Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats
To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetini...
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| Published in | Molecules (Basel, Switzerland) Vol. 27; no. 14; p. 4657 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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| Abstract | To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent Cmax (2377.57 ng/mL), Tmax (5 min) and AUC0-T (6625.54 mg/L*h), which was much higher than the Cmax (346.03 ng/mL), Tmax (2.00 h) and AUC0-T (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG. |
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| AbstractList | To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent Cmax (2377.57 ng/mL), Tmax (5 min) and AUC0-T (6625.54 mg/L*h), which was much higher than the Cmax (346.03 ng/mL), Tmax (2.00 h) and AUC0-T (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG. To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent Cmax (2377.57 ng/mL), Tmax (5 min) and AUC0-T (6625.54 mg/L*h), which was much higher than the Cmax (346.03 ng/mL), Tmax (2.00 h) and AUC0-T (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG.To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent Cmax (2377.57 ng/mL), Tmax (5 min) and AUC0-T (6625.54 mg/L*h), which was much higher than the Cmax (346.03 ng/mL), Tmax (2.00 h) and AUC0-T (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG. To understand that 18β-Glycyrrhetic acid 3-O-mono- β -D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent C max (2377.57 ng/mL), T max (5 min) and AUC 0-T (6625.54 mg/L*h), which was much higher than the C max (346.03 ng/mL), T max (2.00 h) and AUC 0-T (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG. |
| Author | Yang, Jian-Guo Cao, Mengxin Wu, Chenyao Yang, Yongan Zuo, Jiawei Zhu, Lili Tang, Wenjian |
| AuthorAffiliation | 2 Huainan Municipal Food and Drug Inspection Center, Huainan 232000, China 3 Jiangsu Nature Biological Engineering Technology Co., Ltd., Nanjing 210023, China; yangyan73@163.com 1 Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Anhui Medical University, Hefei 230032, China; caomengxin0711@163.com (M.C.); zuojiawei2022@163.com (J.Z.); yangjgyx@163.com (J.-G.Y.); chengyao.wu@hotmail.com (C.W.) |
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| Author_xml | – sequence: 1 givenname: Mengxin surname: Cao fullname: Cao, Mengxin – sequence: 2 givenname: Jiawei surname: Zuo fullname: Zuo, Jiawei – sequence: 3 givenname: Jian-Guo surname: Yang fullname: Yang, Jian-Guo – sequence: 4 givenname: Chenyao surname: Wu fullname: Wu, Chenyao – sequence: 5 givenname: Yongan surname: Yang fullname: Yang, Yongan – sequence: 6 givenname: Wenjian orcidid: 0000-0002-2798-6557 surname: Tang fullname: Tang, Wenjian – sequence: 7 givenname: Lili surname: Zhu fullname: Zhu, Lili |
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