Page 37 - 2019年10月第30卷第20期

ABSTRACT OBJECTIVE：To establish a method for concentration determination of sinoacutine in rabbit plasma，and to conduct
its pharmacokinetic study. METHODS：The rabbits were grouped according to gender，6 rabbits in each group. Rabbits were
injected with sinoacutine solution（5 mg/kg）via ear vein. Each blood sample 1 mL was collected before medication and 5，10，15，
30，45，60，90，120，180，240 min after medcation. After the plasma isolated and extracted with ethyl acetate，HPLC method
was adopted by using sinomenine as internal standard. The determination was performed on Agilent Zorbax Extend-C18 column with
mobile phase consisted of methanol-2 mmol/L disodium hydrogen phosphate aqueous solution（containing 0.016％ triethylamine，
pH 9.8）（45 ∶ 55，V/V) at the flow rate of 1 mL/min. The detection wavelength was set at 262 nm，and column temperature was
30 ℃. The sample size was 20 μL. The pharmacokinetic parameters were calculated by using DAS 3.0 software. The difference of 2
groups were investigated by t-test. RESULTS：The linear range of sinoacutine were 0.1-5.0 mg/L；the limit of quantitation was 0.1
mg/L，and the lowest detection limit was 0.08 mg/L. RSDs of intra-day and inter-day were both less than 10％ ；the accuracy
ranged from（99.80±8.21）％-（103.61±8.55）％. The extraction method did not affect the quantitative analysis of the substance to
be measured. The average plasma-time curve of sinomenine with single intravenous injection in rabbits was in line with the
two-compartment model. The distribution half-life of all rabbits was（10.99±2.52）min，and the elimination half-life was（147.08±
32.41） min. AUC0-t was （190.82 ± 30.82）mg·min/L，and AUC0- ∞ was （289.82 ± 73.27） mg·min/L. There was no statistical
significance in pharmacokinetic parameters between female and male rabbits （P＞0.05）. CONCLUSIONS：Established HPLC
method is simple，specific and sensitive，and can be used for plasma content determination of sinoacutine. Pharmacokinetic study
shows that the pharmacokinetic process of the compound is in line with two-compartment model in rabbits. The pharmacokinetic
parameters of the compound have no sex difference，and the compound is distributed rapidly and eliminated fast.
KEYWORDS Sinoacutine；Pharmacokinetics；Rabbit；Plasma concentration；HPLC

青风藤碱（Sinoacutine，结构式见图1A）为异喹啉类
生物碱，是从防己科千金藤属云南地不容（Stephania
[1]
yunnanensis Lo）等多种植物中提取分离而得 。研究发
现，青风藤碱具有镇静、镇痛、抗炎、抗心律失常等活
性，例如青风藤碱能明显提高小鼠热板痛阈和足趾电刺
A.青风藤碱 B.青藤碱
激痛阈，减少醋酸所致的小鼠扭体次数；与戊巴比妥钠
图1 青风藤碱和青藤碱的化学结构式
[2]
联用后，可增强后者的镇静催眠作用 ；此外，青风藤碱 Fig 1 Chemical structure of sinoacutine and sinome-
还具有抗Ⅱ型胶原蛋白致大鼠类风湿性关节炎的作用， nine
并可明显降低氯仿致小鼠室颤的发生率 [3-4] 。本课题组 氮吹仪（天津市恒奥科技发展有限公司）；TGL-16G型高
前期研究发现，青风藤碱能明显缩短氯化钡致心律失常
速台式离心机（上海安亭科学仪器厂）；XK96-A 型快速
模型大鼠恢复窦性心律所需的时间。青风藤碱的结构
混匀器（姜堰市新康医疗器械有限公司）；BT25S型分析
与青藤碱（Sinomenine，结构式见图 1B）极其相似，后者
天平[赛多利斯科学仪器（北京）有限公司]；SK3300型超
具有抗炎、免疫调节、抗肿瘤、保护受损器官及镇痛等广
声机（上海科导超声仪器有限公司）；BE-1100 型四维旋
泛的药理活性 [5-7] 。目前已有多种青藤碱制剂上市，如正
转混合仪（海门市其林贝尔仪器制造有限公司）。
清风痛宁片/缓释片、盐酸青藤碱注射液等，被广泛应用
1.2 药品与试剂
于类风湿性关节炎、心率失常等症的临床治疗，效果较
青风藤碱原料药（纯度：98％）、青风藤碱对照品（纯
好 。本课题组前期研究发现，在同等剂量下，青风藤碱
[8]
度：98％）均为本实验室自制；青藤碱对照品（内标，中国
对诱导型一氧化氮合酶（iNOS）表达和c-Jun氨基末端激
食品药品检定研究院，批号：110774- 201808，纯度：供鉴
酶（JNK）磷酸化水平的抑制作用均强于青藤碱，极具开
别和含量测定用）；甲醇为色谱纯，乙酸乙酯、乙胺等其
发价值；此外，有关青藤碱及其制剂的药动学研究报道
较多 [9-12] ，而青风藤碱药动学的相关研究则较少。鉴于 余试剂均为分析纯，水为纯化水。
1.3 动物
此，本研究通过建立检测家兔血浆样品中青风藤碱质量
浓度的高效液相色谱法（HPLC），对该化合物的体内药 SPF级健康家兔12只，雌雄各半，10～12周龄，体质
动学行为进行初步探讨，旨在了解其体内代谢特征，为 量 2.0～2.5 kg，购自昆明楚商科技有限公司，动物生产
青风藤碱后续制剂的开发及临床应用提供实验依据。 许可证号：SCXK（滇）K2018-0001。
1 材料 2 方法与结果
1.1 仪器 2.1 色谱条件
1260 型 HPLC 仪（美国 Agilent 公司）；HSC-12A 型 色 谱 柱 ：Agilent Zorbax Extend-C18 （250 mm × 4.6

·2768 · China Pharmacy 2019 Vol. 30 No. 20 中国药房 2019年第30卷第20期