摘要
目的 建立测定血浆中尼莫地平含量的超高效液相色谱(ultra performance liquid chromatography,UPLC)法,并研究奥拉西坦对尼莫地平大鼠体内药动学的影响。方法 将大鼠随机分成尼莫地平组(对照组)和奥拉西坦联用尼莫地平组(联合用药组),每组6只,对照组灌胃生理盐水,联合用药组灌胃奥拉西坦200 mg·kg^(-1),连续7 d。第7天给药后禁食不禁水,第8天常规给药后,两组均灌胃尼莫地平20 mg·kg^(-1),于不同时间点取血,采用UPLC法测定血浆中尼莫地平的含量,使用DAS 2.0药动学软件分析药动学参数,使用SPSS 26.0统计软件对药动学参数进行统计分析。结果 血浆中尼莫地平的含量在50~5 000 mg·L^(-1)浓度范围内与其峰面积线性关系良好,Y=26.061X-307.974,R2=0.991;日内精密度为1.80%~3.90%;日间精密度为2.69%~12.72%;提取回收率为83.53%~87.52%;专属性、稳定性均符合要求。药动学参数显示,与对照组相比,联合用药组AUC_((0-24))、Cmax显著升高,Tmax、Vz/F显著降低,差异有统计学意义(P<0.05)。结论 本研究建立的测定大鼠血浆中尼莫地平的UPLC法灵敏度高、稳定性好、操作简便,可用于大鼠血浆中尼莫地平的测定和药动学研究;奥拉西坦会对尼莫地平药动学产生影响,奥拉西坦可加快尼莫地平的吸收速度、增加尼莫地平的生物利用度,并加速尼莫地平在大鼠体内的代谢,缩短其在大鼠体内的作用时间。
Objective:To establish a UPLC method for the determination of Nimodipine in plasma and to study the effect of Oxacetam on the pharmacokinetics of Nimodipine in rats.Methods:Rats were randomly divided into Nimodipine group(control group)and Oxacetam combined with Nimodipine group(combined group),with 6 rats in each group.The rats in the control group were gavaged with normal saline,and the rats in the combined group were gavaged with Oxacetam 200 mg·kg^(-1) for 7 consecutive days.On the 7th day after administration,fasting can’t help but cause dehydration,on the 8th day,after routine administration,both groups were intragaxed with 20 mg·kg^(-1) Nimodipine,and blood was collected at different points of time.The content of Nimodipine in plasma was determined by UPLC method.The pharmacokinetic parameters were analyzed by DAS 2.0 pharmacokinetic software,and the pharmacokinetic parametric statistics were analyzed by SPSS 26.0 statistical software.Results:The linear relationship between Nimodipine content in plasma and its peak area was good in the concentration range of 50-5000 mg·mL^(-1),Ŷ=26.061X-307.974,R2=0.991.Intra-day precision was 1.80%-3.90%;Inter-day precision was 2.69%-12.72%;The recoveries were 83.53%-87.52%;thus specificity and stability meet the requirements.Pharmacokinetic parameters showed that compared with the control group,AUC(0-24)and Cmax were significantly increased in the combined group,while Tmax and Vz/F and were significantly decreased(P<0.05).Conclusion:The UPLC method established in this study for the determination of nimodipine in rat plasma has high sensitivity,good stability,and simple operation,which can be used for the determination and pharmacokinetics research of nimodipine in rat plasma,and Oxacetam can affect the pharmacokinetics of Nimodipine.Oxacetam can accelerate the absorption rate of Nimodipine,increase the bioavailability of Nimodipine,accelerate the metabolism of Nimodipine in rats,and shorten its action time in vivo.
作者
张在美
周伟
付常芳
李玉琴
ZHANG Zaimei;ZHOU Wei;FU Changfang;LI Yuqin(School of Pharmaceutical Sciences,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250117,China;School of Pharmaceutical Sciences,Shenyang Pharmaceutical University,Shenyang 117004,China;Department of Medical Technology,Heze Health School,Heze 274000,China)
出处
《山东第一医科大学（山东省医学科学院）学报》
CAS
2024年第2期72-77,共6页
Journal of Shandong First Medical University ＆ Shandong Academy of Medical Sciences
