李海龙,龚晶雯,文琪,程守前,罗喻超,张俊清,谭银丰
LI Hailong,GONG Jingwen,WEN Qi,CHENG Shouqian,LUO Yuchao,ZHANG Junqing,TAN Yinfeng

• 1:海南医学院海南省热带药用植物研究开发重点实验室

摘要(Abstract)：

目的建立快速、灵敏测定大鼠血浆中5-羟基-1,7-双苯-3-庚酮(DPHC,5-Hydroxy-1,7-diphenyl-3-heptanone)的LC-MS/MS方法,并应用于药动学研究。方法血浆样品经叔丁基甲醚萃取后进行分析,采用Kinetex XB-C_(18)色谱柱(2.10 mm×50mm,2.6μm),柱温40℃,以水(含0.01%甲酸)—甲醇(含0.01%甲酸)为流动相梯度洗脱,流速0.30 m L·min~(-1),ESI离子源,多反应离子监测(MRM),用于定量分析的离子对为m/z 283.3→265.1,内标化合物益智酮甲为313.1→137.0。结果 DPHC的线性范围为2.0~2 000.0 ng·mL~(-1)(r=0.995 7),最低定量限为2.0 ng·mL~(-1);提取回收率为75.62%~77.75%,基质效应为85.21%~90.24%;日内和日间精密度RSD均<15%。口服(po.)和静脉注射(iv.)DPHC主要药代动力学参数:C_(max)分别为(61.2±28.8),(246.7±6.7)ng·mL~(-1);t_(1/2)分别为(1.90±0.68),(0.34±0.20)h;AUC0-t分别为(100.4±33.8),(78.1±1.8)h·ng·mL~(-1)。结论本法经方法学验证,适用于大鼠血浆中DPHC浓度的测定,适合药动学研究。
OBJECTIVE To develop a rapid sensitive LC-MS/MS method for determination of 5-Hydroxy-1,7-diphenyl-3-heptanone( DPHC) in rat plasma,and apply the method in pharmacokinetics study furtherly. METHODS The plasma samples were extracted by methyl tert-butyl ether( MTBE). The chromatographic analysis was carried out by Kinetex XB-C_(18)column( 2. 10 mm× 50 mm,2.6 μm) and the column temperature was 40 ℃. The mobile phase consisted of water( contain 0. 01% formic acid) and methanol( contain 0.01% formic acid) with gradient elution at a flow rate of 0.3 m L·min~(-1).Electrospray ionization( ESI) with a positive-ion and multiple reaction monitoring mode( MRM) was adopted. Yakucinone A was used as the internal standard,the precursor ion → product ion transitions m/z 283.3 →265.1 for DPHC and m/z 313.1 →137.0 for internal standard were monitored. RESULTS The plasma standard curve of DPHC were linear in the range of 2.0 ~ 2 000.0 ng·mL~(-1)( r= 0.995 7).The limit of quantification was 2.0 ng·mL~(-1).The plasma extraction recovery of DPHC was 75.62% ~ 77.75%.Matrix effect were 85.21% ~ 90.24%.The intra-day and inter-day RSDs were less than 15%. The main pharmacokinetic parameters of po. and iv. were as follows: C_(max)were( 61. 2 ± 28. 8),( 246. 7 ± 6. 7) ng·mL~(-1)respectively; t_(1/2)were( 1.90± 0. 68),( 0. 34 ± 0. 20) h respectively; AUC_(0-1) twere( 100. 4 ± 33. 8),( 78. 1 ± 1. 8) h·ng·mL~(-1)respectively.CONCLUSION The established method is proved to be suitable for determination of DPHC in rat plasma,it can be used as an effective method for the pharmacokinetics studies.

关键词(KeyWords)： 5-羟基-1,7-双苯-3-庚酮;血药浓度;基质效应;药动学;方法验证;液相色谱串联质谱法
5-Hydroxy-1,7-diphenyl-3-heptanone;plasma drug concentration;matrix effect;pharmacokinetics;methods validation;LC-MS/MS

Abstract:

Keywords:

基金项目(Foundation): 海南省中药现代化专项(2015ZY06);; 国家自然科学基金项目(81560721)

作者(Author): 李海龙,龚晶雯,文琪,程守前,罗喻超,张俊清,谭银丰
LI Hailong,GONG Jingwen,WEN Qi,CHENG Shouqian,LUO Yuchao,ZHANG Junqing,TAN Yinfeng

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