Objective      To study the

in vivo

release of methotrexate (MTX) from luteinizing hormone- releasing hormone (LHRH) modified MTX in model animals.       Methods      A total of 60 nude BALB/c mice received a subcutaneous injection of MCF-7 cells

and 50 of them with tumor mass in size of 1.5 cm served as model animals. These mice were further divided into 2 groups

and received an injection of 10 mg/kg MTX and 28 mg/kg LHRH-MTX respectively by tail vein. Then the animals were killed at 1

2

4

12 and 24 h after injection (5 mice at each time points)

and their blood and heart

liver

spleen

kidney and tumor mass were collec

ted. A HPLC method was established to determine the concentrations of drugs in the plasma and other tissues of the tumor-bearing nude mice. Compared with MTX injection

the capacity of the

in vivo

release of MTX from LHRH-MTX was evaluated.       Results      The recoveries of our established HPLC method were more than 85%

and the relative standard deviations of the intra-day and inter-day were lesser than 10%. After venous administration

the concentrations of MTX from LHRH-MTX group were higher in tumor tissues（

P

<

0.05）

but lower in the plasma

liver and kidney（

P

<

0.05）.       Conclusion      Our established HPLC method is easy to determine the

in vivo

release of LHRH-MTX. LHRH-MTX significantly changes the distribution of MTX

in vi

vo and evidently increases the concentrations of MTX in the tumor tissues.