Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Curr Drug Metab. 2021;22(1):70-82. doi: 10.2174/1389200221666201217154219.
Alpiniae oxyphyllae Fructus (AOF), a traditional Chinese medicine (TCM), is widely used in the treatment of urinary, gastrointestinal and neurologic diseases in China. Although terpenoids are the main active ingredients of AOF, there are few researches on their pharmacokinetics and metabolism.
In this study, a sensitive, rapid, accurate and novel ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to evaluate the pharmacokinetic behavior of five terpenoids (oxyphyllenodiol B, (4S*,5E,10R*)-7-oxo-tri-nor-eudesm-5-en-4β-ol, 7-epi-teucrenone, (+)- (4R,5S,7R)-13-hydroxynootkatone, (E)-labda-12,14-dien-15(16)-olide-17-oic acid) in rats after oral administration of AOF extracts. 27 metabolic metabolites of the five terpenoids were identified by ultra high performance liquid chromatography -Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) based on precise mass and fragment ions.
The established pharmacokinetic analysis method showed good linearity over a wide concentration range, and the lower quantitative limit (LLOQ) ranged from 0.97 to 4.25 ng/mL. Other validation parameters were within the acceptable range. In addition, 27 metabolites were identified in plasma, urine and feces samples, and the metabolic pathways of five terpenoids were mainly focused on glucoside conjugation, dehydration, desaturation and glycine conjugation.
This is the first study on the pharmacokinetics and metabolism of five terpenoids in AOF, illuminating the disposal process of terpenoids in vivo. It was expected that the results of this study would provide some references for the apprehension of the action mechanism and the further pharmacological study of five terpenoids in AOF.
益智果实（AOF）是一种传统中药（TCM），在中国被广泛用于治疗泌尿系统、胃肠道和神经系统疾病。尽管萜类化合物是 AOF 的主要活性成分，但对其药代动力学和代谢的研究较少。
本研究建立了一种灵敏、快速、准确、新颖的超高效液相色谱串联质谱（UPLC-MS/MS）方法，用于评估益智提取物中五种萜类化合物（氧化益智二醇 B、（4S*，5E，10R*）-7-氧-三-nor-eudesm-5-烯-4β-醇、7-表-teucrenone、（+）-（4R，5S，7R）-13-羟基诺卡酮、（E）-labda-12,14-二烯-15（16）-内酯-17-酸）在大鼠体内的药代动力学行为。基于精确质量和碎片离子，采用超高效液相色谱- Q Exactive 混合四极杆轨道阱高分辨率精确质量质谱（UHPLC-Q-Orbitrap HRMS）鉴定了这五种萜类化合物的 27 种代谢产物。
所建立的药代动力学分析方法在较宽的浓度范围内表现出良好的线性，定量下限（LLOQ）范围为 0.97 至 4.25ng/mL。其他验证参数均在可接受范围内。此外，在血浆、尿液和粪便样品中鉴定出 27 种代谢产物，五种萜类化合物的代谢途径主要集中在糖苷结合、脱水、去饱和和甘氨酸结合上。
这是首次对 AOF 中五种萜类化合物的药代动力学和代谢进行研究，阐明了萜类化合物在体内的处置过程。预计本研究结果将为进一步了解 AOF 中五种萜类化合物的作用机制和药理学研究提供一些参考。
