摘要
利用超高效液相色谱-串联质谱(UPLC-MS/MS)的多反应监测(MRM)技术,结合多探针底物方法,对单酯型及双酯型乌头类生物碱组分对细胞色素P450(CYP450)亚型的活性影响进行了研究;同时利用超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-Q-TOF-MS/MS)对单酯型和双酯型乌头类生物碱组分在CYP450中的代谢指纹图谱进行了研究.活性影响研究结果表明,单酯型生物碱组分对CYP2C及2D的抑制能力较强,其IC50值分别为7.44和6.74μmol/L;双酯型生物碱组分对CYP1A2,3A,2C和2D均有较弱的抑制作用,其IC50值分别为39.48,70.44,17.36和86.04μmol/L.代谢指纹图谱显示,双酯型生物碱组分在大鼠肝微粒体中有6个特异性产物可以作为该反应的特征峰.
The effects of the components of monoester and diester diterpenoid alkaloids （ MDAs, DDAs） on the activities of hepatic microsomal CYP450 isozymes（CYP1A2, CYP2C, CYP2EI, CYP2D, CYP3A） were studied by ultra performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） combined with cocktail probe substrate＇s method. The metabolic fingerprints of MDAs and DDAs＇ components were studied in rat liver microsomes using UPLC-Q-TOF/MS/MS. The results showed that the components of MDAs had strong inhibitory effects on the activities of CYP2C and 2D, the ICso value was 7.44 and 6. 74 μmoL/L, respectively. The components of DDAs had weaker inhibitory effects on the activities of CYP1A2, 3A, 2C and 2D, the IC50 value was 39.48, 70. 44, 17.36 and 86. 04 μmoL/L, respectively. Six metabolites of DDAs in rat liver rnicrosomes were identified using UPLC-Q-TOF-MS/MS. They can be used as marked peaks for meta- bolic fingerprint of aconite alkaloids components.
出处
《高等学校化学学报》
SCIE
EI
CAS
CSCD
北大核心
2013年第9期2084-2089,共6页
Chemical Journal of Chinese Universities
基金
国家自然科学基金(批准号:81073040
81274046)
国家'九七三'计划项目(批准号:2011CB505300
2011CB505305)资助
关键词
乌头类生物碱
细胞色素P450
代谢指纹图谱
超高效液相色谱-串联质谱
多探针底物
Aconite alkaloid
Cytochrome P450
Metabolic fingerprint
Ultra performance liquid chromatog- raphy-tandem mass spectrometry（UPLC-MS/MS）
Cocktail probe substrate
