Abstract:
A method is established for determining the concentration of AP121, a new anti-depressant, in the main organs and tissues of rats, to study on its distribution, and to explore the target organs of AP121. 24 healthy SPF SD rats were randomly divided into three groups: A, B and C, with 8 rats in each group, half male and half female. One rat in each group was randomly selected as the blank control group (0 h), the other 7 rats were given AP121 Labrasol solution at 19.32 mg·kg
−1, then the tissue samples of heart, liver, spleen, lung and kidney were collected at 1 h, 4 h and 9 h. The AP121 in 5 viscera tissues were detected by HPLC-MS/MS. As results, the concentration distribution of AP121 in five tissues at 1 h, 4 h and 9 h was as follows: liver > lung > heart > spleen > kidney, lung > liver > heart > spleen > kidney, liver > lung > heart > spleen > kidney; the individual difference of AP121 in lung, heart and liver was great; AP121 in liver reached the highest concentration at 1 h, and AP121 in other 4 organs reached the highest concentration at 4 h. At 9 h, the concentration in all tissues decreased significantly and was lower than at 1 h. The analysis results show that the LC-MS/MS method for the determination of AP121 in 5 main organs of rats is sensitive, accurate and reliable, which can provide technical support for the pharmacokinetic evaluation of AP121. Liver and lung may be the target organs of AP121. In the subsequent drug development process, attention should be paid to the individual effects of drugs on lung, heart and liver, and the difference should be serious in the effects of drugs on the liver and lungs.