摘要
目的采用高效液相-串联质谱方法测定血浆褪黑素的药物浓度。方法血浆样本经乙酸乙酯提取后,上清液经真空浓缩仪浓缩吹干,残留样本使用流动相[0.1%甲酸水溶液-甲醇(56∶44)]溶解,高速离心后取上清液进样,样本经Xterra~RP_(18)(4.6 mm×100 mm,3.5μm)色谱柱分离后由电喷雾离子源正离子化后,通过三重四极杆串联质谱仪,在多反应监测模式下对褪黑素(m/z 233.1→174.1)和内标褪黑素-D7(m/z 240.2→178.0)的浓度进行测定。结果褪黑素的血浆浓度在0.020 00~30.00 ng·m L^(-1)内线性良好,定量下限为0.020 00 ng·m L^(-1),批内、批间精密度<15%,提取回收率为59.0%~65.0%,基质效应为95.5%~98.9%,变异小于15%。结论该分析方法简便、灵敏、准确,适用于褪黑素缓释片人体药动学研究。
OBJECTIVE To establish an HPLC-MS/MS method for the determination of melatonin in human plasma. METH- ODS The plasma samples were extracted with ethyl acetate, using melatonin-D7 as the internal standard （IS）. Then the ethyl acetate layer was evaporated in vacuum concentrator. Dried samples were redissolved in mobile phase （0. 1% formic acid-methanol = 56： 44, V/V）, vortexed and centrifuged. The redissolved solution was transferred to an auto sampler vial and the supernatant was injected to the HPLC-MS/MS system. The MS/MS analysis was carried out in positive ionization mode by multiple reactions monitoring （MRM） at m/z 233.1→174. 1 for melatonin and m/z 240. 2→178. 0 for IS, respectively. RESULTS The calibration curve of melatonin in hu- man plasma was linear over the concentration range of 0. 020 00 - 30. 00 ng · mL- 1. The lower limit of quantitation was 0. 020 00 ng · mL- 1. The RSDs of within-day and between-day were less than 15%. The extraction recoveries were between 59. 0% -65. 0%. The matrix effects were between 95.5% -98. 9%. CONCLUSION The method is proved to be convenient, sensitive and accurate. It can be applied to study the pharmacokinetics of melatonin prolonged-release tablets in healthy Chinese volunteers.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2016年第9期737-741,共5页
Chinese Pharmaceutical Journal
