 2.5 μg/ml for unbound VOR (r = 0.9969). The within-run and between-run accuracy and precision was <5% and < 6%. The levels of total VOR were well correlated with reference laboratory results. Serum unbound VOR levels were correlated with the total VOR levels (r = 0.78, p < 0.0001). There was a reverse correlation between unbound VOR fractions and plasma albumin levels (p < 0.05). In hypoalbuminemia patients, the unbound VOR levels were increased to a higher degree than total VOR.
This assay is suitable for monitoring both unbound and bound VOR in cancer patients especially in those with hypoalbuminemia in clinical laboratories. Measurement of unbound VOR offers a better approach in prediction of VOR toxicity.
伏立康唑（VOR）是一种抗真菌药物，临床上用于指导治疗剂量以避免毒性。人们认为，测量血清中未结合的 VOR 可提供更准确的信息，尤其是在低白蛋白血症患者中。我们开发并验证了一种准确、简单、快速的超滤和超高效液相色谱（UPLC）-串联质谱（MS/MS）检测人血清中未结合 VOR 的方法。
采用安捷伦 UPLC 系统和 SCIEX QTRAP4000 MS/MS 串联质谱系统，正离子模式，建立并验证了 VOR 的分析方法。
未结合 VOR 的线性范围为 0.02-2.5μg/ml（r=0.9969）。批内和批间准确度和精密度均小于 5%和小于 6%。总 VOR 的水平与参考实验室的结果高度相关。血清未结合 VOR 水平与总 VOR 水平相关（r=0.78，p<0.0001）。未结合 VOR 分数与血浆白蛋白水平呈负相关（p<0.05）。在低白蛋白血症患者中，与总 VOR 相比，未结合 VOR 的水平增加得更高。
该检测方法适用于临床实验室中监测癌症患者的游离和结合 VOR，特别是在低白蛋白血症患者中。测量未结合 VOR 可更好地预测 VOR 毒性。
