【摘要】 利用高效液相色谱分离、电喷雾-线性离子阱质谱法(LC-ESI/LTQ)、电喷雾-离子阱/飞行时间串联质谱法(LC-ESI/IT-TOF)鉴定鸡血浆中乙酰甲喹及其代谢物的结构。分别采用Hypersil Gold和Symmetry ShieldTM色谱柱,以含有0.01%甲酸水溶液(A)和甲醇(B)为流动相,梯度洗脱,电喷雾离子源(ESI)正离子模式进行检测。鸡口服给药乙酰甲喹(20mg/kg)后,翅下静脉采血,待分析血浆用乙腈-乙酸乙酯(3:2,V/V)混合液提取,吹干。残渣用30%甲醇水溶液复溶,上机检测。用Shimadzu′s Composition分子预测软件推测分子离子及其子离子质量,Xcalibur2.0.7软件分析线性离子阱质谱仪测得质谱图。鉴定出5种主要代谢物,分别为3-甲基-2-(1-羟基)乙基-喹啉-N1,N4-二氧化物(M1)、3-甲基-2-(1-羟基)乙基-喹啉-N4-一氧化物(M2)、3-甲基-2-乙酰基-喹啉-N4-一氧化物(M3)、3-甲基-2-乙酰基-喹啉(M4)和3-羟甲基-2-(1-羟基)乙基-喹啉-N1,N4-二氧化物(M5)。同时根据推测结果对代谢物M1～M4进行化学合成,利用合成代谢物的谱学测定数据进一步确证推测代谢物的化学结构。本实验为研究乙酰甲喹体内代谢产物及代谢机理提供了便捷而有效的模式。更多还原

【Abstract】 The chemical structures of mequindox related metabolites in chicken plasma had been investigated using high performance liquid chromatography combined with linear ion trap quadrupole(LC-ESI/LTQ) and high performance liquid chromatography combined with ion trap-time of flight-mass spectrometry(LC-ESI/ITTOF).Samples were separated by Hypersil BDS C18 and symmetry ShieldTM columns,respectively,and 0.01% formic acid aqueous(A) and methanol(B) were used as mobile phase with gradient elution.Electrospray ionization mass spectrometric(ESI) source was used and operated in positive ion mode.When chickens were orally administered with mequindox at dosage of 20 mg/kg,blood samples were collected from the brachial vein.Mequindox and its metabolites were extracted by the mixture of acetonitrile and acetoacetate(3:2,V/V).After solvent evaporated,the residue was dissolved in 30% methanol aqueous and the solution was detected by LC/IT-TOF MS and LC-ESI/LTQ.The molecule weight from LC-ESI/IT-TOF was analyzed by software Shimadzu’s Composition and the mass chromatogram from LC-ESI/LTQ was analyzed by software Xcalibur 2.0.7.According to the molecular weight and MSn data,referring the metabolic reaction rules,five chemical structures of mequindox related metabolites in chicken plasma were identified.Metabolites(M1-M4) were synthesized to verify the structure of metabolites.The metabolites are 3-methyl-2-(1-hydroxy)ethyl-quinoxaline-N1,N4-dioxide(M1),3-methyl-2-(1-hydroxy) ethyl-quinoxaline-N4-oxide(M2),3-methyl-2-acetylquinoxaline-N4-oxide,3-methyl-2-acetyl-quinoxaline (M4),3-hydroxymethyl-2-(1-hydroxy) ethyl-quinoxaline-N1,N4-dioxide(M5).更多还原