Development and Validation of Voriconazole Concentration by LC-MS-MS: Applied in Clinical Implementation

被引:17
作者
Prommas, Santirat [1 ,2 ]
Puangpetch, Apichaya [1 ,2 ]
Jenjirattithigarn, Nuttawut [1 ,2 ]
Chuwongwattana, Sumonrat [1 ,2 ]
Jantararoungtong, Thawinee [1 ,2 ]
Koomdee, Napatrupron [1 ,2 ]
Santon, Siwalee [1 ,2 ]
Chamnanphon, Montri [1 ,2 ]
Sukasem, Chonlaphat [1 ,2 ]
机构
[1] Mahidol Univ, Fac Med, Ramathibodi Hosp, Div Pharmacogen & Personalized Med,Dept Pathol, Bangkok, Thailand
[2] Ramathibodi Hosp, Somdech Phra Debaratana Med Ctr SDMC, Lab Pharmacogen, Bangkok, Thailand
关键词
antifungal; applications; genetics; LC-MS/MS; quantitative; PERFORMANCE LIQUID-CHROMATOGRAPHY; HUMAN PLASMA; PHARMACOKINETICS; SAFETY; ASSAY; SERUM;
D O I
10.1002/jcla.22011
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Background: 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. Methods: One hundred microliters of sample plasma was extracted by protein precipitated with 200 mu l of acetonitrile containing fluconazole as internal standard (IS). After vortexing and centrifugation, supernatant was dried and reconstituted with 100 l 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 m, 3.0 x 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). Results: The accuracy and precision inter- and intra-day were less than 9%, over the range 0.05-10 mu g/ml. The linearity was consistent (r(2) = 0.9987) and recovery was more than 85.0% for both analyses. Conclusion: This method is applicable for routine monitoring of patients' VRZ plasma level with fast and accurate runtime to assess CYP2C19 genotype. (C) 2016 Wiley Periodicals, Inc.
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页数:7
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