Validation of an LC-MS/MS Method for Quantitative Analysis of the 5 Bioactive Components of Wuzhi Capsule in Human Plasma Samples

Background: Wuzhi capsule (WZC) is an ethanol extract from the ripe fruit of Schisandra sphenanthera in traditional Chinese medicine that has long been used to treat viral and drug-induced hepatitis in China. The principal active components in WZC are Schisandra lignans. The clinical pharmacokinetics of these components in the form of an oral WZC preparation is unknown. To optimize the WZC dosage and develop WZC-related combination therapies, it is necessary to conduct a comprehensive pharmacokinetic study of the Schisandra lignans.

Methods: A method was developed for simultaneous quantification of multiple bioactive lignans in WZC in human plasma through liquid-liquid extraction followed by multiple reaction monitoring liquid chromatography/tandem mass spectrometry with positive-mode electrospray ionization. The 5 bioactive constituents were separated by isocratic elution using a mobile phase consisting of acetonitrile, methanol, and 0.1% aqueous formic acid at a flow rate of 0.3 mL/min. The total run time was 3.5 minutes.

Results: All analytes showed good linearity over a wide concentration range with a lower limit of quantification at 0.5 ng/mL. Using this method, we determined the 5 bioactive lignans in WZC from human plasma simultaneously and performed a pharmacokinetic study on the Schisandra lignans in healthy volunteers.

Conclusions: Owing to simplicity, quickness, high sensitivity, and selectivity, and a sufficient lower limit of detection of the new liquid chromatography/tandem mass spectrometry method, it may be used as a routine technique for clinical monitoring of WZC, and for understanding interactions between herbal and conventional drug therapies.