- 學位論文
利用快速靈敏的LC-MS/MS方法測定CoQ10之代謝物
A Rapid and Sensitive LC-MS/MS Method for Determination of Metabolites of Coenzyme Q10
摘要
輔酶Q10(CoQ10)，又稱作泛醌(ubiquinone)，為粒線體合成ATP的電子傳遞鏈中重要的脂溶性因子，除此之外，CoQ10已被廣泛應用在治療心臟衰竭並有許多報告指出CoQ10對於其他的疾病與症狀具有有益的功效，例如抗發炎、抗氧化、抗腫瘤等效益，然而，由於CoQ10本身屬於脂溶性物質，能夠被生物體所吸收利用的含量極低而最後的尿中代謝物是環狀並帶有磷酸化短側鍊的結構，但與CoQ10同為脂溶性且結構相似的維生素K的尿中代謝物卻是與醣醛酸根和硫酸根所鍵結，因此本次實驗以synergi polar-RP管柱和4000QTrap利用LC-MS/MS以多重反應監測方法（MRM）分析大鼠口服CoQ10之後的尿液及糞便中代謝物並進行鑑定，共有8種代謝物被鑑定出來，分別是原型CoQ10、甲基化、雙甲基化、硫酸根鍵結、葡糖醛酸氧化鍵結、雙葡糖醛酸化鍵結、硫醇酸化鍵結與穀胱胺酸鍵結代謝物產生，並發現服用CoQ10可能能夠促進苯丙胺酸代謝排除。
並列摘要
Coenzyme Q10 (CoQ10), also called ubiquinone, an essential fat-soluble substance for electron transport chain in mitochondria for synthesis of ATP. In addition, CoQ10 is widely consumed as a good compound to treat heart failure and there are many reports suggest that CoQ10 exerts a beneficial effect on a broad spectrum of pathological conditions, such as anti-inflammatory, anti-oxidant and anti-tumor functions. However, being a lipophilic substance the absorption of CoQ10 is limit and its metabolites in urine showed contained the ring structure with a short side chain and were phosphorylated. Nevertheless, the structure of vitamin K similar to CoQ10, which major urinary metabolites were conjugated with glucuronide and sulfate, therefore, we use synergi polar-RP column and 4000QTrap for LC-MS/MS with multiple reaction monitoring (MRM) method to analyze serum and urine after oral administration rats in this study. The purpose of identify the metabolites of CoQ10. There were eight metabolites had been identified, such as unconjugated CoQ10, methylation, bis-methylation, sulfated, glucuronide-oxidation, bis-glucuronide, mercapturic acid synthesis and glutathione(GSH) reaction metabolites and we suggested CoQ10 maybe can promote the elimination of phenylalanine.