Page 19 - 《中国药房》2021年22期

·药学研究·

LC-MS/MS法测定大鼠血浆中芦荟苦素浓度及其药动学研究 Δ

谭银丰 ，孙墨箫，张 蕾，杨雯悦，李海龙，李友宾（海南医学院药学院/海南省热带药用植物研究开发重点实验
＊
#
室/海口市黎族医药重点实验室，海口 571159）

中图分类号 R969.1 文献标志码 A 文章编号 1001-0408（2021）22-2701-05
DOI 10.6039/j.issn.1001-0408.2021.22.03

摘 要 目的：建立测定大鼠血浆中芦荟苦素浓度的方法，并考察芦荟苦素的药动学特征。方法：血浆样品经甲醇沉淀蛋白后，以
芦荟新苷D为内标，采用液相色谱-串联质谱法测定大鼠血浆中芦荟苦素的血药浓度。以Synergi Hydro-RP为色谱柱，以0.1‰甲
酸溶液-甲醇为流动相进行梯度洗脱，流速为0.50 mL/min，柱温为30 ℃，进样量为5 µL；采用电喷雾离子源，以多反应监测模式进
行负离子检测，用于定量分析的离子对分别为m/z 393.1→272.9（芦荟苦素）、m/z 555.3→144.9（内标）。采用上述方法测定大鼠尾
静脉注射（3.35 mg/kg）和灌胃（16.75 mg/kg）芦荟苦素后0.083、0.167、0.333、0.667、1、1.5、2.5、4、6、8、10 h静脉血中芦荟苦素的质量
浓度，采用DAS 3.0软件计算药动学参数。结果：芦荟苦素检测质量浓度的线性范围为1～600 ng/mL（r＝0.994 5），定量下限为1
ng/mL，批内、批间RSD均小于15％，批内、批间准确度在±15％内，基质因子为（92.74±4.33）％～（94.84±2.57）％，提取回收率为
（69.04±2.13）％～（75.03±2.84）％，稳定性试验的实测结果与理论值的偏差在±15％内。大鼠静脉注射和灌胃芦荟苦素后，主要
药动学参数cmax分别为（10 693.3±2 745.3）、（223.3±36.2）ng/mL，t1/2分别为（2.45±1.45）、（3.33±1.91）h，AUC0－24 h分别为（4 190.6±
883.6）、（1 210.1±93.9）ng·h/mL（n＝3），口服绝对生物利用度为11.13％。结论：本研究成功建立了一种快速、灵敏的芦荟苦素血
药浓度测定方法，适用于其药动学研究。
关键词 芦荟苦素；芦荟新苷D；血药浓度；药动学；液相色谱-串联质谱法；大鼠

Determination of Aloesin in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Study
TAN Yinfeng，SUN Moxiao，ZHANG Lei，YANG Wenyue，LI Hailong，LI Youbin（School of Pharmacy，Hainan
Medical University/Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs/Haikou
Key Laboratory of Li Nationality Medicine，Haikou 571159，China）

ABSTRACT OBJECTIVE：To establish a method for the determination of aloesin in plasma of rats，and to investigate
pharmacokinetic characteristics of aloesin. METHODS：The plasma samples were precipitated with methanol. Using aloeresin D as
internal standard，the plasma concentration of aloesin was determined by LC-MS/MS. The determination was performed on Synergi
Hydro-RP column with mobile phase consisted of 0.1‰ formic acid-methanol（gradient elution）at the flow rate of 0.50 mL/min.
The column temperature was 30 ℃，and sample size was 5 µL. The electrospray ionization source was applied to carry out negative
ion detection with multiple reaction monitoring mode. The ion transitions for quantitative analysis were m/z 393.1→272.9（aloesin）
and m/z 555.3→144.9（internal standard），respectively. The concentration of aloesin in venous blood was determined by above
method at 0.083，0.167，0.333，0.667，1，1.5，2.5，4，6，8，10 h after intravenous injection （3.35 mg/kg） and intragastric
administration（16.75 mg/kg）of aloesin. DAS 3.0 software was used to calculate pharmacokinetic parameters. RESULTS：The
linear range of aloesin were 1-600 ng/mL（r＝0.994 5）. The lower limit of quantification was 1 ng/mL，and RSDs of within and
between batches were less than 15％；accuracies within and between batches were within ±15％. The matrix factors were（92.74±
4.33）％-（94.84±2.57）％，and extraction recoveries were（69.04±2.13）％-（75.03±2.84）％；the deviation between the measured
results of the stability test and the theoretical values were within±15％. After intravenous injection and intragastric administration
of aloesin，main pharmacokinetic parameters were as follows：cmax were（10 693.3±2 745.3）and（223.3±36.2）ng/mL；t1/2 were
（2.45±1.45）and（3.33±1.91）h；AUC0－24 h were（4 190.6±883.6）and（1 210.1±93.9）ng·h/mL（n＝3）. Absolute bioavailabi-
lity was 11.13％. CONCLUSIONS：The established method is
Δ 基金项目：国家自然科学基金资助项目（No.81460591）；海南医
学院2020年大学生创新创业训练计划项目（No.S202011810009） rapid and sensitive for plasma determination of aloesin，and
＊副研究员，硕士。研究方向：中药药动学。E-mail：hy0207059@ suitable for its pharmacokinetic study.
hainm.edu.cn KEYWORDS Aloesin；Aloeresin D；Plasma concentration；
# 通信作者：研究员，硕士生导师，博士。研究方向：天然药物化 Pharmacokinetics；LC-MS/MS；Rats
学。电话：0898-66890907。E-mail：liyoubinli@sohu.com

中国药房 2021年第32卷第22期 China Pharmacy 2021 Vol. 32 No. 22 ·2701 ·