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Drug Res (Stuttg) 2013; 63(12): 644-649
DOI: 10.1055/s-0033-1358665
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

A Validated Method for Quantifying Entecavir in Biological Matrices and Its Application in a Pharmacokinetic Study in Rats and Dogs

X. Huang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
2   Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, P. R. China
,
Z.-Z. Jiang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
W.-W. Tang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Y. Xiao
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
L.-Y. Zhang
1   Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Z.-J. Zhang
2   Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, P. R. China
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Publikationsverlauf

received 02. Mai 2013

accepted 05. Oktober 2013

Publikationsdatum:
07. November 2013 (online)

Auch verfügbar auf
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Abstract

A sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method that uses ganciclovir as an internal standard (IS) has been developed and validated for quantifying entecavir in rat and dog plasma. Following solid-phase extraction (SPE), the analytes were separated on an Inertsil® ODS-3 (5 μm, 150 mm×2.1 mm i.d.) column and analyzed in selected ion monitoring (SIM) mode with a positive electrospray ionization (ESI) source using the [M+H]+ ions, 278.1 for entecavir and 256.0 for ganciclovir. The method was validated over the concentration range of 0.01–9 μg/mL for entecavir. All precisions (RSD) within and between batches were less than 10%, and accuracies ranged from 98.1 to 102.5%. The lower limit of quantification was 0.01 µg/mL. The extraction recovery averaged 93.9–96.7%. The validated method was used for a pharmacokinetic study of entecavir in rats and dogs. The following pharmacokinetic parameters were obtained for rats and dogs, respectively: the area under the plasma concentration vs. time curves from time 0 to 24 h (AUC0–24) were 15.4±4.5 and 23.4±7.2 μg∙h/mL; the mean maximum plasma concentration (Cmax) were 2.4±0.8 and 5.0±0.9 μg/mL; the mean time to reach the maximum plasma concentrations (Tmax) were 1.7±0.7 and 1.5±0.4 h; and the mean elimination half-life (t1/2) were 5.3±1.4 and 3.8±1.3 h.

Key words

entecavir - pharmacokinetics - LC/MS - rat - dog
 

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