Validation of an assay for quantifying ganciclovir in dried blood spots

被引：12
作者：
Rower, Joseph E. [1 ]
Nielson, Chris [2 ]
Shi, Kevin [2 ]
Park, Albert H. [2 ]
机构：
[1] Univ Utah, Coll Pharm, Dept Pharmacol & Toxicol, 30 S 2000 E,Rm 3861, Salt Lake City, UT 84112 USA
[2] Univ Utah, Sch Med, Div Otolaryngol Head & Neck Surg, Salt Lake City, UT USA
来源：
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 2020年 / 184卷
关键词：
Ganciclovir; Dried blood spots; LC-MS/MS; Cytomegalovirus; CONGENITAL CYTOMEGALOVIRUS-INFECTION; ORAL VALGANCICLOVIR; HUMAN PLASMA; PHARMACOKINETICS; NEWBORNS;
D O I：
10.1016/j.jpba.2020.113181
中图分类号：
O65 [分析化学];
学科分类号：
070302 ; 081704 ;
摘要：
Valganciclovir (VGC) is an orally available mono-valyl ester pro drug of the nucleoside analog (NA) ganciclovir (GCV) used to treat cytomegalovirus (CMV). Congenital CMV infection in the newborn is associated with progressive sensorineural hearing loss; however, effective CMV therapy with VGC can improve audiologic outcomes. Ongoing studies to demonstrate the effect of VGC in this setting are hampered by a poor understanding of the pharmacology of VGC and GCV in newborns, and the low blood volumes that can be safely collected from this population. We describe a simple method for determining systemic GCV concentrations using dried blood spot (DBS) samples. GCV was extracted from a single 6 mm punch via sonication in methanol, then quantified using liquid chromatography-tandem mass spectrometry. The assay was accurate and precise in the dynamic range of 10-10,000 ng/mL. GCV concentrations determined in DBS agreed well with GCV concentrations observed in serum. The assay was successfully applied to patient samples, and will be used to support pharmacokinetic studies in an ongoing clinical trial of VGC in infants with CMV-mediated hearing loss. (C) 2020 Elsevier B.V. All rights reserved.
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页数：6
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