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Molecules 2018, 23(1), 227; https://doi.org/10.3390/molecules23010227

A Comparative Pharmacokinetic Study by UHPLC-MS/MS of Main Active Compounds after Oral Administration of Zushima-Gancao Extract in Normal and Adjuvant-Induced Arthritis Rats

1
Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China
2
State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
3
Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Nanjing 210023, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 18 December 2017 / Revised: 11 January 2018 / Accepted: 18 January 2018 / Published: 22 January 2018
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Abstract

A sensitive and rapid ultra high-performance liquid-chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been applied to investigate the influence of rheumatoid arthritis (RA) on the pharmacokinetics of nine analytes (daphnetin, daphnoretin, 7-hydroxycoumarin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid), which are major active components in Zushima-Gancao extract. The analytes and internal standard (IS) were separated in a Hypersil Gold C18 column and detected on a triple-stage quadrupole mass spectrometer using the validated method. All analytes exhibited good linearities (R2 > 0.98), and the lower limit of quantification (LLOQs) were sufficient for quantitative analysis. Intra- and inter-batch precision were all within 14.96% while the accuracy of nine analytes ranged from −17.99 to 14.48%, and these results were all within acceptance criteria. The extraction recoveries, matrix effects, and stabilities were all satisfactory. Main pharmacokinetic parameters of each compound were compared, and significant differences were found in parameters of daphnetin, daphnoretin, liquiritin, isoliquiritin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid, especially the last one, between the two groups. Therefore, adjuvant-induced arthritis has different effects on the pharmacokinetics of ingredients in Zushima-Gancao extract. The comparative pharmacokinetic study between normal and adjuvant-induced arthritis rats might provide more comprehensive information to guide the clinical usage of Zushima-Gancao extract for treating RA. View Full-Text
Keywords: Zushima-Gancao extract; UHPLC-MS/MS; rheumatoid arthritis; pharmacokinetics Zushima-Gancao extract; UHPLC-MS/MS; rheumatoid arthritis; pharmacokinetics
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Shan, J.; Qian, W.; Peng, L.; Chen, L.; Kang, A.; Xie, T.; Di, L. A Comparative Pharmacokinetic Study by UHPLC-MS/MS of Main Active Compounds after Oral Administration of Zushima-Gancao Extract in Normal and Adjuvant-Induced Arthritis Rats. Molecules 2018, 23, 227.

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