Exploring the scientific rationality of “Different dosage forms of the same prescription” base on Q-markers of pulvis and pill of Chuanxiong Chatiao Prescription

Abstract

Objective: To predict and analyze the potential Q-markers of Chuanxiong Chatiao Prescription, and the pharmacokinetic properties of pulvis and pills in vivo were studied, which provided a basis for the rational evaluation of the phenomenon of “Different Dosage Forms of the Same Prescription”. Methods and Material: Q-markers analysis of Chuanxiong Chatiao Prescription based on the “Five Principles” (traceability and transmissibility, specificity, effectiveness, prescription compatibility and testability). The content determination method of Q-markers in Chuanxiong Chatiao Prescription was established by UPLC, and the content difference of Q-markers in the two dosage forms ware determined and compared. The Q-markers in rabbit plasma was determined by LC-MS / MS method, and the pharmacokinetic parameters of Q-markers in pulvis and pills were analyzed. Results: A total of 16 potential Q-markers from the “Five Principles” were used, nine components of tetramethylprazine, ferulic acid, glycyrrhizin, glycyrrhizic acid, luteolin, cimicifugoside, senkyunolide Ⅰ, isoimperatorin, nodakenin were identified as Q-markers of Chuanxiong Chatiao Presciption. The content of tetramethylprazine and other components in the pulvis form was found to be significantly higher than that in the pills, while the content of senkyunolide Ⅰ was lower than that in the pills, which may be related to the preparation process of the dosage form and the physicochemical properties of the components. Compared with pulvis, the Tmax and t 1/2 of ferulic acid and other components in pills were significantly prolonged. To a certain extent, it can explain the classical theory of traditional Chinese medicine “Components in pulvis release quickly and take effect in fast-acting manner, while in pills release slowly and take effect in slow-acting”. Meanwhile, the Cmax and AUC0-t of tetramethylprazine and other components in pills were higher than those in pulvis, which showed unexpected pharmacokinetic characteristics, indicating the complexity of compounding and the importance of dosage form design. Conclusions: A method for the determination of Q-markers content was established by UPLC, which provide reference for the quality control of Chuanxiong Chatiao Prescription. In vivo studies have found the pharmacokinetic parameters indicate the absorption and distribution characteristics of pulvis and pills. However, it is also found that the release behavior of different components not only affected by the dosage form but also closely related to their own physical and chemical properties