Abstract
本文建立了一种基于液相色谱-电喷雾离子阱质谱(LC-ESI-ITMS)技术和“N in 1”模式的药物及其代谢物快速高通量分离与鉴定方法. 该方法首先利用体外代谢方法得到肝微粒体中药物与各自代谢产物混合体系, 然后采用“N in 1”模式对该混合体系进行处理, 并利用 LC-ESI-ITMS 联用技术对各待测药物及其代谢物进行分析, 得到药物和代谢物的分子量信息, 进一步结合多级串联质谱(LC-MSn)分析结果获得结构信息, 对代谢物进行鉴定, 从而快速的推测代谢物结构, 进而得到药物的生物转化规律. 本方法用于6种药物及其4种代谢物的分析, 实验结果表明: 该方法具有快速、高效、灵敏, 选择性好等特点。
A high-throughput analysis method applying liquid chromatography-electrospray ionization-ion trap mass spectrometry (LC-ESI-ITMS) for the simultaneous quantitative analysis of drug candidates and their in-vitro metabolites is described. The drugs were individually incubated with mouse liver microsome S9 fraction. The incubation samples were pooled together for the “N in 1” analysis by LC-ESI-ITMS in full-scan mode. The drugs and their metabolites were identified from the determination of molecular ions. The metabolite detection was confirmed from tandem mass spectrometry (MSn) analysis. In addition, the metabolic stability of drugs was determined by comparing the peak intensities between the control and incubated samples. This analytical approach was applied for analysis of 6 drugs and 4 major metabolites. The obtained results indicated that the method could provide significant increase in analytical throughput.
A high-throughput analysis method applying liquid chromatography-electrospray ionization-ion trap mass spectrometry (LC-ESI-ITMS) for the simultaneous quantitative analysis of drug candidates and their in-vitro metabolites is described. The drugs were individually incubated with mouse liver microsome S9 fraction. The incubation samples were pooled together for the “N in 1” analysis by LC-ESI-ITMS in full-scan mode. The drugs and their metabolites were identified from the determination of molecular ions. The metabolite detection was confirmed from tandem mass spectrometry (MSn) analysis. In addition, the metabolic stability of drugs was determined by comparing the peak intensities between the control and incubated samples. This analytical approach was applied for analysis of 6 drugs and 4 major metabolites. The obtained results indicated that the method could provide significant increase in analytical throughput.
| Translated title of the contribution | Simultaneous quantitative “N in 1” analysis of drugs and their metabolites by liquid chromatography-electrospray ion trap mass spectrometry |
|---|---|
| Original language | Chinese (Simplified) |
| Pages (from-to) | 757-761 |
| Number of pages | 5 |
| Journal | 中国科学: 化学 |
| Volume | 40 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2010 |
User-Defined Keywords
- 液相色谱-电喷雾离 子阱质谱
- 肝微粒体
- 药物
- 体外代谢
- "N in 1"
- liquid chromatography-electrospray ion trap mass spectrometry
- mouse liver S9 fractions
- drug
- in-vitro metabolism