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Simultaneous determination of acyclovir, ganciclovir, and ( R )‐9‐[4‐hydroxy‐2‐(hydroxymethyl)butyl]guanine in human plasma using high‐performance liquid chromatography
Author(s) -
Weller Dennis R.,
Balfour Henry H.,
Vezina Heather E.
Publication year - 2009
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1192
Subject(s) - chemistry , ganciclovir , guanine , chromatography , hydroxymethyl , pharmacokinetics , in vivo , high performance liquid chromatography , in vitro , protein precipitation , pharmacology , human cytomegalovirus , biochemistry , stereochemistry , medicine , nucleotide , microbiology and biotechnology , biology , gene
Abstract Acyclovir, ganciclovir and ( R )‐9‐[4‐hydroxy‐2‐(hydroxymethyl)butyl]guanine are active in vitro against the Epstein–Barr virus (EBV) but their in vivo anti‐EBV activity is not well understood. We developed a novel, sensitive high‐performance liquid chromatography assay with ultraviolet detection for measuring acyclovir, ganciclovir and ( R )‐9‐[4‐hydroxy‐2‐(hydroxymethyl)butyl]guanine in human plasma to identify quantitative relationships between in vitro anti‐EBV activity and therapeutic response. Characteristics of the assay include a low plasma volume (200 µL), perchloric acid protein precipitation, use of penciclovir as the internal standard, run times less than 8 min and a 50 ng/mL lower limit of quantification. The within‐ and between‐assay variability is 0.7–4.8 and 1.0–7.9%, respectively. Accuracy for all three drugs ranges from 89.5 to 106.4% for four quality controls (50, 100, 1000 and 10,000 ng/mL). This assay supports pharmacokinetic and pharmacodynamic studies of candidate anti‐EBV drugs in children and adults with EBV infections. Copyright © 2009 John Wiley & Sons, Ltd.