Background: TJAB1099 is a novel, highly active inhibitor of human enterovirus 71
(HEV71), which is a most commonly found virus leading to Hand-Foot-Mouth Disease (HFMD). However,
the TJAB1099 could not be detected in the plasma using a regular HPLC-UV detection during the
pharmacokinetic study due to the poor solubility, which in turn limited the release prior to be absorbed
by the gastrointestinal tract.
Objective: The objectives of the present study were to improve the solubility by preparing formulation
and develop an Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLCMS/
MS) method applied to the pharmacokinetic study.
Method: The TJAB1099 was prepared as a phospholipid complex that intends to increase the watersolubility
and subsequently improving TJAB1099 exposed in the circulation system. A highly sensitive
UPLC-MS/MS method was developed for the pharmacokinetic study, in which the pharmacokinetic
parameters were determined following oral and intravenous administration of 5 mg/kg and 1 mg/kg of
TJAB1099 in rats, respectively.
Results: The precisions for the method were less than 12.8%, while the accuracies were in the range of
90.8 - 98.0% and 96.1 - 99.6% for within-day and between-day, respectively. The mean recoveries for
TJAB1099 and terfenadine (internal-standard, IS) were 85.0 ± 5.4% and 92.4 ± 4.1%, respectively. The
pharmacokinetic study revealed that the Cmax of TJAB1099 after oral administration can reach 6.84 ±
2.43 ng/mL, while the Tmax is 0.70 ± 0.11 h. The AUC0-12 is 19.81 ± 11.07 µg/mL/h. However, the absorption
was poor with an absolute oral bioavailability of 0.62.
Conclusion: The UPLC-MS/MS method was successfully applied in the pharmacokinetic study of
TJAB1099 in rats.
Keywords: Hand-foot-and-mouth disease, UPLC-MS/MS, pharmacokinetics, bioavailability, enterovirus 71, phospholipid complex
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