| Antitumor Drug CG007 is a kind of PARP-1 inhibitors which now are very popular. The vivo and pharmacodynamics study shows that CG007 has antitumor effect. It can prolong the survival time of tumor-bearing animals.The mechanism of CG007 is that PARP-1 in tumor cells is much more than normal cells, we can use PARP-1 inhibitors to reduce tumor cells' DAN repair fuction and enhance the sensitivity of cancer cells to DNA damage factors, so as to improve the effect of chemotherapy and radiotherapy.The paper mainly studied how to estabilish the method of CG007 biopharmarmaeeutical analysis, and researched the conditions of the drug's absorption and tisstue distribution in mice, in order to provide reference data for further study. Some conclusions were taken in the below:(1) Established a method for determination of CG007. CG007 was determined by a reversed phase high performance liquid chromatography method. CG007 could be quantitatively determined under such chromatographic conditions:Krosmail-C18 column (4.6 mm×250 mm,5μm), and mobile phase:methanol-deionized water, containing 0.1% TFA, (60:40,v:v).with a flow rate of 1.0 mL·min-1, and detection wavelength is 276nm, the column temperature was 20℃.(2) Established a method for determination of CG007 in biological smples. In the preprocess, we used methanol as plasma deproteination reagent, acidified methanl as tissue deproteination reagent. This method had good effect, recovery was between 95.33%-110.96%, intra-day RSD was less than 5.92%, inter-day RSD was less than 6.59%, and there was no interference of endogenous substances. The chromatographic conditions were the same to the determinantion of CG007.(3) Studied the vivo absorption kinetics and tissue distribution of drug CG007 in mice. Detection method was the same to the determination of CG007 in biological smple.In the absorption kinetics experiments, injection and oral administrations were given to the mice, and the administration dose was respectively 10,20,30mg·kg-1. After injection administration, t1/2α/h was respectively 0.031±0.002,0.163±0.021,0.079±0.003, t1/2β/h was respectively 0.498±0.015,1.950±0.543,3.027±1.032, AUC(0-∞)/ng·ml-1·h-1 is respectively 6003.394±678.432,13651.617±2830.345,21928.17±4213.246. After oral administration,t1/2α/h i was respectively 1.126±0.298,1.279±0.135,2.075±0.458, t1/2β/h was respectively 1.128±0.056,1.283±0.034,3.873±1.232, AUC(0-∞)/ng·ml-1·h-1 was respectively 3132.049± 560.322,6860.27±239.065,16128.6927±4309.453,5535.055±789.436,10133.45±2321.734. The results showed that the pharmacokinetics of CG007 in mice plasma agreed with two-compartment model. CG007 was dose-independent over the range of 250-2500 ng·ml-1 in mice. After i.v.administration of 10mg·kg-1, the absolute bioavaiabilty of antitumor drug CG007 was 51.17%.The distribution study of CG007 in mice showed that CG007 could be extensively distributed, After i.v administration with 10mg·kg-1, we found the highest concentration in kidney, liver was less and the concentration in heart, brain, lung was similar to each other. |
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