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Purpose: To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of single- and multiple-dose SPH3127 in healthy individuals., Methods: This was a randomized, double-blind, placebo-controlled, Phase I dose-escalation study., Findings: SPH3127 exposure, expressed as C max , AUC 0-t , and AUC 0-∞ , was proportionally increased with dose for a range of 25-800 mg (single ascending dose [SAD]) and 100-400 mg daily (multiple ascending doses [MADs]). In an SAD, the C max values with 25, 50, 100, 200, 400, and 800 mg of SPH3127 were 90.67, 344.50, 523.50, 1239.50, 2445.00, and 5753.33 ng/mL, respectively. The corresponding AUC 0-t values were 294.48, 843.62, 1109.33, 2858.56, 6697.50, and 13057.83 h × ng/mL. In MADs, after the first dose of SPH3127, the C max values with 100, 200, and 400 mg of SPH3127 were 421.50, 969.00, and 2468.33 ng/mL, respectively. The corresponding AUC 0-t values were 1279.28, 2275.77, and 5934.26 h × ng/mL. At steady state, the C max values with 100, 200, and 400 mg of SPH3127 were 514.67, 1419.17, and 2513.33 ng/mL, respectively. The corresponding AUC 0-24 values were 1638.14, 3096.20, and 7577.70 h × ng/mL. The median T max range from 0.33 to 1.0 h and the median t 1/2 from 3 to 4 h. In an SAD, when the dose was >100 mg, plasma renin activity inhibition of up to 90% lasted up to 24 h. In MADs, renin activity was continuously inhibited by up to 90% in each group for 24 h after the last administration. Treatment-emergent adverse events (AEs) were reported in 29.2% of individuals receiving the SAD and 33.3% of those receiving MADs. Only mild adverse events occurred., Implications: SPH3127 was well tolerated and had robust and sustained suppression of plasma renin activity. CLINICALTRIALS., Gov Identifiers: NCT03128138 (SAD study) and NCT03255993 (MAD study)., Competing Interests: DISCLOSURES The authors have indicated that they have no conflicts of interest regarding the content of this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A rapid and high-sensitivity liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for simultaneous determination of nine active constituents (baicalin, baicalein, wogonoside, wogonin, scutellarin, berberine, coptisine, ginsenoside Rb1 and ginsenoside Re) in rat plasma after oral administration of Banxia xiexin decoction (BXD). Biological samples were processed wtih acetone-ethyl acetate (4:1, v/v). The mobile phase consisted of methanol and water (containing 0.1% formic acid) with gradient elution at a flow rate of 0.3 mL/min. Detection was performed on a triple quadrupole mass spectrometer using positive ion and negative ESI in the multiple reaction monitoring mode. The calibration curves for all analytes had good linearity (r > 0.9933). The mean recovery of all the nine active ingredients was >75.2%, and the intra- and inter-day precisions were within 12.0%; the accuracy was between 87.4 and 110.4%. This method was successfully applied to a pharmacokinetic study after administration of BXD. The results of the pharmacokinetic study might be helpful for BXD reasonable clinical application and further studies on mechanism., (Copyright © 2017 John Wiley & Sons, Ltd.)

Banxia Xiexin decoction (BXD) is an effective Chinese Medicinal Prescription in treating gastroenteritis diseases. In this study an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to separate and determine 18 major active ingredients of BXD in order to guarantee quality. The separation of ten flavonoids, four alkaloids and four saponins was accomplished on an Acquity BEH C18 (2.1mm×100mm, 1.7μm) column using gradient elution with 0.1% (v/v) formic acid water (A) and 0.1% (v/v) formic acid in methanol (B). All the analytes were detected in positive electrospray ionization tandem mass spectrometry by selective reaction monitoring (SRM) mode. A good linear regression relationship for each analyte was obtained over the range from 2.41-438ng/ml to 20.75-4150ng/ml. The precision was evaluated by intra- and inter-day assays with relative standard deviation (RSD) less than 7.7%. The recovery measured at three concentration levels varied from 92.4% to 107.8%. The method sensitivity expressed as LOQ was typically 0.97-4.15ng/ml. The assay was successfully applied for determination of the 18 bioactive compounds in BXD. The results indicated that the new UPLC-MS/MS method was rapid and accurate, and could be reliably utilized as a quality control method for BXD., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: Using rat everted gut sacs to investigate the intestinal absorption characteristics of flavones in Gegenqinlian decoction and different compatibilities., Method: In the research, the intestinal absorption mechanism of the active ingredients including puerarin, daidzin, liquiritin, scutellarin, baicalin and wogonoside in Gegenqinlian decoction were studied; and then the influences of different intestinal segments, different drug concentrations on the absorption of ingredients were discussed; finally, the absorption characteristics of the active compounds in different compatibility were also be compared., Result: The absorption mode of the six compounds we disscussed was linearity, R2 > 0.9, which was consistent with the zero order rate process. The mechanism of absorption of puerarin, daidzin, liquiritin and scutellarin across intestinal sacs was passive diffusion, while active transportation was also existed. The Ka of baicalin and wogonoside increased along with the raising dosage, which indicated the passive absorption of the two ingredients. Different parts of the intestinal absorption experiments of Gegenqinlian decoction showed that the best absorption site of puerarin, daidzin and scutellarin was jejunum; liquiritin and baicalin can be absorbed better in colon; and the best absorption part of wogonoside was ileum. In the section of comparing the Ka of different compatibilities, it was founded that the absorption of puerarin, daidzin, liquiritin, baicalin in Gegenqinlian decoction were best; in the four intestinal segments, scutellarin and wogonoside were also absorbed best in Gegenqinlian decoction except for the duodenum where the best compatibility was Gegenqinlian group., Conclusion: For ingerdients, there was selective absorption in intestinal sacs. The intestinal absorption characteristics of each component in different compatibilities were different, however, the Gegenqinlian decoction was the optimal.