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青风藤碱血药浓度测定及其在家兔体内的药动学研究
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| 篇名： | 青风藤碱血药浓度测定及其在家兔体内的药动学研究 |
| TITLE： | |
| 摘要： | 目的：建立检测家兔血浆中青风藤碱浓度的方法，并进行药动学研究。方法：将家兔按性别分组，每组6只。所有家兔均于耳缘静脉单次注射青风藤碱药液（5 mg/kg），分别于给药前及给药后5、10、15、30、45、60、90、120、180、240 min时于其耳缘静脉取血1 mL，分离血浆，用乙酸乙酯萃取后，以青藤碱为内标，采用高效液相色谱法（HPLC）测定。色谱柱为Agilent Zorbax Extend-C18，流动相为甲醇-2 mmol/L磷酸氢二钠水溶液（含0.016％三乙胺，pH为9.8）（45 ∶ 55，V/V），流速为1 mL/min，检测波长为262 nm，柱温为30 ℃，进样量为20 μL。采用DAS 3.0软件计算药动学参数，采用t检验考察两组的差异。结果：青风藤碱检测血药浓度的线性范围为0.1～5.0 mg/L，定量下限为0.1 mg/L，最低检测限为0.08 mg/L；日内、日间RSD均小于10％，准确度为（99.80±8.21）％～（103.61±8.55）％，提取方法不影响待测物的定量分析。家兔静脉单次注射青风藤碱的平均药-时曲线符合二室模型，所有家兔的分布半衰期为（10.99±2.52）min，消除半衰期为（147.08±32.41）min，AUC0-t为（190.82±30.82）mg·min/L，AUC0-∞为（289.82±73.27）mg·min/L；雌、雄家兔主要药动学参数组间比较，差异均无统计学意义（P＞0.05）。结论：本研究建立的HPLC法操作简便、专属性强、灵敏度高，可用于青风藤碱血药浓度的测定及药动学的研究。该化合物在家兔体内的药动学过程符合二室模型，药动学参数无性别差异，且分布迅速、消除较快。 |
| 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. |
| 期刊： | 2019年第30卷第20期 |
| 作者： | 朱丽媛，彭朝蕊，赵远翠，刘云宽，马云淑 |
| AUTHORS： | ZHU Liyuan，PENG Chaorui，ZHAO Yuancui，LIU Yunkuan，MA Yunshu |
| 关键字： | 青风藤碱；药动学；家兔；血药浓度；高效液相色谱法 |
| KEYWORDS： | Sinoacutine； Pharmacokinetics； Rabbit； Plasma concentration； HPLC |
| 阅读数： | 417 次 |
| 本月下载数： | 8 次 |
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