Imidol hydrochloride is a novel agent for the treatment of hepatitis B virus (HBV) infection, which is currently being evaluated in a phase II trial. This study investigated the absorption, excretion and tissue distribution of imidol after an oral dose in rats. The pharmacokinetic parameters were determined for both intravenous and oral dosing. A simple and sensitive UPLC-MS-MS method was employed to determine the imidol levels in rat biological samples. It was applied for the analysis of imidol in plasma, urine, feces, bile and various tissue samples. Imidol was found to have a moderate half-life (∼4 h), a relatively large apparent distribution volume and rapid clearance after an IV dose and oral doses up to 70 mg kg(-1). Dose-dependent linear relationships of AUC0-t and Cmax for imidol was found in the range of 10-70 mg kg(-1) after oral administration to rats. However, the oral bioavailability was low (17.6%). Most of the drug was metabolized and only 20% of the parent drug was excreted. Imidol excreted mainly in feces. The tissue distribution results show that imidol was quickly dispersed to various tissues following an oral dose. Relatively high concentration was found in liver, which is beneficial to the intended indication. Very low levels of imidol were found in brain and testes, indicating that it was difficult for imidol to cross the blood-brain barrier.

2012-04-01·Biomedical chromatography : BMC4区 · 医学

Determination of imidol hydrochloride in human plasma and urine by high‐performance liquid chromatography–tandem mass spectrometry and its application to clinical pharmacokinetic study

4区 · 医学

Article

作者: Bi, Kaishun ; Gong, Ping ; Hu, Xin ; Chen, Xiaohui ; Li, Yang ; Li, Kexin ; Shi, Zhengyuan

ABSTRACT:

Imidol hydrochloride is a novel drug for the treatment of hepatitis B virus infection. A simple, special and sensitive solid‐phase extraction liquid chromatography–tandem mass spectrometry method for determination of imidol in human plasma and urine was developed for the first time and applied to a pharmacokinetic study. The chromatographic separation was achieved on a C18 column (50 × 2.1 mm, 3.5 µm) using gradient elution with acetonitrile and water both containing 0.1% acetic acid at a flow rate of 0.25 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode via a positive eletrospray ionization source. The mass transition pairs of m/z 517.8 → 325 and m/z 298 → 174 were used to detect imidol and the (−)‐clausenamide (internal standard), respectively. The retention times of imidol and (−)‐clausenamide were 2.5 and 2.7 min, respectively. Linearity, accuracy, precision, recovery, matrix effect, dilution test and stability were evaluated during method validation over the range of 0.2–500 ng/mL in human plasma and 0.5–500 ng/mL in urine. The method was successfully applied to a clinical pharmacokinetic study of imidol in healthy volunteers following oral administration. Copyright © 2011 John Wiley & Sons, Ltd.

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