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目的建立一种LC-MS/MS法,测定Beagle犬血浆中可乐定的质量浓度,从而对盐酸可乐定缓释片在犬体内的药物动力学行为进行研究。方法采用液-液萃取法制备血浆样品;色谱柱:Luna C_(18)柱,采用梯度洗脱方式,流动相:A为甲醇(含体积分数为0.3%的甲酸溶液),B为5 mmol·L~(-1)醋酸铵缓冲溶液(含体积分数为0.3%的甲酸溶液);采用多反应监测扫描方式,测定Beagle犬口服给予盐酸可乐定缓释片后血浆中可乐定的质量浓度。结果 Beagle犬血浆中可乐定的质量浓度在25~1 000 ng·L~(-1)内线性关系良好,相关系数r=0.998 6;日内和日间精密度不大于13.2%;犬血浆样品中可乐定的提取回收率在76.0%~82.3%内,基质效应在100.3%~112.0%内。结论该方法适合于犬体内可乐定的药物动力学的研究。
OBJECTIVE To establish a LC-MS / MS method for the determination of clonidine in Beagle dogs plasma, and to study the pharmacokinetics of clonidine hydrochloride sustained-release tablets in dogs. Methods The plasma samples were prepared by liquid-liquid extraction. The column was eluted by gradient elution on a Luna C 18 column. The mobile phase consisted of methanol (containing 0.3% by volume formic acid) and B 5 mmol (-1) ammonium acetate buffer solution (containing 0.3% by volume of formic acid solution). The plasma concentration of clonidine in Beagle dogs was determined by multi-reaction monitoring and scanning method after oral administration of clonidine hydrochloride sustained-release tablets. Results The plasma concentration of clonidine in Beagle dogs was linear in the range of 25-1 000 ng · L -1 with a correlation coefficient of 0.998 6. The intra- and inter-day precision was no more than 13.2% The recoveries of clonidine ranged from 76.0% to 82.3%, and the matrix effects ranged from 100.3% to 112.0%. Conclusion This method is suitable for the study of pharmacokinetics of clonidine in dogs.