A new sample preparation method for the determination of acyclovir by RP-HPLC: application to a drug-drug interaction study between gefitinib and acyclovir in rats

doi:10.5246/jcps.2021.06.038

Abstract

Abstract:

The assay of acyclovir in plasma seems to be a challenge because of its high hydrophily. In our present study, a reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of acyclovir in rat plasma was described and validated in drug-drug interaction (DDI) between gefitinib and acyclovir in rats. The analytes were separated with gradient elution on C₁₈ column (4.6 mm × 250 mm, 5 μm), and the peaks were recorded using ultraviolet detector at a wavelength of 254 nm. Protein precipitation followed by methyl tertiary butyl ether extraction was used for sample preparation. The calibration curve was established between 0.2 and 40 μg/mL (r² = 0.9999). The intra- and inter-day precisions were all less than 8%, and all the biases were not more than 10%. This new method was successfully applied to a DDI study between gefitinib and acyclovir in rats. Gefitinib up-regulated the absorption of acyclovir by about three times, and our findings guided the clinical co-administration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with acyclovir.

Key words: Acyclovir, High-performance liquid chromatography, Sample preparation, Absorption, Drug-drug interaction

Supporting:

Ying Li, Zhou Wen, Yongling Liu, Zhibing Zhao, Lei Wang, Zeneng Cheng. A new sample preparation method for the determination of acyclovir by RP-HPLC: application to a drug-drug interaction study between gefitinib and acyclovir in rats[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(6): 495-504.

Figures/Tables 6

Table 1. Intra- and inter-day accuracy and precision of acyclovir in rat plasma.

Table 2. Stability of acyclovir in rat plasma under various conditions (n = 3).

Table 3. The pharmacokinetic parameters of acyclovir with and without the co-administration of gefitinib (n = 6).

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