Validation of an LC-MS/MS method for simultaneous detection of diverse components of Qinxing Qingre Zhike Granule in rat plasma and its application to pharmacokinetic study after oral administration to rats.

A sensitive and validated method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established to test the plasma concentrations of active ingredients in Qinxing Qingre Zhike Granule, namely geniposide, liquiritin, isoliquiritin, baicalin, wogonoside, baicalein, liquiritigenin, isoliquiritigenin and glycyrrhetinic acid. The analysis was performed on an Ultimate XB-C column at the flow rate of 0.4 mL min in a single run of 18 min. The mobile phase was composed of 0.05% formic acid in water and acetonitrile with gradient elution. Positive and negative scanning and selected multiple reaction monitoring modes were applied for quantization. The proposed method showed good linearity in the given ranges from 0.6800-340.0 to 3.920-1960 ng mL with r  > 0.9917 for all the analytes. The precision (RSD) was no more than 12%, and the accuracy (RE) was less than ±11% for intra- and inter-day. The extract recovery and matrix effect were acceptable for the requirements of biological sample analysis. Moreover, the developed method was effectively applied to the pharmacokinetic investigation of Qinxing Qingre Zhike Granule after oral administration in rats.