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Pharmacokinetic Studies of Three Alkaloids in Rats After Intragastrical Administration of Lycopodii Herba Extract by LC-MS/MS

Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
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Molecules 2019, 24(10), 1930; https://doi.org/10.3390/molecules24101930
Received: 2 May 2019 / Revised: 16 May 2019 / Accepted: 17 May 2019 / Published: 19 May 2019
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Abstract

Lycopodii Herba is a widely used traditional medicinal herb, and contains diverse fascinating alkaloids. In this study, a fast and sensitive LC-MS/MS method for the simultaneous determination of lycodoline, α-obscurine, and N-demethyl-α-obscurine from Lycopodii Herba in rat plasma and brain tissue was developed and validated. Biological samples were extracted via a protein precipitation procedure using methanol as the extraction solvent and Huperzine B as the internal standard. Chromatographic separation was carried out using a Thermo Syncronis-C18 column (50 mm × 2.1 mm, 5 μm) and a gradient mobile phase containing methanol and water with 0.05% formic acid. The three alkaloids were detected by positive electrospray ionization in selective reaction monitoring mode. The selectivity, crosstalk, carryover effect, linearity, accuracy, precision, extraction recovery, matrix effect, and stability of the current method were validated. Then, using the validated method, the plasma pharmacokinetics and brain tissue distribution of the alkaloids in rats were investigated after intragastrical administration of Lycopodii Herba extract. The three alkaloids were shown to be rapidly absorbed into the blood (Tmax, 0.79–1.58 h), and then also eliminated rapidly (t1/2, 1.27–2.24 h). All of them could pass through the blood–brain barrier. The method provides a new research approach to expand preclinical studies of Lycopodii Herba. View Full-Text
Keywords: Lycopodii Herba; lycodoline; α-obscurine; N-demethyl-α-obscurine; pharmacokinetics; brain tissue distribution; liquid chromatography–tandem mass spectrometry Lycopodii Herba; lycodoline; α-obscurine; N-demethyl-α-obscurine; pharmacokinetics; brain tissue distribution; liquid chromatography–tandem mass spectrometry
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Ma, D.; Gu, X.; Wang, X.; Liu, Y.; Di, X. Pharmacokinetic Studies of Three Alkaloids in Rats After Intragastrical Administration of Lycopodii Herba Extract by LC-MS/MS. Molecules 2019, 24, 1930.

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