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In order to investigate the pharmacokinetics of tropane alkaloids in Hyoscyamus niger L., a sensitive and specific high-performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of atropine, scopolamine, and anisodamine in rat plasma is developed and fully validated, using homatropine as an internal standard. The separation of the four compounds was carried out on a BDS Hypersil C18 column using a mobile phase consisting of acetonitrile and water (containing 10 mmol ammonium acetate). Calibration curves were linear from 0.2 to 40 ng/mL for atropine, scopolamine, and from 0.08 to 20 ng/mL for anisodamine. The precision of three analytes was <5.89% and the accuracy was between -1.04 to 2.94%. This method is successfully applied to rat pharmacokinetics analysis of the three tropane alkaloids after oral administration of H. niger extract. The maximum concentration of these three tropane alkaloids was reached within 15 min, and the maximum concentrations were 31.36 ± 7.35 ng/mL for atropine, 49.94 ± 2.67 ng/mL for scopolamine, and 2.83 ± 1.49 ng/mL for anisodamine. The pharmacokinetic parameters revealed areas under the curve of 22.76 ± 5.80, 16.80 ± 3.08, and 4.31 ± 1.21 ng/h mL and mean residence times of 2.08 ± 0.55, 1.19 ± 0.45, and 3.28 ± 0.78 h for atropine, scopolamine, and anisodamine, respectively.

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Background Coptidis Rhizome (CR), widely applied to treat with heat and toxicity, is one of the most commonly used traditional Chinese medicine (TCM), however, an extensive dosage can induce toxicity. Diarrhea is one of the most frequent side effects of CR treatment.Methodology/Principal FindingsIn this study, metabonomics was combined with the multivariate statistical analysis to discover the endogenous metabolites which related to the diarrheal induced by CR. The male Sprague–Dawley rats were dosed with 4.95 g CR/kg weight. Urine samples were collected at day −1 (before treatment), and days 14 and 21 for NMR analysis. Serum and tissues were collected at day 14 for GC-MS analysis and histopathological examination, respectively. The urine and serum metabolic profiles provided clearer distinction between CR-treated group and control group, which was confirmed by body weight change and diarrhea. Through multivariate statistical analysis, 12 marker metabolites from 1H NMR and 8 ones from GC-MS have been found. Among those metabolites, hippurate, acetate, alanine, glycine and glutamate are likely to break the balance of gut microbiota, whereas, lactate and 2-ketoisovalerate showed association with energy metabolism. Meanwhile, we observed that the CR-induced toxicity will recover when the treatment was stopped.Conclusions/significanceThese results suggest that the main reason for the CR-associated diarrhea might be disturbance in the normal gut microbiota. This metabonomics approach may provide an effective way to study the alteration of gut microbiota, which is expected to find broader application in other drug-induced gastrointestinal reaction assessment.