To establish an UPLC-MS method for the analysis of salidroside, methyloleoside, specnuezhenide, acteoside, oleuropein, and G13 in plasma, and the differences in pharmacokinetic profiles of five different concoctions of Ligustri Lucidi Fructus, wine Ligustri Lucidi Fructus, vinegar Ligustri Lucidi Fructus, salt Ligustri Lucidi Fructus and steamed Ligustri Lucidi Fructus in vivo of rats were investigated.

SPF-grade male SD rats were randomly divided into 6 groups, and were given 4.2 g·kg^-1 of aqueous extracts of different concoctions of Ligustri Lucidi Fructus by gavage (for the amount of raw drug), and the plasma samples were methanol-precipitated proteins with geniposide as the internal standard, and the plasma samples were used to determine salidroside, methyloleoside, specnuezhenide, acteoside, oleuropein, and G13 in the plasma of the rats in the different time points by using the negative-ion SIM mode of UPLC-MS/MS. Kinetica 5.1 software was used to calculate the pharmacokinetic parameters, and GraphPad Prism 8.4.0 software was used to analyze the data.

The mass concentrations of salidroside, methyloleoside, specnuezhenide, acteoside and oleuropein were in the range of 2.00-1 385 ng·mL^-1, and the mass concentration of G13 was in the range of 1.30-650 ng·mL^-1, with good linearity, the relative standard deviations of the precision were all less than 10%, the recoveries of the extracts were all in the range of 85%-105%, and the matrix effect and stability were in accordance with the requirements of biological samples. The results of pharmacokinetic study showed that the AUC_0-∞, MRT_0-t, t_1/2, and C_max of acteoside were significantly higher in wine Ligustri Lucidi Fructus (P<0.01) compared to raw Ligustri Lucidi Fructus, which was 751.36 ng·mL^-1·h, 5.87 h, 377.82 h, and 38.11 ng·mL^-1, respectively. C_max, AUC_0-∞, and t_1/2 were significantly higher (P<0.01) for specnuezhenide and G13 in salt Ligustri Lucidi Fructus compared to raw Ligustri Lucidi Fructus, with C_max of specnuezhenide and G13 in salt Ligustri Lucidi Fructus were 66.45 ng·mL^-1 and 204.27 ng·mL^-1, respectively. The AUC_0-∞ were 342.69 ng·mL^-1 and 423.44 ng·mL^-1·h, and t_1/2 were 101.64 h and 15.98 h, respectively. Compared to raw Ligustri Lucidi Fructus, the C_max of oleuropein was significantly higher (P<0.05) in vinegar Ligustri Lucidi Fructus, wine Ligustri Lucidi Fructus, and steamed Ligustri Lucidi Fructus with 66.81 ng·mL^-1, 68.00 ng·mL^-1, and 66.38 ng·mL^-1, respectively. The AUC_0-∞ of salidroside and methyloleoside was the highest in vinegar Ligustri Lucidi Fructus, which was 5 782.74 ng·mL^-1 and 545.26 ng·mL^-1·h, respectively.

This study reveals the changing law of the six active ingredients in different artillery products of Ligustri Lucidi Fructus in vivo and their different characteristics, which provides a basis for the clinical application of different artillery products of Ligustri Lucidi Fructus.