Simultaneous quantification of evodiamine, rutaecarpine, and dehydroevodiamine in rat cerebrospinal fluid and cerebral nuclei after oral administration by UPLC-MS/MS

doi:10.5246/jcps.2022.01.002

Abstract

Abstract:

Evodiamine, rutaecarpine, and dehydroevodiamine have been demonstrated as the major alkaloids in the fruits of Euodia rutaecarpa, a well-known traditional Chinese medicine with central nervous system activities. To study their cerebrospinal fluid pharmacokinetics and cerebral nuclei distribution, the alkaloids were mixed at the weight ratio of 1:1:1 and orally administered via gavage to the rats at each dose of 15 mg/kg. A quick and reliable ultra-performance liquid chromatographic-tandem mass spectrometry method was developed and applied for the simultaneous analysis of the alkaloids in rat cerebrospinal fluid and cerebral nuclei collected at different time points. Non-compartmental pharmacokinetic profiles were calculated, and the distribution in cerebral nuclei was compared. All the tested compounds were absorbed into rat cerebrospinal fluid and distributed to the brain nuclei quickly. Their distribution in different nuclei varied, as evodiamine mainly in cerebellum and brainstem, rutaecarpine with its maximum in the brainstem, and dehydroevodiamine mostly in the cerebellum and hippocampus. They were eliminated from the brain rapidly without long-time accumulation. In summary, this study revealed the targeting discrepancy of evodiamine, rutaecarpine, and dehydroevodiamine in the brain, and highlighted the possibility for drug candidates in the encephalopathy treatment of the fruits of E. rutaecarpa.

Key words: Evodiamine, Rutaecarpine, Dehydroevodiamine, Cerebrospinal fluid, Cerebral nuclei, UPLC-MS/MS

Supporting:

Yanfang Yang, Yinan Zhang, Youbo Zhang, Xiuwei Yang. Simultaneous quantification of evodiamine, rutaecarpine, and dehydroevodiamine in rat cerebrospinal fluid and cerebral nuclei after oral administration by UPLC-MS/MS[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(1): 13-22.

Figures/Tables 8

Table 1. Optimized MRM parameters of evodiamine, rutaecarpine, and dehydroevodiamine in mass detection.

Table 2. The regression data, LLOQs, and LLODs of evodiamine, rutaecarpine, and dehydroevodiamine in cerebrospinal fluid and brain homogenate.

Table 3. The precision, accuracy, recovery, matrix effect, and stability of evodiamine, rutaecarpine, and dehydroevodiamine in cerebrospinal fluid and brain homogenate.

Table 4. Pharmacokinetic parameters of evodiamine, rutaecarpine, and dehydroevodiamine in rat cerebrospinal fluid after oral administration of their mixture at each dose of 15 mg/kg (mean ± SD, n = 6).

Table 5. AUC0→∞ of evodiamine, rutaecarpine, and dehydroevodiamine in rat cerebral nuclei after oral administration of their mixture at each dose of 15 mg/kg (ng?min/mL, mean ± SD, n = 6).

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