Optimization of supercritical-CO2 extraction and pharmacokinetics in SD rats of alkaloids form Sophora moorcroftiana seed

Abstract

The total alkaloids extracted from the seeds of Sophora moorcroftiana (TAs-SM) have the potential to treat alveolar echinococcosis, a disease included by the WHO in a list of 17 key neglected diseases world-wide. The aims of the current study were first to develop a supercritical fluid extraction (SFE) method for optimizing TAs-SM extraction, and second, to develop an optimized method for evaluating TAs-SM pharmacokinetics in vivo. The Box–Behnken response surface method was used to optimize the extraction process, and ultra-high liquid chromatography coupled with high resolution electrospray mass spectrometry (UPLC-HR-ESI-MS) was used to determine the pharmacokinetics of TAs-SM in SD rats. The results indicated the following optimal SFE extraction conditions: pressure = 31 MPa, temperature = 70 °C, time = 162.18 min. With these parameters, total alkaloids could be extracted from each gram of S. moorcroftiana, with the total content being 68.88 μg. The linear range of UPLC-HR-ESI-MS is 0.78–200.00 ng/ml, R2 > 0.99, and the sample recovery is 99–113%. The precision, accuracy, selectivity and stability of the method meet the requirements of US FDA guidelines. To our knowledge this study is the first to establish an SFE method for extracting TAs-SM and the first to employ UPLC-HR-ESI-MS for measuring TAs-SM in rats. These findings provide important contributions for using TAs-SM in further drug development and clinical applications.