Development and validation of a simple and rapid UPLC-MS/MS method for loganin and its application in pharmacokinetic...

Cornus officinalis Sieb. et Zucc. is a medicinal and edible homolog in traditional Chinese medicine. Loganin, an iridoid glycoside, is one of the main active components of Cornus officinalis Sieb. et Zucc. Loganin has been demonstrated to improve depression-like behavior and may be a potential antidepressant candidate. However, the pharmacokinetic characteristics and tissue distribution of loganin, especially in the brain region, are still unclear.

This study aims to investigate the pharmacokinetic characteristics and tissue distribution after oral administration of loganin in rats.

A simple, rapid and reproducible UPLC-MS/MS method was developed and validated for the determination of loganin in rat plasma and tissues. The samples were prepared by acetonitrile precipitation with chloramphenicol as internal standard (IS). Loganin was separated by gradient elution on ACQUITY UPLC®BEH C18 (2.1 × 50 mm, 1.7 μm) using multiple reactions monitoring (MRM) mode. Concentration-time data was subjected to pharmacokinetic analysis. The pharmacokinetic parameters of loganin in rat plasma were analyzed by compartment model using DAS 2.0 software.

The established UPLC-MS/MS method was accurate and reliable with a good linearity (R² > 0.99) in the respective concentration range, satisfying the quantitative requirements. This method was successfully used to study the pharmacokinetics and tissue distribution after oral administration of loganin in rats. The peak time (T_max) of oral administration was about 40 min, and the half-life (t_1/2) was about 50 min, indicating that loganin was quickly absorbed and eliminated in rats. Oral bioavailability was 5.50%. The dose correlation results showed that AUC had a poor correlation with dose, while C_max had a good correlation with dose. In tissues, loganin (35 mg/kg) was highly distributed in the stomach, small intestine, kidney, liver and lung. When the dose was 70 mg/kg, loganin had significant distribution in the cortex.

In this study, a simple and sensitive UPLC-MS/MS method was developed and validated for the determination of loganin in rat plasma and tissues. Loganin was absorbed quickly, eliminated quickly, and had low bioavailability. The distribution of loganin in the cortex was higher than that in the hippocampus. We hope that our results can provide a reference for loganin to become a new antidepressant.