Preclinical pharmacokinetic investigation of the bioavailability and skin distribution of HY-072808 ointment, a novel drug candidate for the treatment of atopic dermatitis, in minipigs by a newly LC-MS/MS method.

HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC-MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1-7.6% after transdermal application of 1-4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug.

Preliminary study on the association between lignan metabolites and CT non-destructive testing of coconut fruit at different developmental stages.

Lignans play a crucial role in maintaining plant growth, development, metabolism and stress resistance. Computed tomography (CT) imaging technology can be used to explore the internal structure and morphology of plants, and understanding the correlation between the two is highly significant. In this study, the content of lignan metabolites in coconut water was determined using liquid chromatography. The internal structure data of coconut fruit was obtained by CT scanning, and the relationship between lignan metabolites and CT image data at different developmental stages was evaluated using partial least square (PLS) regression. The results showed that the total lignan content in coconut water initially decreased, then increased, and gradually decreased after the maturity stage. The Wenye No. 5 variety exhibited higher levels of Epiturinol, Turbinol, Isobarinin-9'-o-glucoside, 5'-methoxy-rohanoside, Rohan rosin-4,4'-di-o-glucoside, turbinol-4-O-glucoside, cycloisoperinolin-4-O-glucoside compared to local coconuts. Coconut meat had the greatest effect on Rohan rosin-4,4'-di-o-glucoside, coconut water on Daphne, and coconut shell and coconut fiber on Larinin-4'-o-glucoside. The data from different parts of coconut fruit's images showed a significant correlation with the content of lignan metabolites. This study has preliminarily explored the correlation between non-destructive testing of coconut fruit and its development process of coconut fruit, providing a new approach and method for further research on non-destructive testing of coconut fruit development.