Analysis of Pharmacokinetic Behavior of Five Components in Qingkailing (Lyophilized) for Injection in Normal Rats and Cerebral Ischemia Rats by UPLC-MS/MS

Xue LIU; Ju SU; Peng DU; Wen-li YAO; Qing-bo YANG; Yu-mei LU; Lin-jing WU; Feng JIANG; Xiang-chun SHEN; Qian-li XU; Ling TAO; Xiang-jun MAO

doi:10.13422/j.cnki.syfjx.20191452

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Analysis of Pharmacokinetic Behavior of Five Components in Qingkailing (Lyophilized) for Injection in Normal Rats and Cerebral Ischemia Rats by UPLC-MS/MS

Drug Metabolism | 更新时间：2021-02-09

- Analysis of Pharmacokinetic Behavior of Five Components in Qingkailing (Lyophilized) for Injection in Normal Rats and Cerebral Ischemia Rats by UPLC-MS/MS
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 22, Pages: 86-91(2019)
- 作者机构：
  
  1.贵州医科大学　贵州省天然药物资源高效利用工程中心，贵州省普通高等学校天然药物药理与成药性评价特色重点实验室，贵州医科大学-贵阳市联合重点实验室，天然药物资源优效利用重点实验室，药学院，贵阳　 550025；
  2.贵州医科大学　附属医院，贵阳　 550004；
  3.贵州益佰制药股份有限公司，贵阳　 550008；
  4.贵州省食品药品检验所，贵阳　 550004
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191452
  CLC： R22; R24; R28; R969.1; C37
- Published：20 November 2019，
  
  Published Online：03 April 2019，
  
  Received：21 January 2019，
- 稿件说明：
扫描看全文
Xue LIU, Ju SU, Peng DU, et al. Analysis of Pharmacokinetic Behavior of Five Components in Qingkailing (Lyophilized) for Injection in Normal Rats and Cerebral Ischemia Rats by UPLC-MS/MS. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(22):86-91(2019)
DOI：

Xue LIU, Ju SU, Peng DU, et al. Analysis of Pharmacokinetic Behavior of Five Components in Qingkailing (Lyophilized) for Injection in Normal Rats and Cerebral Ischemia Rats by UPLC-MS/MS. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(22):86-91(2019) DOI： 10.13422/j.cnki.syfjx.20191452.

摘要

目的：

建立超高效液相色谱-质谱联用技术(UPLC-MS/MS)测定注射用清开灵(冻干)中黄芩苷、栀子苷、绿原酸、胆酸和猪去氧胆酸在大鼠血浆中含量的方法，研究该制剂在正常和脑缺血模型大鼠体内的药代动力学行为。

方法：

大鼠随机分为正常组和脑缺血模型组。采用线栓法制备大鼠脑缺血模型，以生理盐水为溶媒，腹腔注射给药，分别在相应时间点取血，经处理后使用UPLC-MS/MS测定血药浓度，主要检测条件为流动相0.1%甲酸水(A)-乙睛(B)梯度洗脱(0～0.25 min，90%A；0.25～1 min，90%～75%A；1～2 min，75%～50%A；2～2.6 min，50%～45%A；2.6～2.65 min，45%～90%A；2.65～4.0 min，90%A)，流速0.4 mL·min

－1

，柱温40 ℃，电喷雾离子源，负离子方式扫描。拟合药动学参数和计算生物利用度，分析注射用清开灵(冻干)中5种成分在正常和脑缺血模型大鼠体内处置过程的差异。

结果：

大鼠腹腔注射给予注射用清开灵(冻干)后，与正常组比较，栀子苷在脑缺血模型组大鼠体内的药-时曲线下面积(AUC

)显著降低(

0.05)，脑缺血模型组大鼠体内绿原酸的达峰时间(

max

)显著提前(

0.01)；黄芩苷、胆酸和猪去氧胆酸在2组大鼠体内的药代动力学参数均无显著性差异。

结论：

注射用清开灵(冻干)在正常和脑缺血大鼠体内的处置过程存在一定差异，对该制剂临床治疗脑缺血疾病具有一定的指导意义。

Abstract

Objective:

To establish a UPLC-MS/MS analysis method for determination of baicalin

geniposide

chlorogenic acid

cholic acid and hyodeoxycholic acid in Qingkailing (lyophilized) for injection in rat plasma

and to investigate the pharmacokinetic behavior of this preparation in normal and cerebral ischemic rats.

Method:

Rats were randomly divided into normal group and cerebral ischemia model group. The rat model of cerebral ischemia was established by suture embolization. The rats were given by intraperitoneal injection

and normal saline was used as the solvent. Blood samples were taken at the corresponding time points. After treatment

UPLC-MS/MS was used to determine the blood concentration of five components. The main detection conditions were mobile phase of 0.1%formic acid aqueous solution-acetonitrile for gradient elution (0-0.25 min

90%A; 0.25-1 min

90%-75%A; 1-2 min

75%-50%A; 2-2.6 min

50%-45%A; 2.6-2.65 min

45%-90%A; 2.65-4.0 min

90%A)

the flow rate of 0.4 mL·min

-1

the column temperature at 40 ℃

electrospray ionization under negative ion mode. The pharmacokinetic parameters were fitted and the bioavailability was calculated

the differences of treatment process of five components from Qingkailing (lyophilized) for injection in normal and cerebral ischemic rats were analyzed.

Result:

Compared with the normal group

the area under the curve (AUC

) of geniposide in rats from cerebral ischemia model group decreased significantly after intraperitoneal injection of Qingkailing (lyophilized) for injection (

0.05)

and the time to peak (

max

) of chlorogenic acid in rats from cerebral ischemia model group was significantly earlier than that in the normal group (

0.01). Pharmacokinetic parameters of baicalin

cholic acid and hyodeoxycholic acid had no significant difference between these 2 groups.

Conclusion:

Qingkailing (lyophilized) for injection has a certain difference in the treatment process between normal and cerebral ischemic rats

which has certain guiding significance for the clinical treatment of cerebral ischemic diseases with this preparation.

关键词

注射用清开灵(冻干)脑缺血模型药代动力学芦丁异鼠李素内源性胆汁酸腹腔注射

Keywords

Qingkailing (lyophilized) for injectioncerebral ischemia modelpharmacokineticsrutinisorhamnetinendogenous bile acidsintraperitoneal injection

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