A sensitive UHPLC–MS/MS method for the simultaneous quantification of three lignans in human plasma and its application to a pharmacokinetic study

Abstract

The aim of this study was to develop an analytical method to simultaneously analyze schizandrin, schizandrol B, and gomisin N lignans in human plasma using ultra high performance liquid chromatography with tandem mass spectrometry. The three lignans were separated using a mobile phase of water and acetonitrile containing 0.02% acetic acid equipped with a Kinetex C column (2.1 mm × 50 mm, 1.7 μm). This analysis was achieved by multiple reaction monitoring mode in an electrospray interface. The mass transitions were m/z 433.1→384.0 for schizandrin, 398.8→367.8 for schizandrol B, and 400.6→299.8 for gomisin N. Liquid-liquid extraction with methyl tert-butyl ether was used to obtain the three lignans. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma constituents. The calibration curves for the three lignans in human plasma were 0.05-50 ng/mL and displayed excellent linearity with correlation coefficients greater than 0.99. Precision for all three lignans was within 11.23%. The accuracy was 88.3-99.0% for schizandrin, 90.6-103.4% for schizandrol B, and 90.2-103.5% for gomisin N. The developed simultaneous analytical method satisfied the criteria of international guidance and could be successfully applied to the pharmacokinetic study of three lignans after oral administration of Schisandrae Fructus extract powder to humans.

A Rapid UPLC-MS Method for Quantification of Gomisin D in Rat Plasma and Its Application to a Pharmacokinetic and Bioavailability Study

“…× 100%, suggesting that gomisin D may become a promising intragastrical medication. In fact, most lignan compounds show a higher absorption or bioavailability, such as gomisin J [2,27,28]. Gomisin D shows better absorption than other lignans [19].…”

Potential for pharmacokinetic interactions between Schisandra sphenanthera and bosutinib, but not imatinib: in vitro metabolism study combined with a physiologically‐based pharmacokinetic modelling approach

“…This was necessary because concentration of schisandrol B in S. sphenanthera extract used in the former was questionably far lower than that normally found in commercially available extracts (0.01 55 vs 0.05–0.07% 56,61 ). This resulted in unrealistically high and low values of AUC and the corresponding apparent clearance ( CL/F ) of schisandrol B, respectively 55 and thus, clinical pharmacokinetic data from the study by Kim et al 56 was used instead to verify the PBPK model of schisandrol B. Unfortunately, clinical data of both schisandrin A and schisantherin A were not reported in this study.…”

“…It is noteworthy that while clinical pharmacokinetic data for schisandrin A and schisantherin A were extracted from a study by Wei et al 55 clinical data of schisandrol B were taken from another study 56 . This was necessary because concentration of schisandrol B in S. sphenanthera extract used in the former was questionably far lower than that normally found in commercially available extracts (0.01 55 vs 0.05–0.07% 56,61 ).…”

“…It is noteworthy that while clinical pharmacokinetic data for schisandrin A and schisantherin A were extracted from a study by Wei et al 55 clinical data of schisandrol B were taken from another study 56 . This was necessary because concentration of schisandrol B in S. sphenanthera extract used in the former was questionably far lower than that normally found in commercially available extracts (0.01 55 vs 0.05–0.07% 56,61 ). This resulted in unrealistically high and low values of AUC and the corresponding apparent clearance ( CL/F ) of schisandrol B, respectively 55 and thus, clinical pharmacokinetic data from the study by Kim et al 56 was used instead to verify the PBPK model of schisandrol B.…”