Simultaneous Quantification of Gallic Acid, Bergenin, Epicatechin, Epicatechin Gallate, Isoquercitrin, and Quercetin-3-Rhamnoside in Rat Plasma by LC-MS/MS Method and Its Application to Pharmacokinetics after Oral Administration of Ardisia japonica Extract

Ardisia japonica is a well-known traditional Chinese medicinal herb used as a diuretic, for treating cough and for stopping uterine bleeding. A simple, sensitive, and reliable LC-MS/MS method was developed to determine six active compounds in rat plasma and this method was further applied to the pharmacokinetic study of these compounds after oral administration of Ardisia japonica extract. Acetonitrile was used to precipitate the protein in the plasma samples. Using acetonitrile and formic acid aqueous solution (0.05%) as themobile phase, the separation of the six compounds and internal standards was achieved at a flow rate of 300 mu L min(-1) on an Eclipse plus C-18 column at an elution time of 16 min. A tandem mass spectrometer having an electrospray ionization (ESI) source was used in the detection of the analytes and internal standards using multiple reactions monitoring (MRM) in the negative ionization mode. The LLOQ was 2, 2, 4, 2, 1, and 0.4 ng mL(-1) for gallic acid, bergenin, epicatechin, epicatechin gallate, isoquercitrin, and quercetin-3-rhamnoside, respectively. The validated method was applied to the pharmacokinetic study of gallic acid, bergenin, and quercetin-3-rhamnoside in rat plasma after oral administration of A. japonica extract to rats.