Comparative pharmacokinetics and metabolites study of seven major bioactive components of Shaoyao‐Gancao decoction in normal and polycystic ovary syndrome rats by ultra high pressure liquid chromatography with tandem mass spectrometry

Abstract

A simple and sensitive liquid chromatography with tandem mass spectrometry method was developed for simultaneous quantification of paeoniflorin, albiflorin, oxypaeoniflorin, liquiritin, liquiritigenin, glycyrrhetinic acid, and glycyrrhizin in rat plasma after oral administration of Shaoyao-Gancao decoction, which is traditionally used in the treatment of polycystic ovary syndrome. The plasma samples were pretreated with methanol as precipitant. The method exhibited good linearity (correlation coefficient (R 2 ) > 0.99) with lower quantification limits of 0.595-4.69 ng/mL for all analytes. Intra-and interbatch precision, accuracy, recovery, and stability of the method were all within accepted criteria. The results showed that the pharmacokinetic behaviors of the seven compounds were altered in the pathological status of polycystic ovary syndrome. Furthermore, a total of 36 metabolites were structurally identified based on their accurate masses and fragment ions. The major metabolic pathway involves phase I metabolic reactions (such as hydroxylation), phase II metabolic reactions (such as sulfation and glucuronidation conjugation) as well as the combined multiple-step metabolism. This study is the first report on the pharmacokinetic and metabolic information of Shaoyao-Gancao decoction in both normal and model rats, which would provide scientific evidences for the bioactive chemical basis of herbal medicines and also promote the clinical application of Shaoyao-Gancao decoction for treating polycystic ovary syndrome. K E Y W O R D Sacokinetics, pharmacokinetics, polycystic ovary syndrome, tandem mass spectrometry, traditional Chinese medicine Article Related Abbreviations: AUC 0-∞ , total area under the plasma concentration-time curve from time zero to time infinity; AUC 0-t , total area under the plasma concentration-time curve from time zero to time t; C max , peak plasma concentration; CE, collision energy; DMPK, drug metabolism and pharmacokinetics; GU, Glycyrrhizae uralensis; IS, internal standard; LLOQ, linearity and low limits of quantification; MRM, multiple reaction monitoring; PCOS, polycystic ovary syndrome; QC, quality control; QTRAP, triple quadrupole-linear ion trap; RP, Radix Paeoniae Alba; SGD, Shaoyao-Gancao decoction; T 1/2 , elimination half-life; TCM, traditional Chinese medicine; T max , time to reach C max .Jun-jin Liu and Yao Cheng contribute equally to this paper. 2534

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

“…After 1°week of acclimatization, the PCOS rats model was induced as described previously ( Liu et al, 2019 ). In brief, animals were orally administrated daily with 1 mg/kg letrozole for 21 consecutive days.…”

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