School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Department of Pharmacy, The Central Hospital of Yongzhou, Yongzhou, 425000, China.
Anal Biochem. 2022 Mar 1;640:114407. doi: 10.1016/j.ab.2021.114407. Epub 2021 Oct 9.
Toddalia asiatica L., a significant medicinal plant in the family Rutaceae, has been applied to treat rheumatoid diseases for decades. Its pharmacological activities are mainly attributed to the existence of generous coumarins and alkaloids; however, the pharmacokinetics of Toddalia asiatica L. remain unclear. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established for the simultaneous determination of four coumarins, three alkaloids and one flavonoid (hesperidin, nitidine chloride, chelerythrine, toddalolactone, isopimpinellin, pimpinellin, bergapten and dictamnine) in rat feces as well as four coumarins and one alkaloid (toddalolactone, isopimpinellin, pimpinellin, bergapten and dictamnine) in rat plasma and urine. Chromatographic separation was accomplished on an Agilent ZORBAX SB-C18 column (2.1 × 150 mm, 5 μm) with acetonitrile (containing 0.1% formic acid) and 5 mmol/L aqueous ammonium formate for gradient elution. A correlation coefficient greater than 0.9925 reflected the excellent linearity of the analytical response. The lower limits of quantification were 30.0, 10.0, 10.0, 30.0, 5.0, 10.0, 2.5 and 2.5 ng/mL for hesperidin, nitidine chloride, chelerythrine, toddalolactone, isopimpinellin, pimpinellin, bergapten and dictamnine, respectively. The intra- and inter-day precision were less than 12.7%, and the accuracy was between -11.8% and 12.9%. In summary, this study is the first to study the pharmacokinetics and excretion of T. asiatica extract after oral administration, which may provide a scientific basis for its clinical applications.
托地利亚 Asiatica L.，一种在 Rutaceae 科中具有重要药用价值的植物，已被应用于治疗类风湿性疾病数十年。其药理学活性主要归因于丰富的香豆素和生物碱的存在；然而，托地利亚 Asiatica L. 的药代动力学仍不清楚。建立了一种高效液相色谱-串联质谱法（HPLC-MS/MS），用于同时测定大鼠粪便中的四种香豆素、三种生物碱和一种类黄酮（橙皮苷、氯化两面针碱、白屈菜红碱、托地洛内酯、异欧前胡素、茴芹素、补骨脂素和白鲜碱）以及大鼠血浆和尿液中的四种香豆素和一种生物碱（托地洛内酯、异欧前胡素、茴芹素、补骨脂素和白鲜碱）。色谱分离在 Agilent ZORBAX SB-C18 柱（2.1×150mm，5μm）上进行，采用乙腈（含 0.1%甲酸）和 5mmol/L 水合甲酸铵进行梯度洗脱。分析响应的相关系数大于 0.9925，表明具有良好的线性。橙皮苷、氯化两面针碱、白屈菜红碱、托地洛内酯、异欧前胡素、茴芹素、补骨脂素和白鲜碱的定量下限分别为 30.0、10.0、10.0、30.0、5.0、10.0、2.5 和 2.5ng/mL。日内和日间精密度均小于 12.7%，准确度在-11.8%至 12.9%之间。总之，本研究首次研究了口服托地利亚 Asiatica 提取物的药代动力学和排泄情况，这可能为其临床应用提供科学依据。
