不同剂量注射用泮托拉唑钠在犬体内药代动力学研究  

Pharmacokinetic Study of Different Doses of Pantoprazole Sodium Injections in Dogs

作　　者：李冰 李晶 齐芸 韩梦禹 LI Bing;LI Jing;QI Yun;HAN Meng-yu(Yantai Saipute Analyzing Service Co.,Ltd.,Yantai,Shandong 264003,China;Shandong Asford Biotechnology Co.,Ltd.,Yantai,Shandong 264003,China)

机构地区：[1]烟台赛普特检测服务有限公司,山东烟台264003 [2]山东爱士津生物技术有限公司,山东烟台264003

出　　处：《中国兽药杂志》2025年第1期29-35,共7页Chinese Journal of Veterinary Drug

摘　　要：为研究不同剂量的泮托拉唑钠在犬体内的药代动力学特征,建立LC-MS/MS法测定犬血浆中泮托拉唑钠浓度。血浆样品采用乙腈沉淀蛋白处理后,以双氯芬酸钠为内标,采用Waters ACQUITY BEH C_(18)(2.1 mm×50 mm,1.7μm)色谱柱进行分离,以乙腈-水(含0.1%的甲酸)为流动相进行梯度洗脱,在电喷雾正离子模式下,采用多反应监测模式进行定性与定量分析。应用此方法测定静脉注射给予低(2.00 mg/kg)、中(4.00 mg/kg)、高(8.00 mg/kg)三个剂量后犬体内泮托拉唑钠的血药浓度,并使用Phoenix WinNonlin软件计算主要的药动学参数。结果显示:泮托拉唑钠在15.0~15000 ng/mL浓度范围内呈现良好线性关系(R^(2)>0.999),定量下限为15.0 ng/mL;方法的批内与批间精密度(RSD)均小于15.0%,准确度RE%在9.00%以内;方法提取回收率在95.0%~101%范围内。比格犬静脉注射三个剂量组(2.00、4.00、8.00 mg/kg)后的主要药代参数如下:AUC_(0-t)分别为7714±2256、14389±5039、41149±9193 h·ng/mL;AUC_(0-∞)分别为7748±2248、14445±5042、41250±9232 h·ng/mL;C_(0)分别为8312±2460、16135±7401、37969±16618 ng/mL;t_(1/2)分别为0.638±0.0899、0.625±0.185、0.783±0.151 h,剂量变化对t_(1/2)、V无明显影响(P>0.05)。结果表明,建立的方法简单、高效、灵敏,静脉注射不同剂量后,注射用泮托拉唑钠在犬体内代谢较快,符合线性药代动力学特征。In order to research the pharmacokinetics of pantoprazole sodium(Pan-Na)at different doses in dogs,an analytical method was established for the determination of pantoprazole sodium concentration in dog plasma by LC-MS/MS.Plasma samples were effectively extracted by acetonitrile while diclofenac sodium was used as internal standard.Separation was achieved on a Waters ACQUITY BEH C_(18)(50 mm×2.1 mm,1.7μm)column using acetonitrile-0.1%formic acid in water as the mobile phase.Under the electrospray positive ion mode,the multi-reaction monitoring mode was used for qualitative and quantitative analysis of pantoprazole.The plasma concentration of pantoprazole sodium in dogs was determined by this method after intravenous administration of three groups:low(2.00 mg/kg),medium(4.00 mg/kg)and high(8.00 mg/kg),and the main pharmacokinetic parameters were calculated by Phoenix WinNonlin software.The results indicated that pantoprazole sodium had a good linear relationship in the concentration range of 15.0~15000 ng/mL(R^(2)≥0.999)and the lower limit of quantification was 15.0 ng/mL.The intra-and inter-batch precisions(RSD)were both less than 15.0%,the accuracy RE%was within 9.00%and the recovery was between 95.0%~101%The main pharmacokinetic parameters after intravenous injection of the three dose groups(2.00 mg/kg,4.00 mg/kg and 8.00 mg/kg)in beagle dogs were as follows:AUC_(0-t)was 7714±2256 h·ng/mL,14389±5039 h·ng/mL and 41149±9193 h·ng/mL;AUC_(0-∞)was7748±2248 h·ng/mL,14445±5042 h·ng/mL and41250±9232 h·ng/mL;C_(0)was8312±2460 ng/mL,16135±7401 ng/mL and37969±16618 ng/mL;t_(1/2)was 0.638±0.0899 h,0.625±0.185 h and0.783±0.151 h.The dose change had no significant effect on t_(1/2)and V(P>0.05).The results showed that the established method was simple,efficient and sensitive,the pantoprazole sodium had a faster metabolism and met the linear pharmacokinetic characteristics in dogs after intravenous injection of different dosages.

关 键 词：泮托拉唑钠 超高效液相色谱-串联质谱联用 药动学 线性关系分析 

分 类 号：S859.794[农业科学—临床兽医学]