ABSTRACT
To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates, an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSn) method and BitterX database prediction. The chromatographic operating conditions were as follows, chromatographic column: Acquity UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm), mobile phase: 0.1% formic acid-water solution (A)-acetonitrile (B) with gradient elution. The data were collected in positive and negative ion modes, respectively. The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry. The compounds were identified by combining retention time, reference substances, reports, and other relevant data, and a total of 57 constituents including flavonoids, alkaloids, and phenylpropanoids were finally identified. Further, the BitterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes, finally 33 potential bitter compounds, including kukoamine A and linarin, were predicted. This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates, it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.
ABSTRACT
OBJECTIVE: To analyze the effects of "adjusting structure and vacating space" of the transparent medicines procurement basing health insurance reimbursement standards, through comparing medicines consumption structure of health insurance designated health facilities of Fujian province. And to generate evidence as well as to propose recommendations for policy improvement and experience promotion. METHODS: Based on the 2016 and 2017 provincial medicines pooled procurement database, adopting the pivot table statistical functions of EXCEL software, the consumption value and value in proportion of Class and Ⅱ chemical products (Fujian provincial medicines procurement list therapeutic classification for chemical products), as well as active pharmaceutical ingredients, consumption value and volume (standardized units in tablet/bottle/vial) of originator and generics were analyzed and compared. The consumption value of Class formulations of traditional Chinese medicines (Fujian provincial medicines procurement list therapeutic classification for formulations of traditional Chinese medicines) was also analyzed and compared. RESULTS: Nearly 2.38 billion yuan procurement budget was saved in 2017 through adjustment of the medicines procurement list in Fujian province. There were a certain changes of the consumption structure of medicines. The procurement value of adjuvant and nutraceutical medicines dramatically reduced. The procurement value of medicines for treatment of chronic diseases like hypertension and cancers significantly increased. The procurement volume of generics started to surpass that of the originator, and showed potential competitiveness of generic substitution. However, the originator still dominated the market of quite a number of medicines. Prices of both generics and originators decreased. CONCLUSION: The effect of “adjusting structure and vacating space” has been demonstrated. Fully implementation of the health insurance reimbursement standards will make the above effect more apparent. To promote effective generic competition, Fujian should set the same health insurance reimbursement standard for originator and its generics (quality and efficacy validated) to promote generics substitution.