阿普洛尔在犬、豚鼠和大鼠肝微粒体中的生物转化。

Biotransformation of alprenolol in dog, guinea-pig and rat liver microsomes.

Hoffmann K J, Skånberg I, Borg K O

Xenobiotica. 1979 Feb;9(2):79-91. doi: 10.3109/00498257909038709.

Abstract

Metabolites of alprenolol were isolated and identified in dog, guinea-pig and rat liver microsomes by means of g.l.c.-mass spectrometry and comparison with synthetic reference compounds. 2. The compounds were chromatographed as n-butylboronate derivatives, giving a series of diagnostic ions in the mass spectral fragmentation, which was elucidated by using stable isotopes. 3. Alprenolol was metabolized by aromatic ring hydroxylation, oxidation of the allylic function, and degradation of the isopropylaminopropanol side-chain. Alprenolol and four metabolites were quantified by h.p.l.c. and batch extraction techniques based on radioactivity measurements. 4. Five metabolites were detected in rat and guinea-pig liver microsomes and four in the dog. A species variation in the biotransformation of the allyl function in alprenolol was observed. The metabolite formed by oxidation of the allyl double bond was detected in significant amounts in the guinea-pig, and was also formed in the rat but could not be detected in dog liver microsomes.

摘要

通过气相色谱-质谱联用技术，并与合成参考化合物进行比较，在狗、豚鼠和大鼠肝脏微粒体中分离并鉴定了烯丙洛尔的代谢产物。2. 这些化合物以硼酸正丁酯衍生物的形式进行色谱分析，在质谱裂解过程中产生一系列诊断离子，通过使用稳定同位素对其进行了阐明。3. 烯丙洛尔通过芳香环羟基化、烯丙基官能团氧化以及异丙基氨基丙醇侧链降解进行代谢。烯丙洛尔和四种代谢产物通过高效液相色谱法和基于放射性测量的批量提取技术进行定量。4. 在大鼠和豚鼠肝脏微粒体中检测到五种代谢产物，在狗中检测到四种。观察到烯丙洛尔中烯丙基官能团生物转化的种属差异。在豚鼠中大量检测到由烯丙基双键氧化形成的代谢产物，在大鼠中也有形成，但在狗肝脏微粒体中未检测到。