Determination of pyrrolizidine alkaloid metabolites from mouse liver microsomes using tandem mass spectrometry and gas chromatography/mass spectrometry.
Determination of pyrrolizidine alkaloid metabolites from mouse liver microsomes using tandem mass spectrometry and gas chromatography/mass spectrometry.
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DOI：
10.1016/0378-8741(88)90098-0
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发表时间：
1988-03
期刊：
影响因子：
--
通讯作者：
CK Winter;HJ Segall;AD Jones
中科院分区：
文献类型：
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作者：
CK Winter;HJ Segall;AD Jones
采用串联质谱仪(MS/MS)和气相色谱/质谱仪(GC/MS)对重要的吡咯里西定生物碱代谢物进行了快速、灵敏的鉴定和定量。通过比较小鼠肝微体提取液中特定离子的碰撞活化分解/质量分析离子动能谱与可疑代谢物的合成标准谱，完成了对小鼠肝微体提取液中吡咯里西定生物碱千里光碱和野百合碱的氮氧化物和水解性代谢物的鉴定。用三甲基硅烷(TMS)衍生物的GC/MS检测到微量有毒代谢物二氢吡咯烷(DHP)，但肝微粒体提取物中DHP的含量低于MS/MS的检测限。用快原子轰击MS/MS法定量测定了提取物中N-氧化物的含量，其他物质对N-氧化物的抑制作用很小。用毛细管气相色谱/质谱法对代谢物陈酸、野百合酸和DHP的TMS衍生物进行了定量。研究结果表明，吡咯里西丁生物碱代谢的三个主要途径(N-氧化、水解和氧化)对吡咯类化合物的相对贡献可以使用单一的分析仪器和最小的样品制备来评估。
The rapid and sensitive identification and quantification of important pyrrolizidine alkaloid metabolites using tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GC/MS) is described. Identifications ofN‐oxide and hydrolytic metabolites of the pyrrolizidine alkaloids senecionine and monocrotaline in extracts of mouse hepatic microsomal incubations were accomplished by comparing collisionally activated decomposition/mass‐analyzed ion kinetic energy spectra of specific ions from microsomal extracts with spectra obtained from synthetic standards of suspected metabolites. Trace amounts of the toxic metabolite dihydropyrrolizine (DHP) were observed by GC/MS of trimethylsilyl (TMS) derivatives, but the amounts present in hepatic microsomal extracts were below the MS/MS limit of detection. Quantitative determinations of senecionineN‐oxide were performed by fast atom bombardment MS/MS. Suppression ofN‐oxide ionization by other substances in the extracts was judged to be minimal. The TMS derivatives of the metabolites senecic acid, monocrotalic acid and DHP were quantified using capillary GC/MS. Results from the study demonstrate that the relative contributions of the three major pathways of pyrrolizidine alkaloid metabolism (N‐oxidation, hydrolysis and oxidation to pyrrolic compounds) can be assessed using a single analytical instrument and minimal sample preparation.