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Pharmaceutical Biology Volume 54, 2016 - Issue 9
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Research Article

Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS

Shuping LiThe MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; ;Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China;
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Liang TengThe MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; ;Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China;
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Wei LiuThe MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China;
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Xuemei ChengThe MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; ;Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai, China
,
Bo JiangThe MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China;
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Zhengtao WangThe MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; ;Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai, China
&
Chang-hong WangThe MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; ;Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai, ChinaCorrespondence[email protected]
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Pages 1768-1781 | Received 19 Apr 2015, Accepted 28 Nov 2015, Published online: 05 Jan 2016

Figures & data

Figure 1. Chemical structures and product ion spectra of harmane (a); harmine (b); IS (c); M1–M3 (d); M4 (e); M5 (f); M6, M7 and M9 (g); M19 and M20 (h).

Figure 1. Chemical structures and product ion spectra of harmane (a); harmine (b); IS (c); M1–M3 (d); M4 (e); M5 (f); M6, M7 and M9 (g); M19 and M20 (h).

Table 1. The optimized MS analytical parameters of harmane, its 10 metabolites, harmine and IS.

Figure 2. Representative MRM chromatograms of blank rat plasma sample (a); blank plasma spiked with harmane and harmine at LLOQ and IS (b); and plasma sample spiked with IS after oral administration of harmane at a dose of 30.0 mg/kg (c).

Figure 2. Representative MRM chromatograms of blank rat plasma sample (a); blank plasma spiked with harmane and harmine at LLOQ and IS (b); and plasma sample spiked with IS after oral administration of harmane at a dose of 30.0 mg/kg (c).

Table 2. Accuracy, precision, extraction recovery, matrix effect, and stability of harmane, harmine and IS in rat plasma (n = 5).

Figure 3. Mean plasma concentration–time curves of harmane in rats after intravenous and oral administration at doses of 1.0 and 30.0 mg/kg, respectively.

Figure 3. Mean plasma concentration–time curves of harmane in rats after intravenous and oral administration at doses of 1.0 and 30.0 mg/kg, respectively.

Figure 4. Mean plasma concentration–time curves of phase I metabolites after intravenous administration of harmane at a dose of 1.0 mg/kg (a); phase I metabolites after oral administration of harmane at a dose of 30.0 mg/kg (b); phase II metabolites after intravenous administration of harmane at a dose of 1.0 mg/kg (c); and phase II metabolites after oral administration of harmane at a dose of 30.0 mg/kg (d).

Figure 4. Mean plasma concentration–time curves of phase I metabolites after intravenous administration of harmane at a dose of 1.0 mg/kg (a); phase I metabolites after oral administration of harmane at a dose of 30.0 mg/kg (b); phase II metabolites after intravenous administration of harmane at a dose of 1.0 mg/kg (c); and phase II metabolites after oral administration of harmane at a dose of 30.0 mg/kg (d).

Table 3. Pharmacokinetic parameters of harmane and its 10 metabolites (M1–M7, M9, M19 and M20) in rats after intravenous administration of harmane at a dose of 1.0 mg/kg (mean ± SD, n = 8).

Table 4. Pharmacokinetic parameters of harmane and its 10 metabolites (M1–M7, M9, M19 and M20) in rats after oral administration of harmane at a dose of 30.0 mg/kg (mean ± SD, n = 8).

Figure 5. Comparison of the absolute bioavailability of harmane and its 10 metabolites (M1–M7, M9, M19 and M20) in rats after oral administration of harmane at a dose of 30.0 mg/kg.

Figure 5. Comparison of the absolute bioavailability of harmane and its 10 metabolites (M1–M7, M9, M19 and M20) in rats after oral administration of harmane at a dose of 30.0 mg/kg.

Figure 6. Mean plasma concentration–time curves of harmane (a) and harmine (b) in normal and test rats after intravenous and oral administration of harmane.

Figure 6. Mean plasma concentration–time curves of harmane (a) and harmine (b) in normal and test rats after intravenous and oral administration of harmane.

Figure 7. Proposed metabolic pathways of harmane: the present proposed metabolic pathways of harmane in rats after intravenous and oral administration of harmane at doses of 1.0 and 30.0 mg/kg, respectively (a); the published proposed metabolic pathways for harmane and harmine (b) (Guan et al. Citation2001).

Figure 7. Proposed metabolic pathways of harmane: the present proposed metabolic pathways of harmane in rats after intravenous and oral administration of harmane at doses of 1.0 and 30.0 mg/kg, respectively (a); the published proposed metabolic pathways for harmane and harmine (b) (Guan et al. Citation2001).

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