peoniflorin and nuciferine

Diabetes is a chronic disease associated with significant morbidity and mortality. Tangzhiqing tablet (TZQ), a Chinese traditional patent medicine, has been in phase 2 clinical trial for the treatment of diabetes mellitus. However, the current quality evaluation of TZQ still remains rather obscure.. The promising quality markers (Q-markers) of TZQ will be sought for its quality assessment and process control based on the qualitative, quantitative and dose-exposure-response analysis.. The fingerprint analysis of TZQ was carried out through ultra high performance liquid chromatography- quadrupole time-of-flight/ mass spectrometry (UPLC-Q-TOF/MS) assay. Multicomponent quantitative analysis was implemented to the main ingredients of nuciferine, paeoniflorin, salvianolic acid B, hyperoside and rutin in TZQ by means of LC analysis. The dose-exposure-response relationship of TZQ was revealed by a placebo-controlled, 5-way crossover study in healthy Chinese subjects. The potential Q-markers in plasma were determined by a liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) method. The therapeutic effect of TZQ was expressed as the glucose-lowering profile. The exposure-response relevance was developed between the concentration of Q-markers and the glucose-lowering effect of TZQ.. 46 compounds were identified or tentatively characterized from TZQ. The contents of paeoniflorin, nuciferine, salvianolic acid B, hyperoside and rutin in TZQ were 6.40, 1.75, 1.70, 0.004, and 0.006 mg, respectively. However, salvianolic acid B, hyperoside and rutin could hardly be detected in human plasma under the current LC-MS/MS condition. The exposures of nuciferine and paeoniflorin (AUC. Nuciferine and paeoniflorin were identified as the promising Q-markers of TZQ based on the fingerprint qualitative analysis, multicomponent quantitative analysis and dose-exposure-response analysis. The two Q-markers are meaningful to ensure the quality assessment and process control of TZQ.

Topics: Adult; Aporphines; Biomarkers; Blood Glucose; Chromatography, High Pressure Liquid; Cross-Over Studies; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Glucosides; Humans; Male; Medicine, Chinese Traditional; Monoterpenes; Tablets; Tandem Mass Spectrometry

A quality marker (Q-marker) is defined as an inherent chemical compound that is used for the quality control of a drug. Its biological activities are closely related to safety and therapeutic effects. Generally, a multiple-component herbal medicine may have many Q-markers. We therefore proposed a concept of "super Q-marker" satisfying both the criterion of Q-markers and PK-markers to be used in more effective quality control of herbal medicine.. The first aim was to find suitable prototype-based PK-markers from Tangzhiqing tablets (TZQ), a Chinese patent medicine. Then super Q-markers were expected to be identified from the prototype-based PK-markers based on an in vitro-in vivo correlation study.. Potentially eligible prototype-based PK-markers were identified in a single- and multiple-dose pharmacokinetic study on TZQ in 30 healthy volunteers. The in vitro dissolution and permeation profiles of the prototype-based PK-markers of TZQ were evaluated by the physiologically-based drug dissolution/absorption simulating system (DDASS). An in vitro-in vivo correlation analysis was conducted between the dissolution/permeation behaviors in DDASS and the actual absorption profiles in human to test the transferability and traceability of the promising super Q-markers for TZQ.. In human, plasma paeoniflorin and nuciferine as prototype-based PK-markers exhibited the appropriate pharmacokinetic properties, including dose-dependent systemic exposure (AUC, C. Paeoniflorin and nuciferine are identified as the super Q-markers from the prototype-based PK-markers of TZQ based on findings from a combination of in vitro, in vivo, and in vitro-in vivo correlation studies. This method is practical for optimal identification of qualified Q-markers, thus helping improve the quality control of herbal medicines.

Topics: Administration, Oral; Adult; Aporphines; Biomarkers, Pharmacological; Drug Liberation; Drugs, Chinese Herbal; Female; Glucosides; Humans; Male; Monoterpenes; Quality Control; Tablets

As one of the new drugs of traditional Chinese medicine, Sanye Tablet is employed as a hypolipidemic in the traditional medicine, but the biopharmaceutical properties of the drug is still unclear.. Through the study of biopharmaceutical properties, the classical biopharmaceutics classification system (BCS) can be used to classify and predict the in vivo absorption properties. On this basis, the biopharmaceutical properties closely related to traditional Chinese medicine preparations are added and a modified BCS model is established to predict and judge the absorption degree of traditional Chinese medicine compound.. Representative components of Sanye Tablet were selected and subjected to different in vitro tests. The experimental results were compared with the results of the BCS to evaluate the accuracy and applicability to Sanye Tablet. We take parameters of dissolution and stability based on product characteristics into account. A "modified-BCS" was developed and the results of the improved method and the classic method were compared. Also the ability of each classification system to predict and determine the extent of absorption of the Chinese herbal compound was investigated based on the absolute bioavailability of representative components.. For classic BCS, the five representative components (except for nuciferine) are all class III, nuciferine is class I/II obtained by Caco-2 cell assay and class III/IV obtained by everted gut sac assay. For modified BCS, paeoniflorin is class III, rutin, hyperoside and salvianolic acid B are class III/IV, and nuciferine is class I/II based on Caco-2 cell assay, class III/IV based on everted gut sac assay. Nuciferine is the best of the five components, with absolute bioavailability reaching 61.91% based on in vivo bioavailability test.. The five representative components (except for nuciferine) are all class III/IV, which correlates well with the absolute bioavailability results and demonstrates that they are poorly absorbed substances. The correlation between the classification results obtained using the "modified-BCS" and absorption in the body is better than the correlation obtained using the classic method, suggesting that the improved BCS is more suitable for the characterization of Sanye Tablet. These results indicate that the oral formulation of Sanye Tablet is a BCS III/IV drug.

Topics: Animals; Aporphines; Biopharmaceutics; Caco-2 Cells; Drugs, Chinese Herbal; Glucosides; Humans; Hypoglycemic Agents; Intestinal Absorption; Male; Medicine, Chinese Traditional; Models, Biological; Monoterpenes; Quercetin; Rats, Sprague-Dawley; Rutin