A Simple High-performance Liquid Chromatographic Method for the Determination of Acyclovir in Human Plasma and Application to a Pharmacokinetic Study

Abstract

A rapid, simple and sensitive reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the measurement of acyclovir (CAS 59277-89-3) concentrations in human plasma and its use in bioavailability studies is evaluated. The method was linear in the concentration range of 0.05–4.0 µg/ml. The lower limit of quantification (LLOQ) was 0.05 µg/ml in 0.5 ml plasma sample. The intra- and inter-day relative standard deviations across three validation runs over the entire concentration range were less than 8.2 %. This method was successfully applied for the evaluation of pharmacokinetic profiles of acyclovir capsule in 19 healthy volunteers. The main pharmacokinetic parameters obtained were: AUC_0-t 6.50 ± 1.47 and 7.13 ± 1.44 µg . h/ml, AUC_0-∞ 6.77 ± 1.48 and 7.41 ± 1.49 µg . h/ml, C_max 2.27 ± 0.57 and 2.27 ± 0.62 µg/ml, t_1/2 2.96 ± 0.41 and 2.88 ± 0.33h, t_max 0.8 ± 0.3 and 1.0 ± 0.5 h for test and reference formulations, respectively. No statistical differences were observed for C_max and the area under the plasma concentration – time curve for acyclovir. 90 % confidence limits calculated for C_max and AUC from zero to infinity (AUC_0-∞) of acyclovir were included in the bioequivalence range (0.8–1.25 for AUC).

Key words

Acyclovir, bioavailability, chromatography, pharmacokinetics - Antiviral agents - CAS 59277-89-3

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