Aim To develop and validate a liquid chromatography-tandem mass spectrometric（LC/MS/MS） method for the simultaneous quantification of ephedrine and chlorpheniramine in human plasma after oral administration of a com...Aim To develop and validate a liquid chromatography-tandem mass spectrometric（LC/MS/MS） method for the simultaneous quantification of ephedrine and chlorpheniramine in human plasma after oral administration of a compound preparation.Methods The analytes and the internal standard,diphenhydramine,were isolated from plasma by protein precipitation with methanol,then chromatographied on a Zorbax SB-C18 column（150 mm×4.6 mm ID） using a mobile phase consisted of methanol-water-formic acid（80∶20∶0.5,v/v）,at a flow rate of 0.5 mL·min-1.A tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode.Selected reaction monitoring（SRM） using the precursor to produce ion combinations of m/z 166→115,（m/z） 275→230 and m/z 256→167 were used to quantify ephedrine,chlorpheniramine and the internal standard,respectively.Results The linear concentration ranges of the calibration curves for ephedrine and chlorpheniramine were 0.50-200 μg·L-1 and 0.050-20.0 μg·L-1,respectively.The lower limits of quantification were 0.50 μg·L-1 for ephedrine and 0.050 μg·L-1 for chlorpheniramine,individually.The intra-and inter-day relative standard deviation（RSD） across three validation runs over the entire concentration range was less than 9.3% for both ephedrine and chlorpheniramine.The inter-day accuracy（RE） was within ±3.4% for the analytes.Each sample was chromatographied within 3.3 min.The method was successfully used in pharmacokinetics study of ephedrine and chlorpheniramine in human plasma after oral administration of a compound preparation containing 5 mg ephedrine hydrochloride,1 mg chlorpheniramine maleate,50 mg phenytoin,12.5 mg theophylline,12.5 mg theobromine and 7.5 mg caffeine.No interaction among the six components was observed on their pharmacokinetic parameters.Conclusion The method was proved to be highly sensitive,selective,and suitable for pharmacokinetics investigations of different compound preparations cont展开更多
采用液相串联质谱方法开发并验证了一种用于测定大鼠血浆中多奈哌齐的方法,并将方法应用于多奈哌齐双层微球在大鼠体内的药代动力学评价。使用氯苯那敏作为内标,用乙腈沉淀蛋白质后,在ZORBAX Eclipse Plus C_(18)上分离目标分析物,按体...采用液相串联质谱方法开发并验证了一种用于测定大鼠血浆中多奈哌齐的方法,并将方法应用于多奈哌齐双层微球在大鼠体内的药代动力学评价。使用氯苯那敏作为内标,用乙腈沉淀蛋白质后,在ZORBAX Eclipse Plus C_(18)上分离目标分析物,按体积比40∶60,流动相采用0.1%甲酸溶液与乙腈进行等度洗脱。质谱分析采用电喷离子源-正离子模式联合多反应监测分析,分别监测多奈哌齐和氯苯那敏的离子对m/z 380.0→243.0和m/z 275.0→230.0的转变。多奈哌齐的浓度范围为3.75~120.00 ng/mL,r^(2)大于0.999。准确度误差和相对标准偏差均低于15%。基质效应变异系数分别为3.15%、2.96%和1.36%。不同条件下多奈哌齐稳定变异系数在0.27%~1.61%之间。多奈哌齐双层微球在大鼠体内的释药行为,吸收迅速,消除过程缓慢,表现出良好的药物缓释特性。开发了新的液相串联质谱方法,这种方法具有高特异性和灵敏度,并且快速可靠。为多奈哌齐双层微球的体内释药行为提供有效的评价工具,为多奈哌齐双层微球的开发和临床应用提供了重要的科学依据。展开更多
文摘Aim To develop and validate a liquid chromatography-tandem mass spectrometric（LC/MS/MS） method for the simultaneous quantification of ephedrine and chlorpheniramine in human plasma after oral administration of a compound preparation.Methods The analytes and the internal standard,diphenhydramine,were isolated from plasma by protein precipitation with methanol,then chromatographied on a Zorbax SB-C18 column（150 mm×4.6 mm ID） using a mobile phase consisted of methanol-water-formic acid（80∶20∶0.5,v/v）,at a flow rate of 0.5 mL·min-1.A tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode.Selected reaction monitoring（SRM） using the precursor to produce ion combinations of m/z 166→115,（m/z） 275→230 and m/z 256→167 were used to quantify ephedrine,chlorpheniramine and the internal standard,respectively.Results The linear concentration ranges of the calibration curves for ephedrine and chlorpheniramine were 0.50-200 μg·L-1 and 0.050-20.0 μg·L-1,respectively.The lower limits of quantification were 0.50 μg·L-1 for ephedrine and 0.050 μg·L-1 for chlorpheniramine,individually.The intra-and inter-day relative standard deviation（RSD） across three validation runs over the entire concentration range was less than 9.3% for both ephedrine and chlorpheniramine.The inter-day accuracy（RE） was within ±3.4% for the analytes.Each sample was chromatographied within 3.3 min.The method was successfully used in pharmacokinetics study of ephedrine and chlorpheniramine in human plasma after oral administration of a compound preparation containing 5 mg ephedrine hydrochloride,1 mg chlorpheniramine maleate,50 mg phenytoin,12.5 mg theophylline,12.5 mg theobromine and 7.5 mg caffeine.No interaction among the six components was observed on their pharmacokinetic parameters.Conclusion The method was proved to be highly sensitive,selective,and suitable for pharmacokinetics investigations of different compound preparations cont
