Supercritical Fluid Carbon Dioxide Extraction Of Total Alkaloids From Sophora Moorcroftiana And Its Pharmacokinetics In Normal Rats

Objective: To extract total alkaloids from Sophora moorcroftiana seeds using supercritical fluid CO₂ extraction technology and optimize the process,and to investigate the pharmacokinetics of Sophora moorcroftiana seed extract in normal SD rats.Methods: Firstly,the single-factor experiment of supercritical fluid CO₂ extraction of total alkaloids from Sophora moorcroftiana seeds was carried out to determine the factors affecting the content of total alkaloids in Sophora moorcroftiana seeds.Then,according to the results of the single-factor experiment,Box-Behnken response surface methodology experiment was designed to determine the optimal extraction conditions for total alkaloids from Sophora moorcroftiana seeds using supercritical fluid CO₂ extraction technology.Finally,an ultra-performance liquid chromatography-mass spectrometry（UPLC-MS）method was developed for the determination of total alkaloid content in Sophora moorcroftiana seeds,which was used to investigate the pharmacokinetics of Sophora moorcroftiana seed extract in normal rats.Results: When the extraction pressure was 31 MPa,the extraction temperature was 70 ℃ and the extraction time was 162.18 min,the content of total alkaloids extracted from Sophora moorcroftiana seeds was the highest,and 68.88 μg total alkaloids could be extracted from 1 g Sophora moorcroftiana seeds.The RSD of precision and stability of the established methodology were both less than 15%,with high specificity and no interference of endogenous substances.Among the four extracts of total alkaloids from Sophora moorcroftiana,the pharmacokinetic parameters were t1/2（5.331 ± 0.868）h,AUC（0-t）（3797.529 ± 615.886）mg/L * h,Cmax（381.197 ± 29.507）mg/L and Tmax（5.500 ± 2.598）h in matrine,t1/2（3.819 ± 6.614）h,AUC（0-t）（3.362 ±1.694）mg/L * h,Cmax（2.283 ± 1.018）mg/L and Tmax（1.393 ± 1.265）h in oxymatrine,t1/2（2.642 ± 1.153）h,AUC（0-t）（348.957 ± 72.158）mg/L * h,Cmax（42.191 ± 11.767）mg/L and Tmax（5.000 ± 3.202）h in sophocarpine,and t1/2（6.023 ± 1.384）h,AUC（0-t）（1312.383 ± 116.847）mg/L * h,Cmax（134.587 ± 20.390）mg/L and Tmax（6.000 ± 1.155）h in sophoridine,respectively.Conclusion: Single-factor experiment combined with Box-Behnken response surface methodology experiment can effectively optimize the extraction process of total alkaloids from Sophora moorcroftiana seeds by supercritical fluid CO₂ extraction technology,and obtain the optimal extraction conditions.UPLC-MS can well validate the total alkaloids from Sophora moorcroftiana seeds,and can be used to investigate the pharmacokinetics of total alkaloids from Sophora moorcroftiana seeds in normal SD rats.