Simultaneous determination of acyclovir, ganciclovir, and (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine in human plasma using high-performance liquid chromatography.
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 microL), 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.
Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN, USA.
Dennis R
DR
Weller
Henry H
HH
Balfour
Heather E
HE
Vezina
D000212:Acyclovir / Q000097:blood* / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000097:blood* / Q000493:pharmacokinetics; D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods*; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy; D015774:Ganciclovir / Q000097:blood* / Q000493:pharmacokinetics; D006147:Guanine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004854:Herpesvirus 4, Human / Q000187:drug effects; D006801:Humans; D016030:Kidney Transplantation; D018401:Sample Size; D012680:Sensitivity and Specificity; D013997:Time Factors; D055815:Young Adult
D000998:Antiviral Agents; C051755:9-(4-hydroxy-2-(hydroxymethyl)butyl)guanine; D006147:Guanine; D015774:Ganciclovir; D000212:Acyclovir