«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

25卷

期数:

2019年03期

页码:

292-295

栏目:

技术与方法

出版日期:

2019-05-20

文章信息/Info

Title:

Quantitation of paclitaxel in rats plasma by HPLC-MS/MS and its application in pharmacokinetic study

文章编号:

1006-8147(2019)03-0292-04

作者:

宋 妍

（天津医科大学第二医院药学部，天津 300211）

Author(s):

SONG Yan

（Department of Pharmacy, The Second Hospital，Tianjin Medical University，Tianjin 300211, China）

关键词:

高效液相色谱串联质谱; 紫杉醇; 药代动力学参数; 血浆

Keywords:

HPLC-MS; paclitaxel; pharmacokinetics parameter; plasma

分类号:

R9

DOI:

-

文献标志码:

A

摘要:

目的：建立一种测定大鼠血浆中紫杉醇浓度的高效液相色谱串联质谱（HPLC-MS/MS）分析方法，并研究其脂质体的药代动力学。方法：对6只SD大鼠静脉注射1 mg/kg的紫杉醇脂质体注射液，分别于给药后0、0.5、1、2、4、8、12、24、48 h自眼眶取血0.2 mL，C18反相色谱柱作为固定相，水（1 mmoL/L甲酸铵-0.05%甲酸）-甲醇作为流动相，ESI+扫描模式，MRM监测模式，药代动力学参数采用DAS 2.0软件进行计算。结果：紫杉醇在1～5 000 ng/mL范围内线性较好（R2 =0.999 7），定量下限（LLOQ）为1 ng/mL，日内和日间精密度均低于10%，紫杉醇脂质体给药后血药浓度-时间曲线满足二室模型，主要药代动力学参数t1/2、Cmax、AUC0→t分别为（4.79±0.85）h、（49 785.12±1 618.45）μg/L、（38 753.08±6 144.66）μg/L·h。结论：本方法专属性和灵敏度高，结果可靠，能满足测定大鼠血浆中紫杉醇的定量需求。

Abstract:

Objective: To establish a method for the determination of paclitaxel in rat plasma by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) and to study the pharmacokinetics of paclitaxel liposomes. Methods: Six SD rats were intravenously injected with 1 mg/kg of paclitaxel liposome. The blood samples were taken from the orbit at 0，0.5，1，2，4，8，12，24 and 48 h after administration. The C18 column was used as stationary phase, water (1 mmoL/L ammonium formate-0.05% formic acid) - methanol were chosen as mobile phase, ESI+ scanning mode, and MRM monitoring mode were chosen. The mechanical parameters were calculated by DAS 2.0 software. Results: The linearity of paclitaxel was good in the range of 1～5 000 ng/mL (R2 =0.999 7), the lower limit of quantification (LLOQ) was 1 ng/mL, and the inter-day and intra-day precisions were both less than 10%. The AUC curve of paclitaxel liposomes after administration satisfied the two-compartment model. The main pharmacokinetic parameters t1/2, Cmax and AUC0→t were(4.79±0.85) h, (49 785.12±1 618.45) μg/L, and (38 753.08±6 144.66) μg/L·h, respectively. Conclusion: The method is specific, sensitive and reliable, and may be useful in paclitaxel in rats plasma.

参考文献/References:

[1] Rajappa S, Joshi A, Doval D C, et al. Novel formulations of docetaxel, paclitaxel and doxorubicin in the management of metastatic breast cancer[J]. Oncol Lett, 2018, 16(3): 3757
[2] Zhan X K, Li J L, Zhang S, et al. Betulinic acid exerts potent antitumor effects on paclitaxel-resistant human lung carcinoma cells (H460) via G2/M phase cell cycle arrest and induction of mitochondrial apoptosis[J]. Oncol Lett, 2018, 16(3): 3628
[3] Ganipineni L P, Ucakar B, Joudiou N, et al. Magnetic targeting of paclitaxel-loaded poly(lactic-co-glycolic acid)-based nanoparticles for the treatment of glioblastoma[J]. Int J Nanomedicine, 2018, 13(1): 4509
[4] Choudhury H, Gorain B, Karmakar S, et al. Development and validation of RP-HPLC method: scope of application in the determination of oil solubility of paclitaxel[J]. J Chromatogr Sci, 2014, 52(1): 68
[5] Mo J, Eggers P K, Raston C L, et al. Development and validation of a LC/TOF MS method for the determination of carboplatin and paclitaxel in nanovesicles[J]. Anal Bioanal Chem, 2014, 406(11): 2659
[6] Liu Y, Sun J, Lian H, et al. Determination of paclitaxel in hyaluronic acid polymeric micelles in rat blood by protein precipitation-micelle breaking method: application to a pharmacokinetic study[J].J Chromatogr B Analyt Technol Biomed Life Sci, 2013, 935(18):10
[7] Chen W, Shen Y, Rong H, et al. Development and application of a validated gradient elution HPLC method for simultaneous determination of 5-fluorouracil and paclitaxel in dissolution samples of 5-fluorouracil/paclitaxel-co-eluting stents[J]. J Pharm Biomed Anal, 2012, 59(2):179
[8] Fernández-Peralbo M A, Priego-Capote F, Luque De Castro M D, et al. LC-MS/MS quantitative analysis of paclitaxel and its major metabolites in serum, plasma and tissue from women with ovarian cancer after intraperitoneal chemotherapy[J]. J Pharm Biomed Anal, 2014, 91(5):131
[9] Hendrikx J J, Rosing H, Schinkel A H, et al. Combined quantification of paclitaxel, docetaxel and ritonavir in human feces and urine using LC-MS/MS[J]. Biomed Chromatogr, 2014, 28(2): 302
[10] Cai Y, Zhang X. Pharmacokinetics of Carbon nanoparticle-paclitaxel suspension for use in intraperitoneal chemotherapy[J]. Hepatogastroenterology, 2013, 60(128): 1998
[11] Jain A, Gulbake A, Jain A, et al. Development and validation of the HPLC method for simultaneous estimation of Paclitaxel and topotecan[J]. J Chromatogr Sci, 2014, 52(7): 697
[12] Park J H, Park J H, Hur H J, et al. Effects of silymarin and formulation on the oral bioavailability of paclitaxel in rats[J]. Eur J Pharm Sci, 2012, 45(3): 296
[13] Lee J H, Lee A, Oh J H, et al. Comparative pharmacokinetic study of paclitaxel and docetaxel in streptozotocin-induced diabetic rats[J].Biopharm Drug Dispos, 2012,33(8): 474
[14] Wei Y, Xue Z, Ye Y, et al. Pharmacokinetic and tissue distribution of paclitaxel in rabbits assayed by LC-UV after intravenous administration of its novel liposomal formulation[J]. Biomed Chromatogr, 2014, 28(2): 204
[15] Zhang S Q, Song Y N, He X H, et al. Liquid chromatography-tandem mass spectrometry for the determination of paclitaxel in rat plasma after intravenous administration of poly(L-glutamic acid)-alanine- paclitaxel conjugate[J]. J Pharm Biomed Anal, 2010, 51(5): 1169
[16] Rezazadeh M, Emami J, Mostafavi A, et al. A rapid and sensitive HPLC method for quantitation of paclitaxel in biological samples using Liquid-Liquid extraction and UV detection: application to pharmacokinetics and tissues distribution study of paclitaxel loaded targeted polymeric micelles in tumor bearing mice[J]. J Pharm Pharm Sci, 2015, 18(5): 647

相似文献/References:

[1]张金曼,许 乔,马勇杰,等.AGR3在乳腺癌细胞中的功能研究[J].天津医科大学学报,2019,25(03):210.
　ZHANG Jin-man,XU Qiao,MA Yong-jie,et al.Study of the effects of AGR3 on breast cancer cell lines[J].Journal of Tianjin Medical University,2019,25(03):210.
[2]罗光泽,潘红瑞,朱杰昌,等.紫杉醇药涂球囊治疗下肢动脉闭塞症的有效性及安全性分析[J].天津医科大学学报,2019,25(04):369.
　LUO Guang-ze,PAN Hong-rui,ZHU Jie-chang,et al.Efficacy and safety of drug-coated balloon angioplasty in the treatment of lower extremity arterial occlusive disease[J].Journal of Tianjin Medical University,2019,25(03):369.

备注/Memo

备注/Memo:

作者简介 宋妍（1986-），女，药师，硕士，研究方向：药代动力学；E-mail：mackerel_272@163.com。

常用功能

更新日期/Last Update: 2019-07-03