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LC-ESI-MS/MS Analysis and Pharmacokinetics of GP205, an Innovative Potent Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A Protease in Rats

1,2,†, 1,2,†, 1,2, 1,2,3, 1,2, 1,2, 4 and 1,2,*
School of Pharmacy, Second Military Medical University, Shanghai 200433, China
Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Shanghai 200433, China
Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China
Ginkgo Pharma Co. Ltd., Suzhou 205125, China
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Derek J. McPhee
Molecules 2015, 20(3), 4319-4336;
Received: 7 December 2014 / Revised: 12 February 2015 / Accepted: 25 February 2015 / Published: 6 March 2015
(This article belongs to the Section Medicinal Chemistry)
PDF [1142 KB, uploaded 6 March 2015]


A high-throughput, sensitive and specific LC-ESI-MS/MS method was established for the quantitative determination of GP205, a potent inhibitor of hepatitis C virus NS3/4A protease, in rat. The analyte was isolated from 25 μL plasma sample by 96-well LLE. Good linearity was achieved within the concentration range of 2–5000 ng/mL (r2 > 0.996). The intra- and inter-day precision was less than 10%. The accuracy ranged from 0.8% to 5.5% for GP205 in quality control samples at three levels. GP205 was stable during the analysis and the storage period. The method was successfully applied to pharmacokinetic studies of GP205 in Sprague-Dawley rats. The pharmacokinetic profiles of GP205 at three dose levels with oral administration and one dose level with intravenous administration were successfully studied for the first time in SD rats, respectively. After single oral administration of GP205 at the doses of 2.5, 5, 10 mg/kg, respectively, Cmax and AUC0-τ were proportional to the doses given. The absolute bioavailability was estimated as 34% based on the AUCs of oral administration at the dose of 5 mg/kg and intravenous administration at the dose of 1 mg/kg. The data presented in this study provides useful information for further study for GP205. View Full-Text
Keywords: GP205; LC-ESI-MS/MS; pharmacokinetics; HS3/4A; HCV GP205; LC-ESI-MS/MS; pharmacokinetics; HS3/4A; HCV

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Yang, N.; Sun, Q.; Xu, Z.; Wang, X.; Zhao, X.; Cao, Y.; Chen, L.; Fan, G. LC-ESI-MS/MS Analysis and Pharmacokinetics of GP205, an Innovative Potent Macrocyclic Inhibitor of Hepatitis C Virus NS3/4A Protease in Rats. Molecules 2015, 20, 4319-4336.

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