关闭
 
读者在线:用户名 密码
首页 期刊简介 投稿须知 期刊目录 专家风采 编委会 特邀顾问 联系我们 移动出版
  1. 1
  2. 2
  3. 3
  4. 4
  5. 5



刊物信息

期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

访问统计
您是第  3 0 8 2 1 3 9 位浏览者
您当前的位置:首页 >> 正文

LC-MS/MS法测定大鼠脑组织中奥拉西坦的浓度

Concentration determination of oxiracetam in rat brain by LC-MS/MS

作者(英文):
分类号:R917
出版年·卷·期(页码):2018,38 (11):1952-1959
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

目的:建立一种简便、快速的LC-MS/MS法测定大鼠脑组织中奥拉西坦的浓度,并对SD大鼠静脉注射奥拉西坦后的脑组织分布进行研究。方法:SD大鼠脑组织样品用0.9%氯化钠溶液匀浆后,以吡拉西坦为内标,用乙腈沉淀蛋白,采用LC-MS/MS系统进行分离和测定。色谱柱为Agilent Poroshell 120 SB-C18柱(100 mm×4.6 mm,2.7 μm),流动相为30%甲醇-70%水(含10 mmol·L-1甲酸铵,0.1%甲酸),流速为0.2 mL·min-1,柱温为30℃。质谱条件:电喷雾离子源(ESI),正离子模式,多反应离子监测(MRM),检测离子为奥拉西坦m/z 158.6→ 113.6,内标吡拉西坦m/z 142.6→125.4。SD大鼠分别单次静脉注射奥拉西坦500、1 000、2 000 mg·kg-1,于不同时间点分别采集脑组织,测定脑组织中奥拉西坦的浓度。结果:SD大鼠脑组织匀浆液质量浓度在1.0~100.0 μg·mL-1范围内线性关系良好,定量下限为1.0 μg·mL-1,批内和批间精密度RSD均小于5.7%,准确度为96.3%~105.2%。大鼠分别单次静脉注射500、1 000、2 000 mg·kg-1 3个剂量的奥拉西坦后,主要药动学参数t1/2分别为(3.56±0.27)h、(3.36±0.49)h、(3.60±0.79)h,Cmax分别为(24.78±16.06)μg·g-1、(50.79±25.92)μg·g-1、(82.21±19.33)μg·g-1,MRT0-t分别为(2.54±0.02)h、(2.38±0.30)h、(2.57±0.08)h,AUC0-t分别为(48.59±10.92)μg·h·g-1、(94.54±9.30)μg·h·g-1、(201.35±18.87)μg·h·g-1结论:本测定方法可用于大鼠奥拉西坦药代动力学在脑组织中的分布研究;大鼠分别单次静脉注射3个剂量的奥拉西坦后,奥拉西坦进入脑组织的时间较快,浓度较高,持续时间较长,利于发挥活化和改善脑组织功能的作用。

-----英文摘要:---------------------------------------------------------------------------------------

Objective: To develop a simple and rapid HPLC-MS/MS method for the determination of oxiracetam concentration in rat brain tissue,and to study the distribution of oxiracetam in the brain tissues after being injected intravenously in SD rats.Methods: The tissue samples of SD rat brain were firstly homogenized with 0.9% sodium chloride solution.Using piracetam as an internal standard(IS) and acetonitrile as a protein precipitant,the samples were separated and determined by LC-MS/MS system.Agilent Poroshell 120 SB-C18 analytical column(100 mm×4.6 mm 2.7 μm) was used in the system,and the mobile phase was prepared with methanol and water in a volume ratio of 30:70,containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid. The flow rate was 0.2 mL·min-1 and the column temperature was set at 30℃.The parameters for MS were as follows:electrospray ionization source(ESI) was operated in positive ion mode;the quantification was performed using multiple reaction monitoring(MRM) mode to monitor the precursor-to-product ion transitions of m/z 158.6 → 113.6 for oxiracetam and m/z 142.6 → 125.4 for the internal standard piracetam.SD rats were injected intravenously with single doses of 500,1 000 and 2 000 mg·kg-1 oxiracetam,respectively.The rat brain tissues were collected at different time intervals and the concentrations of oxiracetam in the brain tissues were determined.Results: The linear calibration curve of oxiracetam was obtained in the concentration range of 1.0-100.0 μg·mL-1,and the lower limit of quantification(LLOQ) was 1.0 μg·mL-1. Both the intra-and inter-batch precisions of RSD were less than 5.7%.The accuracy was in the range of 96.3%-105.2%.The main pharmacokinetic parameters of oxiracetam in SD rats brain tissue after a single dose of 500,1 000,2 000 mg·kg-1 oxiracetam by intravenous route were as follows:t1/2=(3.56±0.27) h,(3.36±0.49) h,(3.60±0.79) h;Cmax=(24.78±16.06)μg·g-1,(50.79±25.92)μg·g-1,(82.21±19.33)μg·g-1;MRT0-t=(2.54±0.22) h,(2.38±0.30) h,(2.57±0.08) h;AUC0-t=(48.59±10.92)μg·h·g-1,(94.54±9.30)μg·h·g-1,(201.35±18.87)μg·h·g-1.Conclusion: The method can be used to investigate the pharmacokinetics of oxiracetam distributed in rat brain tissues.After being injected intravenously with a single dose of oxiracetam at 3 dosages,the uptake of oxiracetam into the brain tissue is very quick,maintained at a high concentration with a long duration.All the actions promote the activation and improvement of the brain functions.

-----参考文献:---------------------------------------------------------------------------------------
[1] 齐洪武,王政刚,程建业.促智药奥拉西坦的研究进展[J].实用医院临床杂志,2010,7(5):147 QI HW,WANG ZG,CHENG JY.Advances in nootropics drugs:a study of oxiracetam[J].Pract J Clin Med,2010,7(5):147
[2] PONZIO F,POZZI O,BANFI S,et al.Brain entry and direct central pharmacological effects of the nootropic drug oxiracetam[J].Pharmacopsychist,1989,22:111
[3] VILLARDITA C,GRIOLI S,LOMEO C,et al.Clinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree[J].Neuropsychobiology,1992,25(1):24
[4] 刘治军,胡欣.促智药奥拉西坦的临床和基础研究[J].中华神经外科疾病研究杂志,2005,4(3):286 LIU ZJ,HU X.The clinical and fundamental research of the nootropic drug-oxiracetam[J].Chin J Neurosurg Dis Res,2005,4(3):286
[5] 王敬,张杰,周杰.奥拉西坦和吡拉西坦治疗脑器质性综合症临床疗效的系统评价[J].中国循证心血管医学杂志,2016,8(2):160 WANG J,ZHANG J,ZHOU J.Systematic review of curative effects of oxiracetam and piracetam on treatment of cerebral organic syndrome[J].Chin J Evid Base Cardiovasc Med,2016,8(2):160
[6] YAO XL,YAO ZH,LI L,et al.Oxiracetam can improve cognitive impairment after chronic cerebral hypoperfusion in rats[J].Psychiatry Res,2016,246(30):284
[7] 郭晶晶.奥拉西坦对脑梗死急性期认知功能障碍和脑血流量的改善作用[J].白求恩医学杂志,2017,15(2):190 GUO JJ.The improvement of effects of oxiracetam on cognitive impairment in acute stage of cerebral infarction and cerebral blood flow[J].J Bethune Med Sci,2017,15(2):190
[8] 金磊,李博,叶雷,等.奥拉西坦的临床前药理学研究[J].中国临床药理学与治疗学,2011,16(3):354 JIN L,LI B,YE L,et al.Preclinical pharmacology research of oxiracetam[J].Chin J Clin Pharmacol Ther,2011,16(3):354
[9] 李坤,王瑛瑛,于媛媛.促智药物(S)奥拉西坦的合成[J].中国新药杂志,2011,20(19):1920 LI K,WANG YY,YU YY.Synthesis of the nootropic drug S-stereoisomer of oxiracetam[J].Chin J New Drugs,2011,20(19):1920
[10] 李获,张晓宇.奥拉西坦在犬体内的药动学研究[J].中国药房,2013,24(37):3473 LI H,ZHANG XY.Study on pharmacokinetics of oxiracetam in dogs[J].China Pharm,2013,24(37):3473
[11] 陈倩,刘东,张东林,等.奥拉西坦颗粒在健康人体中药动学和生物等效性[J].中国医院药学杂志,2012,32(1):14 CHEN Q,LIU D,ZHANG DL,et al.Pharmacokinetics and bioequivalence of oxiracetam granules in healthy volunteers[J].Chin J Hosp Pharm,2012,32(1):14
[12] 刘杰,张国顺,赵云丽,等.奥拉西坦口服溶液的人体生物等效性评价[J].沈阳药科大学学报,2012,29(4):284 LIU J,ZHANG GS,ZHAO YL,et al.Bioequivalence of oxiracetam oral solutions[J].J Shenyang Pharm Univ,2012,29(4):284
[13] 梁大虎,孙华,袁小龙,等.手性固定相HPLC法测定人血浆中奥拉西坦2种异构体的浓度[J].药物分析杂志,2016,36(5):776 LIANG DH,SUN H,YUAN XL,et al.A chiral stationary phase HPLC method for oxiracetam enantiomers determination in Chinese healthy volunteers' plasma[J].Chin J Pharm Anal,2016,36(5):776
[14] 张佩婷,王志仁,周玉婷,等.奥拉西坦光学对映体在多糖类手性固定相上的拆分[J].药物分析杂志,2014,34(2):287 ZHANG PT,WANG ZR,ZHOU YT,et al.Separation of oxiracetam optical enantiomers using polysaccharide chiral stationary phase[J].Chin J Pharm Anal,2014,34(2):287
[15] ZHANG QY,YANG W,YANG Y,et al.Comparative pharmacokinetic studies of racemic oxiracetam and its pure enantiomers after oral administration in rats by a stereoselective HPLC method[J].J Pharm Biomed Anal,2015,111:153
[16] ZHANG QY,YANG W,ZhANG Q,et al.Enantioselective HPLC determination of oxiracetam enantiomers and application to a pharmacokinentic study in Beagle dogs[J].J Chromatogr B,2015,9(13):993
[17] 朱荣华,万顺,颜苗,等.注射用奥拉西坦人体药动学研究[J].中南药学,2011,9(9):651 ZHU RH,WAN S,YAN M,et al.Pharmacokinetics of oxiracetam for injection in Chinese healthy volunteers[J].Cent South Pharm,2011,9(9):651
[18] 张丹,杨漫,张娅喃,等.LC-MS/MS法测定人血浆中奥拉西坦的浓度及其两种口服制剂在健康中国人体的生物等效性(英文)[J].中国新药与临床杂志,2014,33(4):281 ZHANG D,YANG M,ZHANG YN,et al.LC-MS/MS method for quantitation of oxiracetam in human plasma:application to a bioequivalence study of its two oral formulations in healthy Chinese subjects[J].Chin J New Drugs Clin Rem,2014,33(4):281
[19] JUNGHYUN S,JAEICK L,MIJIN L,et al.Rapid quantitative analysis of oxiracetam in human plasma by liquid chromatography/electrospray tandem mass spectrometry[J].J Pharm Biomed Anal,2004,36(3):657
[20] WANG WS,JI H,XIE HT,et al.A sensitive and specific UPLC-MS/MS analysis and perliminary pharmacokinetic characterization of S-oxiracetam in Beagle dogs[J].Chin J Pharmacol Ther,2012,17(9):988
[21] SHIGETOH H,YAMAGAMI S,UNO K,et al.A pharmacokinetics study of oxiracetam in rats(Ⅰ):plasma levels profile,tissue,distribution,metabolism and excretion after single administration[J].Drug Metab Pharmacokinet,1991,6(4):637
[22] TIZIANA M,CARLO T,ALFREDO C,et al.In-vivo radiolabelled oxiracetam binding to rat brain[J].J Pharm Pharmacol,1990,42(3):171
[23] 沈园园,岳鹏,乔红群.LC-MS/MS测定左旋奥拉西坦及其在SD大鼠生殖毒性中体内组织分布检测[J].药物分析杂志,2017,36(6):1056 SHEN YY,YUE P,QIAO HQ.LC-MS/MS method for quantitation of S-oxiracetam and its application to the research of SD rat tissue distribution in reproductive toxicity[J].Chin J Pharm Anal,2017,36(6):1056

欢迎阅读《药物分析杂志》!您是该文第 98位读者!

药物分析杂志 © 2009
地址:北京天坛西里2号
邮政编码:100050; 技术支持:010-60213898

电子邮件:ywfx@nicpbp.org.cn