HPLC-MS/MS测定比格犬血浆中维他昔布浓度及其药代动力学研究  

Determination of vitacoxib in Beagle dog plasma by HPLC-MS / MS and pharmacokinetic study

作　　者：邢春宇[1,2] 李靖 孟志云[1] 吕鹏月 马飞[1] 贺艳琳[1] 冯育林[2] 窦桂芳[1] 

机构地区：[1]中国人民解放军军事医学科学院,北京100850 [2]江西中医学院,南昌330000 [3]北京欧博方医药科技有限公司,北京100085

出　　处：《药物分析杂志》2013年第11期1862-1867,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立快速灵敏的HPLC-MS/MS法测定Beagle犬血浆中维他昔布的浓度,并研究维他昔布在健康Beagle犬体内的药代动力学特征。方法:血浆样品的处理采用叔丁基甲醚液液萃取方法,内标为塞来昔布。色谱柱:Thermo Syncronic-C18(2.1 mm×100 mm,5μm);流动相:甲醇(含0.1%的甲酸)-水(含0.1%的甲酸),梯度洗脱;流速:200μL·min-1;进样量:5μL;柱温:20℃。质谱采用ESI+源,多重反应监测(MRM)模式,毛细管温度350℃,喷雾电压4.5 kV,鞘气压力199.96 kPa,辅气压力165.48 kPa,源内碰撞诱导解离电压:-10 V,碰撞气(氩气)压力0.1995 Pa,选择检测离子反应对为m/z 347.9→269.0(维他昔布),m/z 382.0→362.0(塞来昔布)。单剂量给药30 mg后,测定Beagle犬血浆中维他昔布的浓度,并计算药代动力学参数。结果:维他昔布在0.5～1000 ng·mL-1浓度范围内线性良好(r=0.9980),定量下限为0.5 ng·mL-1。提取回收率均高于89%,日间、日内RSD均小于13%,专属性良好,在本实验涉及的条件下样品稳定。Beagle犬血浆中维他昔布的C max为(94.27±57.18)ng·mL-1,T max为(2.08±2.01)h,t1/2为(5.87±3.37)h,AUC0～36 h为(625.88±375.70)h·ng·mL-1。结论:该方法简便、准确,专属性强,适用于维他昔布在Beagle犬体内的药代动力学研究。To develop a rapid, specific and sensitive HPLC - MS/MS method for the determination of vitaeoxih in Beagle dog plasma and study its pharmacokinetie characteristics in healthy Beagle dogs. Methods：The assay method involved liquid -liquid extraction of the analyte from plasma samples with methyl tert -butyl ether. Celeeoxib was used as the internal standard（IS）. The Thermo Syneronie - Cls column（2. 1 mm × 100 mm,5 μm） was used with the mobile phase of methanol （containing 0. 1% formic acid ）and water （containing 0. 1% formic acid） at the flow rate of 0. 2 mL · min-1. The injection volume was 5 μL, the column temperature was 20 ℃. The detection was performed by eleetrospray ionization mass spectrometry in the multiple reaction monitoring （MRM） mode. The positive ion scan mode was used to detect vitacoxib and celecoxib （IS）. The MRM transitions of m/z 347.9→269.0, and 382.0→362.0 were used to quantify vitacoxib and eeleeoxib （IS）. The settings of the mass spectrometer were as follows：spray voltage 4.5 kV and capillary temperature 350 ℃. The sheath gas and auxiliary gas pressures were 199.96 kPa and 165.48 kPa,respectively. The source CID voltage was - 10 V. The collision gas （argon） pressure was 0. 1995 Pa. After a single oral dose of 30 mg vitaeoxib ,the concentration and the pharmacoki-netic parameters of vitacoxib were calculated. Results：The assay was linear in the range of 0.5 -1000 ng~ mL-1 with a correlation coefficient（r） of 0. 9980. The lowest limit of quantification was 0.5 ng· mL-1. The intra - day and inter -day precision（RSDs） were lower than 13% and the extraction recovery was higher than 89%. The stabil- ity of this HPLC - MS/MS method was satisfactory too. The main pharmacokinetic parameters of C Tmax, tl/2 and AUC0_36h were（94. 27 ±57. 18）ng ·mL-1 ,（2. 08 ±2. 01）h,（5.87 ±3.37）h and（625.88 ±375.70）h ·ng · mL-1, respectively. Conclusion： The HPLC - MS/MS determination method is simple, accurate, and selective for pharm

关 键 词：维他昔布 液质联用 环氧和酶2抑制剂 比格犬 麻药浓度 药代动力学 

分 类 号：R917[医药卫生—药物分析学]