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目的建立动物血浆中马来酸氯苯那敏浓度的HPLC-MS分析方法,用以测定健康犬口服伪麻那敏渗透泵制剂后的血药浓度,估算受试制剂的药物动力学参数。方法血浆中加入甲醇-水(体积比为50︰50)和金刚烷胺内标溶液,混匀后经氢氧化钠碱化,用正己烷-二氯甲烷-异丙醇(体积比为2.0︰1.0︰0.1)提取,提取液氮气流吹干,残留物用流动相复溶,供分析用。色谱系统:Diamonsil C18柱(5μm,250 mm×4.6 mm);甲醇-水-甲酸(体积比为40︰60︰1)为流动相;流速:1.0 mL min-1;柱温:20℃。结果血浆中内源性物质对样品测定无干扰。马来酸氯苯那敏的线性为0.7~28.0μg·L-1,最低质量浓度为0.7μg·L-1,提取回收率为71.3%。日内、日间RSD均小于10.0%。测定6只比格犬口服受试制剂后的血药质量浓度经时过程,受试制剂及参比制剂的主要药物动力学参数分别为:t1/2=4.79 h;ρmax=5.95μg·L-1;tmax=4.83 h;AUC0-t=37.69μg·h·L-1。结论统计学表明受试制剂马来酸氯苯那敏具有渗透泵的特征。
OBJECTIVE: To establish HPLC-MS method for the determination of chlorphenamine maleate in animal plasma, and to determine the plasma concentration of Pseudarinam osmotic pump in healthy dogs and estimate the pharmacokinetic parameters of the tested formulations. Methods The plasma was added methanol - water (volume ratio of 50:50) and amantadine internal standard solution, after mixing alkalinized with sodium hydroxide, with n-hexane - dichloromethane - isopropanol (volume ratio of 2.0: 1.0: 0. 1) extraction, extraction liquid nitrogen flow drying, the residue was reconstituted with a mobile phase for analysis. Chromatography system: Diamonsil C18 column (5μm, 250 mm × 4.6 mm); methanol-water-formic acid (40︰60︰1 by volume) as mobile phase; flow rate: 1.0 mL min-1; Results The plasma endogenous substances did not interfere with the determination of the samples. The linearity of chlorpheniramine maleate was 0.7 ~ 28.0μg · L-1, the lowest concentration was 0.7μg · L-1, and the extraction recovery was 71.3%. Days, day RSD were less than 10.0%. The main pharmacokinetic parameters of the test preparation and the reference preparation were as follows: t1 / 2 = 4.79 h; ρmax = 5.95 μg · L- 1; tmax = 4.83 h; AUC0-t = 37.69 μg · h · L-1. Conclusions The statistics show that the chlorpheniramine maleate sample has the characteristics of osmotic pump.