Identification of in vivo liver metabolites of Δ1 ‐tetrahydrocannabinol, cannabidiol, and cannabinol produced by the guinea‐pig
Identification of in vivo liver metabolites of Δ1 ‐tetrahydrocannabinol, cannabidiol, and cannabinol produced by the guinea‐pig
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豚鼠产生的 Δ1-四氢大麻酚、大麻二酚和大麻酚的体内肝脏代谢物的鉴定
DOI：
10.1111/j.2042-7158.1980.tb12910.x
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发表时间：
1980
影响因子：
3.3
通讯作者：
W. D. Paton
中科院分区：
文献类型：
--
作者：
D. Harvey;B. Martin;W. D. Paton
采用气相色谱-液相色谱-质谱联用技术研究了豚鼠体内产生的Δ1‐四氢大麻酚（Δ1‐THC）、大麻二酚（CBD）和大麻酚（CBN）的代谢物。鉴定出45种Δ1‐THC代谢物，其中12种以前未报道过。检测到其他几种代谢物，但未确定。主要的代谢途径包括烯丙基和脂肪羟基化，氧化成酮和酸，侧链可能通过β氧化途径氧化降解，以及葡萄糖醛酸缀合物的形成。二代和三代代谢物丰富。代谢与小鼠和大鼠的代谢有很大不同，1″‐和6β‐羟基化和侧链的氧化降解是主要的代谢途径。1″‐Hydroxy‐Δ1‐THC被发现为一对异位异构体。与CBD相似的代谢途径；鉴定出20种代谢物，其中2种为新代谢物。仅鉴定出6种CBN代谢物。这些主要是单取代的位置与Δ1‐THC和CBD相同。
The metabolites of Δ1 ‐trahydrocannabinol (Δ1 ‐THC), cannabidiol (CBD), and cannabinol (CBN) produced in vivo by the guinea‐pig have been studied by combined gas‐liquid chromatography‐mass spectrometry. 45 metabolites of Δ1 ‐THC were identified of which 12 have not been reported before. Several other metabolites were detected but not identified. The major metabolic routes involved allylic and aliphatic hydroxylations, oxidations to ketones and acids, oxidative degradation of the side‐chain presumably by the β‐oxidation pathway, and formation of glucuronide conjugates. Di‐ and tri‐substituted metabolites were abundant. The metabolism differed considerably from that observed in mouse and rat in that 1″‐ and 6β‐hydroxylation and oxidative degradation of the side‐chain were major metabolic pathways. 1″‐Hydroxy‐Δ1 ‐THC was found as a pair of diasteroisomers. Similar metabolic pathways were observed with CBD; twenty metabolites were identified of which two were new. Only 6 metabolites of CBN were identified. These were mainly mono‐substituted in the same positions as were observed with Δ1 ‐THC and CBD.