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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
 

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右旋雷贝拉唑钠肠溶片在Beagle犬体内的药代动力学

Pharmacokinetic study of enteric coated (R)-rabeprazole sodium in Beagle dogs

作者(英文):
分类号:R917
出版年·卷·期(页码):2018,38 (9):1523-1529
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

目的:建立灵敏、快速的Beagle犬血浆中雷贝拉唑钠对映体及其代谢物的LC-MS/MS定量分析方法,并研究右旋雷贝拉唑钠肠溶片Beagle犬体内药代动力学特征。方法:以非那西丁为内标,血浆样品前处理以乙酸乙酯萃取,初始流动相为甲醇-水(5∶95),梯度洗脱,采用AGP 30713色谱柱分离,流速为0.5 mL·min-1,进样量5.0 μL。通过电喷雾离子源,以多重反应监测模式(MRM)进行正离子检测。采用此法测定了Beagle犬口服右旋雷贝拉唑钠肠溶片10 mg 6 h后,雷贝拉唑钠对映体及其3种代谢物的血浆药物浓度。结果:犬血浆中雷贝拉唑对映体及其3种代谢产物的线性范围为2.0~2 000 ng·mL-1,定量下限为2.0 ng·mL-1,批内、批间精密度(RSD)介于1.2%~9.9%之间。Beagle犬单次口服右旋雷贝拉唑钠肠溶片后,血浆中未检测到雷贝拉唑钠左旋体,右旋雷贝拉唑钠、硫醚雷贝拉唑、雷贝拉唑砜及去甲基雷贝拉唑的AUC(0-∞)分别为(1 486.82±956.68)、(265.03±182.16)、(79.60±45.92)、(220.10±119.90)μg·h·L-1Tmax分别为(1.33±0.42)、(1.50±0.35)、(1.42±0.43)、(1.42±0.50)h,t1/2分别为(0.35±0.12)、(1.34±1.07)、(0.43±0.07)、(0.43±0.20)h。结论:该方法可用于右旋雷贝拉唑钠肠溶片Beagle犬体内药代动力学研究,右旋雷贝拉唑钠在犬体内代谢迅速,未发现其转化为左旋体。

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

Objective: To establish a sensitive and rapid LC-MS/MS quantitative analysis method to simultaneously determine rabeprazole sodium enantiomers and their metabolites in Beagle dog plasma, and to study the pharmacokinetic characteristics of oral administration of (R)-rabeprazole sodium in vivo.Methods: The analytes and the internal standard phenacetin were extracted from plasma samples by ethyl acetate.The separation was accomplished in an AGP 30713 column, and the mobile phase consisted of methanol-water (5:95) by gradient elution at a flow rate of 0.5 mL·min-1, sample volume 5 μL.The positive ion detection was carried out by the multiple reaction monitoring model (MRM) by the electrospray ion source.The plasma concentration of rabeprazole enantiomers and its 3 metabolites in beagle dogs were determined under these conditions within 6 h after the oral administration of enteric coated (R)-rabeprazole sodium 10 mg.Results: The linear range of the rabeprazole sodium enantiomer and its 3 metabolites in dog plasma was 2.0-2000 ng·mL-1, the LOQ was 2.0 ng·mL-1, the intra-batch and inter-batch precisions (RSDs) were between 1.2%-9.9%.The AUC(0-∞) s of (R)-rabeprazole, rabeprazole thioether, rabeprazole sulfone and desmethyl rabeprazole in Beagle dogs after single oral administration of enteric coated (R)-rabeprazole sodium were (1486.82±956.68), (265.03±182.16), (79.60±45.92), (220.10±119.90)μg·h·L-1, respectively.The TmaxS were (1.33±0.42), (1.50±0.35), (1.42±0.43), (1.42±0.50) h and the t1/2s were (0.35±0.12), (1.34±1.07), (0.43±0.07), (0.43±0.20) h, respectively.No (S)-rabeprazole was detected.Conclusion: The established method is proved suitable for the pharmacokinetic study of (R)-rabeprazole sodium.The (R)-rabeprazole sodium and the metabolites can be quickly eliminated in the dog plasma but cannot be chiral biotransformed to (S)-rabeprazole.

-----参考文献:---------------------------------------------------------------------------------------

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