Prommas Santirat, Puangpetch Apichaya, Jenjirattithigarn Nuttawut, Chuwongwattana Sumonrat, Jantararoungtong Thawinee, Koomdee Napatrupron, Santon Siwalee, Chamnanphon Montri, Sukasem Chonlaphat
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
J Clin Lab Anal. 2017 Jan;31(1). doi: 10.1002/jcla.22011. Epub 2016 Jun 24.
Voriconazole (VRZ) is a triazole antifungal used for treatment of invasive fungal infection, which is a life-threatening condition. Therapeutic drug monitoring is recommended for identifying the optimal dose in patients who have hepatic/renal impairment or reduced function of the CYP2C19 metabolizing enzyme.
One hundred microliters of sample plasma was extracted by protein precipitated with 200 μl of acetonitrile containing fluconazole as internal standard (IS). After vortexing and centrifugation, supernatant was dried and reconstituted with 100 μl of mobile phase (ACN: 0.1% formic acid in 10 mM Ammonium acetate) (50:50 v/v) before injected. The column was C18, 2.7 μm, 3.0 × 50 mm at flow rate of 0.5 ml/min with retention time of 0.5 and 0.75 min for VRZ and IS, respectively. The tandem mass spectrometer was set in multiple reactions monitoring (MRM) mode with the following transition; VRZ m/z 350.10→281.10 and 307.20→220.20 (IS).
The accuracy and precision inter- and intra-day were less than 9%, over the range 0.05-10 μg/ml. The linearity was consistent (r = 0.9987) and recovery was more than 85.0% for both analyses.
This method is applicable for routine monitoring of patients' VRZ plasma level with fast and accurate runtime to assess CYP2C19 genotype.
伏立康唑（VRZ）是一种用于治疗侵袭性真菌感染的三唑类抗真菌药物，侵袭性真菌感染是一种危及生命的疾病。对于肝/肾功能受损或CYP2C19代谢酶功能降低的患者，建议进行治疗药物监测以确定最佳剂量。
取100微升样本血浆，用含氟康唑作为内标（IS）的200微升乙腈进行蛋白沉淀提取。涡旋和离心后，将上清液干燥，并用100微升流动相（乙腈：10 mM醋酸铵中的0.1%甲酸）（50:50 v/v）复溶后进样。色谱柱为C18，2.7μm，3.0×50 mm，流速为0.5 ml/min，伏立康唑和内标的保留时间分别为0.5分钟和0.75分钟。串联质谱仪设置为多反应监测（MRM）模式，有以下跃迁；伏立康唑m/z 350.10→281.10和307.20→220.20（内标）。
在0.05 - 10μg/ml范围内，日内和日间的准确度和精密度均小于9%。两种分析的线性均良好（r = 0.9987），回收率均超过85.0%。
该方法适用于常规监测患者的伏立康唑血浆水平，运行时间快速准确，可用于评估CYP2C19基因型。
