摘要
目的建立高效液相色谱-质谱/质谱联用法（HPLC-MS/MS）测定人血浆中丙戊酸镁的方法,并用于大鼠药动学研究。方法采用Shim-pack XR-ODS柱（3.0 mm×75 mm）,柱温25℃,流动相A为0.1%甲酸水溶液,B为甲醇,洗脱梯度为0-1.0 min 80%B,80%B平衡1.0-5.0 min;流速0.4 mL.min-1;用正离子电喷雾电离源,多反应方式检测,丙戊酸镁用于定量分析的离子对为m/z312.4→m/z102.2。血浆样品用甲醇沉淀蛋白后进样。结果丙戊酸镁在6.25-4 000 ng.mL-1线性关系良好,相关系数为0.995 9,最低定量限为6.25 ng.mL^-1。加样回收率94.88%-97.62%,日内日间精密度RSD均小于12%。丙戊酸镁缓释片起效慢,作用力维持时间比丙戊酸镁片长。结论该方法分析速度快、操作简单、灵敏度高,适用于丙戊酸镁药动学研究。
OBJECTIVE To establish a HPLC-MS/MS method for the determination of magnesium valprote in rat plasma and to study the pharmacokinetics of magnesium valprote.METHODS The analytes were determined by HPLC-MS/MS method using Shim-pack XR-ODS column.The mobile phase was composed by 0.1% formic acid and methanol.The analysis was achieved with gradient elution and positive ion MRM detection of magnesium valprote（m/z 312.4→102.2）.The column temperature was at 25 ℃.The plasma was deproteinized with methanol directly.RESULTS The calibration curve was linear within 6.25-4 000 ng·mL-1（r=0.995 9）.The lower limit of quantitation was 6.25 ng·mL-1.The recovery was in the range of 94.88%-97.62%.The relative standard deviations for the intra-day and inter-day validation were less than 12%.The pharmacokinetic parameters were calculated as the follows： ρmax（2 608.33±83.86） ng·mL-1;tmax（7.00±1.73） h;t1/2（27.99±1.52） h;AUC0-96（97 858.06±4 157.10） ng·h·mL-1;AUC0-∞（108 733.06±6 598.60） ng·h·mL-1 of magnesium valprote in rats.CONCLUSION The method is simple,accurate,fast,sensitive and suitable for the pharmacokinetic study of magnesium valprote.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2011年第5期378-381,共4页
Chinese Pharmaceutical Journal
基金
国家科技部重大资助项目(2008ZXJ09014-010)
