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

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.