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首页> 《中国测试》期刊 >本期导读>肿瘤血管抑制剂DX1002大鼠生物利用度的UPLC-MS/MS法研究

肿瘤血管抑制剂DX1002大鼠生物利用度的UPLC-MS/MS法研究

113    2020-10-27

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作者:钟卓伶1, 王睿1, 雍智全2, 张传维1, 刘书瑶1, 徐小平1

作者单位:1. 四川大学华西药学院,四川 成都 610041;
2. 广州安好医药科技有限公司,广东 广州 510700


关键词:肿瘤血管抑制剂;药代动力学;生物利用度;超高效液相-质谱联用


摘要:

该文建立大鼠血浆中DX1002的浓度的UPLC-MS/MS法,研究DX1002在大鼠体内的药代动力学特性及其生物利用度。DX1002分别经口给药和静脉给药100 mg/kg后,分别于设定的时间点采血,制备出的血浆通过预处理后采用UPLC-MS/MS法测定,色谱条件为UPLC C18为色谱柱(50 mm×2.10 mm,1.7 μm),流量:0.5 mL/min,流动相A相为0.1%甲酸,B相为0.1%甲酸乙腈,采用梯度洗脱;质谱条件为ESI源的MRM检测模式;检测到的血药浓度采用Analyst软件计算药代动力学参数。结果DX1002在1.0~2000 ng/mL内线性良好(r2≥0.9979),精密度、准确度均满足测定需要。口服条件大鼠下平均Cmax分别为35597.0 ng/mL,平均AUC0~24 h为47291.5 h·ng/mL,平均t1/2为2.42 h,平均Tmax为0.235 h;经静脉给药后,雌雄大鼠的平均AUC0~24 h为174043.5 h·ng/mL,平均t1/2为4.26 h。同等剂量下大鼠口服给药的平均绝对生物利用度为27.29%。最后,所建方法是大鼠体内DX1002药代动力学研究的较好方法。


Bioavailability study of tumor vascular inhibitors DX1002 by UPLC-MS/MS in rat
ZHONG Zhuoling1, WANG Rui1, YONG Zhiquan2, ZHANG Chuanwei1, LIU Shuyao1, XU Xiaoping1
1. West China School of Pharmacy, Sichuan University, Chengdu 610041, China;
2. Guangzhou Anhao Pharmaceutical Technology Co., Ltd., Guangzhou 510700, China
Abstract: A UPLC-MS/MS method for the determination of DX1002 in rat plasma was established to study the pharmacokinetics and bioavailability of DX1002 in rat. After oral administration and intravenous administration of DX1002 with 100 mg/kg, blood samples were collected at the set time points. The prepared plasma was determined by UPLC-MS/MS after pretreatment. The chromatographic conditions were ACQUITY UPLC BEH C18 column (50 mm×2.10 mm, 1.7 μm) The flow rate was 0.5 mL/min, the mobile phase a was 0.1% formic acid aqueous solution, the mobile phase B was 0.1% formic acid acetonitrile solution, and the gradient elution was used; the MS condition was the ESI source MRM detection mode; the detected blood concentration was calculated by analyst software. Results the linear range of DX1002 was 1.0-2000 ng/mL (r2≥0.9979). The precision, accuracy, matrix effect and recovery of DX1002 met the needs of determination. The average Cmax, AUC0-24 h, t1/2 and Tmax were 35597.0 ng/mL, 47291.5 h·ng/mL, 2.42 h and 0.235 h, respectively; after intravenous administration, the mean AUC0-24 h and t1/2 of male and female rat were 174043.5 h·ng/mL and 4.26 h, respectively. The average absolute bioavailability was 27.29%. Finally, the established method is a good method to study the pharmacokinetics of DX1002 in rat.
Keywords: tumor vascular inhibitor;pharmacokinetics;bioavailability;UPLC-MS/MS
2020, 46(10):54-58,71  收稿日期: 2020-08-20;收到修改稿日期: 2020-09-11
基金项目: 广州开发区领军人才基金(基金号:2020-L019)
作者简介: 钟卓伶(1997-),女,四川遂宁市人,硕士研究生,专业方向为药物质量控制与分析
参考文献
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