UPLC-MS/MS法测定Beagle犬血浆中S-奥拉西坦浓度

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (9): 988-995.

UPLC-MS/MS法测定Beagle犬血浆中S-奥拉西坦浓度

汪五三¹, 季晖¹, 谢海棠², 戴敏², 贾元威², 梁大虎², 叶雷³, 荣祖元³

¹中国药科大学药学院,南京,210009,江苏;
²皖南医学院弋矶山医院临床药学部,芜湖 241001,安徽;
³重庆东泽医药科技发展有限公司, 重庆 400030

收稿日期:2012-06-04 修回日期:2012-07-10 发布日期:2012-09-25
通讯作者: JI Hui, Corresponding author: Professor, Ph.D supervisor, Main research direction: Geriatric pharmacology. Tel: 025-86205849 E-mail: address: huijicpu@163.com
作者简介:Wang Wu-san, Ph.D, Main research direction: Geriatric pharmacology. Tel: 025-86205849 E-mail: wangyue206@yahoo.com.cn

A sensitive and specific UPLC-MS/MS analysis and preliminary pharmacokinetic characterization of S-oxiracetam in Beagle dogs

WANG Wu-san¹, JI Hui¹, XIE Hai-tang², DAI Min², JIA Yuan-wei², LIANG Da-hu², YE Lei³, RONG Zu-yuan³

¹Department of Pharmacology, China Pharmaceutical University, Nanjing 210009,Jiangsu, China;
²Department of Clinical Pharmacy,Yijishan Hospital,Wannan Medical College , Wuhu 241001, Anhui, China;
³Dong Ze Pharmaceutical Science and Technology Co. L td, Chongqing 400030 , China

Received:2012-06-04 Revised:2012-07-10 Published:2012-09-25
Contact: JI Hui, Corresponding author: Professor, Ph.D supervisor, Main research direction: Geriatric pharmacology. Tel: 025-86205849 E-mail: address: huijicpu@163.com
About author:Wang Wu-san, Ph.D, Main research direction: Geriatric pharmacology. Tel: 025-86205849 E-mail: wangyue206@yahoo.com.cn

摘要/Abstract

摘要： 目的建立灵敏、准确的Beagle犬血浆中S-奥拉西坦浓度的UPLC-MS/MS检测方法,并用于该药在Beagle犬体内的药动学研究。方法血浆样品经甲醇沉淀蛋白后,以甲醇-水溶液(85∶15, V/V,内加 10 mmoL 乙酸铵和 0.1%甲酸)为流动相,用 HP Amide LC-MS/MS Column(100 mm×3 mm ID,5 μm)分离,采用电喷雾离子源,以多反应监测(MRM)方式进行正离子检测,定量分析的离子反应分别为 m/z 159.0/114.1(S-奥拉西坦) 和 m/z 143.0/126.1(内标,吡拉西坦)。结果 S-奥拉西坦线性范围为 0.05~50 μg/mL,定量下限为 0.05 μg/mL,日内、日间精密度(RSD)均小于15%。S-奥拉西坦大鼠血浆样品在储存、预处理、分析期间均显示良好的稳定性。应用此法研究了6只Beagle犬单剂量口服S-奥拉西坦 50 mg/kg 后的药动学特点。结论该方法快速、专属、灵敏、适用性强,可应用于S-奥拉西坦的临床前药动学研究。

关键词: S-奥拉西坦, UPLC-MS/MS, 药动学, Beagle犬, 血浆

Abstract: AIM: To develop a sensitive and specific ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method for the identification and quantification of S-oxiracetamin in Beagle dog plasma.METHODS: The method involved the addition of piracetam as internal standards, protein-precipitation, UPLC separation, and quantification by MS/MS system using positive electrospray ionization in the multiple reaction monitoring mode (MRM). An HP Amide C₁₈ column (100 mm×3.00 mm, 5 μm) was used as the analytical column, while a mixture of methanol-water was used as the mobile phase. The precursor/product ion transitions selected were m/z 159.0/114.1 for S-oxiracetam and m/z 143.0/126.1 for I.S.RESULTS: The lower limit of quantification of S-oxiracetam was 0.05 μg/mL.The method was linear in the concentration range of 0.05-50 μg/mL.The intra-day and inter-day precisions (RSD) were within 15.0% for the analytes. S-oxiracetam was proved to be stable during all sample storage, preparation and analytical periods.The method was successfully applied to a pharmacokinetic study in dogs after intragastric administration of S-oxiracetam with a dose of 50 mg/kg.CONCLUSION: The proposed method enables unambiguous identification and quantification for the preliminary pharmacokinetic studies of S-oxiracetam.

Key words: S-oxiracetam, UPLC-MS/MS, Pharmacokinetics, Beagle dog, Plasma

中图分类号:

R965.2

汪五三, 季晖, 谢海棠, 戴敏, 贾元威, 梁大虎, 叶雷, 荣祖元. UPLC-MS/MS法测定Beagle犬血浆中S-奥拉西坦浓度[J]. 中国临床药理学与治疗学, 2012, 17(9): 988-995.

WANG Wu-san, JI Hui, XIE Hai-tang, DAI Min, JIA Yuan-wei, LIANG Da-hu, YE Lei, RONG Zu-yuan. A sensitive and specific UPLC-MS/MS analysis and preliminary pharmacokinetic characterization of S-oxiracetam in Beagle dogs[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(9): 988-995.

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