HPLC-MS/MS法测定抗抑郁新药阿姆西汀在大鼠体内的组织分布  

Determination of a Novel Antidepressant Drug by LC-MS /MS and its Distribution in Rat Tissues

作　　者：朱秀清[1] 李敬来[1] 邓鸣[1,2] 熊山[1,3] 张振清[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]解放军261医院,北京100094 [3]浙江中医药大学,浙江杭州310053

出　　处：《解放军药学学报》2014年第1期14-17,共4页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：科技部"重大新药创制"科技重大专项;No.2012ZX09301003-001-007;国家新药创制重大专项课题;No.2012ZX0912110-018

摘　　要：目的研究抗抑郁新药阿姆西汀(S-071031B)在大鼠体内各组织的分布特点。方法雄性SD大鼠随机分组,单剂量(20 mg·kg-1)灌胃给药后,分别于15 min、2、6和24 h处死取血并解剖主要组织,采用LC-MS/MS测定阿姆西汀在生物样品中的药物浓度。结果 SD大鼠灌胃给药15min后即在胃、小肠和肝脏组织中药物浓度达峰值,给药6 h后在睾丸组织中药物浓度达峰值,而在心脏、脾脏、肺脏、肾脏、脑、肌肉组织及血浆均在给药后2 h达到峰值,24 h后各组织中药物浓度均降至较低水平。结论阿姆西汀在大鼠体内吸收迅速,入血后可广泛分布到体内各组织中,药物在体内也快速消除,无组织蓄积作用,具有良好的开发前景。Objective To investigate tissue distribution of S-071031B, a novel antidepressant drug, in rats. Methods 24 male SD rats were randomly divided into 4 groups and were given S-071031B at a dose of 20 mg .kg-1 via o- ral administration. The samples of plasma and main tissues were collected at 15 rain,2 h,6 h and 24 h after administration and a HPLC-MS/MS was developed to determine the concentration of S-071031B in biological samples. Results After po administration of S-071031B at a dose of 20 mg ·kg-1 , the highest S-071031B concentration in male rats was found 15 rain later in the stomach,intestine and liver,6 h later in the testis, and 2 h later in the heart, spleen, lung, kidney, brain, muscle and blood. The tissue concentration of S-071031B decreased to a very low level after 24 h. Conclusion S-071031B can be quickly absorbed, distributed and eliminated after oral administration in rats and no concentration accumulation can be observed in tissues,suggesting that S-071031B has a good prospect of development.

关 键 词：HPLC—MS MS 阿姆西汀 生物样品 组织分布 

分 类 号：R971.43[医药卫生—药品]