帕唑帕尼在大鼠体内药动学研究

周陈建; 赵嫏嬛; 胡国新

doi:10.3969/j.issn.1006-0111.2017.04.014

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

x 关闭永久关闭

应中央军委要求，2022年9月起，《药学实践杂志》将更名为《药学实践与服务》，双月刊，正文96页；2023年1月起，拟出版月刊，正文64页，数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿！

帕唑帕尼在大鼠体内药动学研究

周陈建, 赵嫏嬛, 胡国新

文章导航 > 药学实践与服务 > 2017 > 35(4): 346-349

周陈建, 赵嫏嬛, 胡国新. 帕唑帕尼在大鼠体内药动学研究[J]. 药学实践与服务, 2017, 35(4): 346-349. doi: 10.3969/j.issn.1006-0111.2017.04.014

引用本文:

周陈建, 赵嫏嬛, 胡国新. 帕唑帕尼在大鼠体内药动学研究[J]. 药学实践与服务, 2017, 35(4): 346-349. doi: 10.3969/j.issn.1006-0111.2017.04.014

ZHOU Chenjian, ZHAO Langhuan, HU Guoxin. Study on pharmacokinetics of pazopanib in rats[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(4): 346-349. doi: 10.3969/j.issn.1006-0111.2017.04.014

Citation:

ZHOU Chenjian, ZHAO Langhuan, HU Guoxin. Study on pharmacokinetics of pazopanib in rats[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(4): 346-349. doi: 10.3969/j.issn.1006-0111.2017.04.014

帕唑帕尼在大鼠体内药动学研究

doi: 10.3969/j.issn.1006-0111.2017.04.014

1.
温州市中心医院, 浙江温州 325000
2.
温州市人民医院, 浙江温州 325000
3.
温州市医科大学, 浙江温州 325000

Study on pharmacokinetics of pazopanib in rats

1.
Center Hospital of Wenzhou, Wenzhou 235000, China
2.
People's Hospital of Wenzhou, Wenzhou 235000, China
3.
Medical College of Wenzhou, Wenzhou 235000, China

摘要: 目的建立大鼠血浆中检测帕唑帕尼的超高效液相色谱-质谱（UPLC-MS）的方法，研究帕唑帕尼在大鼠体内的药动学过程。方法大鼠血浆样品用乙腈沉淀后检测。采用Acquity U-HPLC BEH C₁₈柱为分离柱，流动相采用乙腈-0.1%甲酸体系，梯度洗脱；采用AB Sciex QTRAP 5500三重四级杆质谱仪（电喷雾离子源）进行质谱检测，帕唑帕尼和内标地西泮采用多反应监测（MRM）的方法检测，帕唑帕尼和内标地西泮（ISTD）的MRM分别为m/z 438.3→357.2 和 m/z 285.2→193.1；雄性SD大鼠6只，灌胃给予80 mg/kg 帕唑帕尼，在给药前和给药后的不同时间点于大鼠尾静脉取血。用建立的方法测定血浆中帕唑帕尼的浓度。用DAS 3.0计算主要药动学参数。结果大鼠血浆中帕唑帕尼浓度在0.25~40.00 μg/ml范围内线性关系良好（r=0.999 2）；低、中、高3个质量浓度（0.50、10.00、30.00 μg/ml）的日内精密度RSD分别为6.17%、2.73%和2.54 %，日间精密度RSD分别为7.56%、5.98%和2.84%，回收率分别为（78.4±4.8）%、（85.9±3.5）%和（81.1±4.2）%，基质效应分别为（106.7±5.3）%、（101.3±6.7）%和（97.6±4.4）%；血浆帕唑帕尼的主要药动学参数：峰值浓度c_max为（20.22±1.95）μg/ml，达峰时间t_max为（1.75±0.76）h，半衰期t_1/2为（7.35±2.31）h，药-时曲线下面积AUC_0-t为（213.16±39.92）μg·h/L，AUC_0-∞为（215.79±39.84）μg·h/L，表观分布容积Vd为（4.10±1.78）L/kg，清除率CL为（0.38±0.07）L/h。用房室模型拟合，帕唑帕尼在大鼠体内呈一级消除的二室模型。结论本研究建立用UPLC-MS检测大鼠血浆帕唑帕尼的方法，专属性高，分离完全，检测时间短；适合帕唑帕尼的药动学和药物相互作用研究。
- 帕唑帕尼 /
- 超高效液相色谱-质谱 /
- 药动学
Abstract: Objective To develop a UPLC-MS method for the determination of pazopanib in rat plasma, and study the pharmacokinetics of pazopanib in rats. Methods The effective UPLC MS/MS separation of the examined compounds was applied on an Acquity BEH C₁₈ column with a gradient mobile phase system. AB Sciex QTRAP 5500 triple quadruple mass spectrometer equipped with an electrospray ionization (ESI) interface was used for mass spectrometric detection. The MRM transitions of m/z 438.3→357.2 and m/z 285.2→193.1 were used to quantify for pazopanib and ISTD, respectively; 6 rats were given 80 mg/kg pazopanib intragastric administration. Blood samples were collected from the tail vein at different point after administration. The concentration of pazopanib in plasma was detected by the UPLC-MS methods. The pharmacokinetics parameters were analyzed by DAS program. Results Pazopanib and ISTD were eluted at 1.10 and 1.37 min respectively. Excellent liner relationship was obtained from the range of 0.25 μg/ml to 40.00 μg/ml (r=0.999 2). The intra-day RSD were 6.17%, 2.73% and 2.54% and inter-day RSD were 7.56%, 5.98% and 2.84% respectively at three concentrations (0.50, 10.00, 30.00 μg/ml), the recoveries were (78.4±4.8)%, (85.9±3.5)% and (81.1±4.2)% respectively, the Matrix effect were (106.7±5.3) %, (101.3±6.7) % and (97.6±4.4) % respectively at three concentrations (0.50, 10.00, 30.00 μg/ml); 6 rats were given 80 mg/kg pazopanib intra-gastric administration. The main pharmacokinetics parameters of pazopanib were as following: c_max (20.22±1.95) μg/ml,t_max (1.75±0.76) h,t_1/2 (7.35±2.31) h,AUC_0-t (213.16±39.92) μg·h/L,AUC_0-∞ (215.79±39.84) μg·h/L,Vd (4.10±1.78) L/kg,CL (0.38±0.07) L/h. Conclusion The method was simple, rapid, accurately,which could be used to determine the pazopanib concentration in rat plasma and study on its pharmacokinetics. Pazopanib was fitted to the first-order elimination kinetics in rats.
- pazopanib /
- UPLC-MS /
- pharmacokinetics

[1]	Ranieri G, Mammì M, Donato Di Paola E,et al. Pazopanib a tyrosine kinase inhibitor with strong anti-angiogenetic activity: A new treatment for metastatic soft tissue sarcoma[J]. Crit Rev Oncol Hematol,2014,89(2):322-329.
[2]	Hamberg P, Verweij J, Sleijfer S. (Pre-)clinical pharmacology and activity of pazopanib, a novel multikinase angiogenesis inhibitor[J].Oncologist,2010,15(6):539-547.
[3]	Motzer RJ,Hutson TE,Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma[J]. N Engl J Med,2013,369(8):722-731.
[4]	Welsh SJ,Fife K. Pazopanib for the treatment of renal cell carcinoma[J]. Future Oncol,2015,11(8):1169-1179.
[5]	Dziadosz M,Lessig R,Bartels H. HPLC-DAD protein kinase inhibitor analysis in human serum[J].J Chromatogr B Analyt Technol Biomed Life Sci,2012,893-894:77-81.
[6]	Minocha M, Khurana V, Mitra AK. Determination of pazopanib (GW-786034) in mouse plasma and brain tissue by liquid chromatography-tandem mass spectrometry (LC/MS-MS)[J]. J Chromatogr B Analyt Technol Biomed Life Sci,2012, 901:85-92.

[1]	夏哲炜, 曾垣烨, 朱海菲, 李育, 陈啸飞. 核磁共振磷谱法测定磷酸氢钙咀嚼片中药物含量 . 药学实践与服务, 2024, 42(9): 399-401, 406. doi: 10.12206/j.issn.2097-2024.202404063
[2]	迟文雅, 袁艳, 李伟林, 吴茼妤, 俞媛. 负载骨髓间充质干细胞/白藜芦醇脂质体的水凝胶支架用于创伤性脑损伤治疗 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202406034
[3]	桂明珠, 李静, 李志玲. 儿童伏立康唑的血药浓度与CYP2C19、CYP2C9和CYP3A5基因多态性的相关性研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202402020
[4]	杨嘉宁, 赵一颖, 肖伟. 七味脂肝方对非酒精性脂肪性肝炎动物模型的药效学评价 . 药学实践与服务, 2024, 42(9): 389-398. doi: 10.12206/j.issn.2097-2024.202404096
[5]	赖立勇, 夏天爽, 徐圣焱, 蒋益萍, 岳小强, 辛海量. 中药青蒿抗氧化活性的谱效关系研究 . 药学实践与服务, 2024, 42(5): 203-210, 216. doi: 10.12206/j.issn.2097-2024.202211012
[6]	舒飞, 孙蕊, 宋凯, 张元林, 闫家铭, 舒丽芯. 粉-液双室袋产品综合评估 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202312009
[7]	石晓萍, 吕迁洲, 李晓宇, 许青. 泊沙康唑对比伏立康唑经验治疗或诊断驱动治疗免疫功能低下患者侵袭性霉菌病的成本-效果分析 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202401050
[8]	何静, 安晔, 张朝绅. 复方黑参滴丸与复方黑参丸药效学实验比较研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404009
[9]	凯丽比努尔·奥布力艾散, 李倩, 谢志, 贾文彦, 尹东锋. 星点设计-效应面法优化仑伐替尼混合胶束的制备工艺 . 药学实践与服务, 2024, 42(11): 495-502. doi: 10.12206/j.issn.2097-2024.202403019
[10]	崔晓林, 付晓菲, 杜艳红, 刘娟, 朱茜, 刘子祺. 临床药师参与吉瑞替尼致QTc间期延长的病例分析 . 药学实践与服务, 2024, 42(6): 263-266. doi: 10.12206/j.issn.2097-2024.202309050
[11]	杨凤艳, 张月, 陈恩贤, 缪雪蓉, 魏凯. 瑞马唑仑临床应用研究进展 . 药学实践与服务, 2024, 42(9): 365-374. doi: 10.12206/j.issn.2097-2024.202405026
[12]	唐淑慧, 凤美娟, 薛智霞, 鲁桂华. 帕博利珠单抗治疗所致免疫相关不良反应与中医体质的相关性研究 . 药学实践与服务, 2024, 42(5): 217-222. doi: 10.12206/j.issn.2097-2024.202311029
[13]	宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅. 帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(8): 334-340. doi: 10.12206/j.issn.2097-2024.202303023
[14]	崔亚玲, 吴琼, 马良煜, 胡北, 姚东, 许子华. 肝素钠肌醇烟酸酯乳膏中肌醇烟酸酯皮肤药动学研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404006
[15]	陈炳辰, 佟达丰, 万苗, 闫飞虎, 姚建忠. UPLC-MS/MS法测定小鼠血浆中紫杉醇脂肪酸酯前药及其药代动力学研究 . 药学实践与服务, 2024, 42(8): 341-345. doi: 10.12206/j.issn.2097-2024.202404082
[16]	张艺昕, 关欣怡, 王博宁, 闻俊, 洪战英. 二氢吡啶类钙离子拮抗药物手性分析及其立体选择性药动学研究进展 . 药学实践与服务, 2024, 42(8): 319-324. doi: 10.12206/j.issn.2097-2024.202308062

点击查看大图

计量

文章访问数: 3833
HTML全文浏览量: 273
PDF下载量: 638
被引次数: 0

帕唑帕尼在大鼠体内药动学研究

doi: 10.3969/j.issn.1006-0111.2017.04.014

1. 温州市中心医院, 浙江温州 325000

2. 温州市人民医院, 浙江温州 325000

3. 温州市医科大学, 浙江温州 325000

收稿日期: 2016-12-19
修回日期: 2017-02-17

关键词:

帕唑帕尼 /

超高效液相色谱-质谱 /

药动学

摘要: 目的建立大鼠血浆中检测帕唑帕尼的超高效液相色谱-质谱（UPLC-MS）的方法，研究帕唑帕尼在大鼠体内的药动学过程。方法大鼠血浆样品用乙腈沉淀后检测。采用Acquity U-HPLC BEH C₁₈柱为分离柱，流动相采用乙腈-0.1%甲酸体系，梯度洗脱；采用AB Sciex QTRAP 5500三重四级杆质谱仪（电喷雾离子源）进行质谱检测，帕唑帕尼和内标地西泮采用多反应监测（MRM）的方法检测，帕唑帕尼和内标地西泮（ISTD）的MRM分别为m/z 438.3→357.2 和 m/z 285.2→193.1；雄性SD大鼠6只，灌胃给予80 mg/kg 帕唑帕尼，在给药前和给药后的不同时间点于大鼠尾静脉取血。用建立的方法测定血浆中帕唑帕尼的浓度。用DAS 3.0计算主要药动学参数。结果大鼠血浆中帕唑帕尼浓度在0.25~40.00 μg/ml范围内线性关系良好（r=0.999 2）；低、中、高3个质量浓度（0.50、10.00、30.00 μg/ml）的日内精密度RSD分别为6.17%、2.73%和2.54 %，日间精密度RSD分别为7.56%、5.98%和2.84%，回收率分别为（78.4±4.8）%、（85.9±3.5）%和（81.1±4.2）%，基质效应分别为（106.7±5.3）%、（101.3±6.7）%和（97.6±4.4）%；血浆帕唑帕尼的主要药动学参数：峰值浓度c_max为（20.22±1.95）μg/ml，达峰时间t_max为（1.75±0.76）h，半衰期t_1/2为（7.35±2.31）h，药-时曲线下面积AUC_0-t为（213.16±39.92）μg·h/L，AUC_0-∞为（215.79±39.84）μg·h/L，表观分布容积Vd为（4.10±1.78）L/kg，清除率CL为（0.38±0.07）L/h。用房室模型拟合，帕唑帕尼在大鼠体内呈一级消除的二室模型。结论本研究建立用UPLC-MS检测大鼠血浆帕唑帕尼的方法，专属性高，分离完全，检测时间短；适合帕唑帕尼的药动学和药物相互作用研究。

English Abstract

Study on pharmacokinetics of pazopanib in rats

1. Center Hospital of Wenzhou, Wenzhou 235000, China

2. People's Hospital of Wenzhou, Wenzhou 235000, China

3. Medical College of Wenzhou, Wenzhou 235000, China

Received Date: 2016-12-19
Rev Recd Date: 2017-02-17

Keywords:

Abstract: Objective To develop a UPLC-MS method for the determination of pazopanib in rat plasma, and study the pharmacokinetics of pazopanib in rats. Methods The effective UPLC MS/MS separation of the examined compounds was applied on an Acquity BEH C₁₈ column with a gradient mobile phase system. AB Sciex QTRAP 5500 triple quadruple mass spectrometer equipped with an electrospray ionization (ESI) interface was used for mass spectrometric detection. The MRM transitions of m/z 438.3→357.2 and m/z 285.2→193.1 were used to quantify for pazopanib and ISTD, respectively; 6 rats were given 80 mg/kg pazopanib intragastric administration. Blood samples were collected from the tail vein at different point after administration. The concentration of pazopanib in plasma was detected by the UPLC-MS methods. The pharmacokinetics parameters were analyzed by DAS program. Results Pazopanib and ISTD were eluted at 1.10 and 1.37 min respectively. Excellent liner relationship was obtained from the range of 0.25 μg/ml to 40.00 μg/ml (r=0.999 2). The intra-day RSD were 6.17%, 2.73% and 2.54% and inter-day RSD were 7.56%, 5.98% and 2.84% respectively at three concentrations (0.50, 10.00, 30.00 μg/ml), the recoveries were (78.4±4.8)%, (85.9±3.5)% and (81.1±4.2)% respectively, the Matrix effect were (106.7±5.3) %, (101.3±6.7) % and (97.6±4.4) % respectively at three concentrations (0.50, 10.00, 30.00 μg/ml); 6 rats were given 80 mg/kg pazopanib intra-gastric administration. The main pharmacokinetics parameters of pazopanib were as following: c_max (20.22±1.95) μg/ml,t_max (1.75±0.76) h,t_1/2 (7.35±2.31) h,AUC_0-t (213.16±39.92) μg·h/L,AUC_0-∞ (215.79±39.84) μg·h/L,Vd (4.10±1.78) L/kg,CL (0.38±0.07) L/h. Conclusion The method was simple, rapid, accurately,which could be used to determine the pazopanib concentration in rat plasma and study on its pharmacokinetics. Pazopanib was fitted to the first-order elimination kinetics in rats.