摘要
本文建立了一种快速、灵敏、简便的可同时测定Beagle犬全血中丁酸氯维地平及其代谢产物氯维地平酸的液相色谱-串联质谱方法。全血样品经甲醇沉淀蛋白后,以甲醇-5 mmol·L-1甲酸铵水溶液为流动相,通过Ecosil C18（150 mm×4.6 mm,5μm）梯度洗脱,色谱运行时间为13.0 min。质谱检测条件为电喷雾离子源多反应监测模式,定量离子对为m/z 454.1[M-H]-→234.1（丁酸氯维地平）,m/z 354.0[M-H]-→208.0（氯维地平酸）,m/z256.1[M-H]-→227.1（乙氧苯柳胺,内标）。测定Beagle犬全血中丁酸氯维地平及其代谢物的标准曲线线性范围分别为0.5～100和1～200 ng·m L-1,定量下限分别为0.5和1 ng·m L-1,日内和日间精密度（RSD）均小于12.9%。应用建立的定量方法成功地研究了Beagle犬静脉输注（5 mg·h-1）丁酸氯维地平注射液30 min后药动学特征。
A rapid, sensitive and simple liquid chromatography-tandem mass spectrometry （LC-MS/MS） method was developed and validated for the simultaneous determination of clevidipine butyrate and its primary metabolite clevidipine acid in dog blood. After one-step protein precipitation with methanol, the chromatographic separation was carried out on an Ecosil C18（150 mm×4.6 mm,5μm）） with a gradient mobile phase consisting of methanol and 5 mmol·L-1 ammonium formate. A chromatographic total run time of 13.0 min was achieved. The quantitation analysis was performed using multiple reaction monitoring （MRM） at the specificion transitions ofm/z 454.1[M-H]-→234.1for clevidipin; butyrate,,m/z 354.0[M-H]-→208.0forclevidipine acid andm/z256.1[M-H]-→227.1for elofesalamide （internal standard, IS） in the negative ionmode with electrospray ionization （ESI） source. The linear calibration curves for clevidipine butyrate andclevidipine acid were obtained in the concentration ranges of0.5和1 ng·m L-1The intra and inter- assay precisions were all below 12.9%, the accuracies were all in standard ranges. Stabilitytesting indicated that clevidipine butyrate and clevidipine acid in dog blood with the addition of denaturant methanol was stable under various processing and/or handling conditions. The validated method has been successfully applied to a pharmacokinetic study of clevidipine butyrate injection to 8 healthy Beagle dogs following intravenous infusion at a flow rate of （5 mg·h-1）
出处
《药学学报》
CAS
CSCD
北大核心
2015年第10期1290-1296,共7页
Acta Pharmaceutica Sinica
基金
国家自然科学基金青年科学基金资助项目(81503154)
