| Angiotensin Ⅱ receptor blockers(ARBs),are first-line medicaments for hypertension.However,their use also poses risks.For decades,since Losartan was marketed in 1994,better and safer ARBs,which are obtained by structural modification and transformation of sartan drugs,were explored and developed continuously.In 2015,Zhi-Ming Zhou’s group designed and synthesized a class of novel angiotensin Ⅱ receptor blockers bearing 6-subs tituted carbamoyl benzimidazoles with a chiral center.The preliminary experimental results revealed that the bioactivities of certain compounds were superior to that of Losartan,and the antagonists with R configurations always had a higher bindingaffinity than those with S configurations.This work was supported by the National Technological Project of the Manufacture and Innovation of Key New Drugs.However,they encountered problem that the chiral analogues was difficult to separation during the research.In this background,enantioseparation of chiral 6-substituted carbamoyl benzimidazoles was presented in this paper,and the chiral recognition mechanism was discussed to direct enantioseparation of their structural analogue.In this study,enantioseparation of thirteen chiral 6-substituted carbamoyl benzimidazoles on two immobilized polysaccharide-based chiral stationary phases Chiralpak IA and Chiralpak IC was evaluated for the first time.Most of the examined compounds obtained baseline separation directly on CSPs.The effects of a polar alcohol modifier,analyte structure,and column temperature on the chiral recognition were investigated.Furthermore,the chiral recognition mechanism was discussed preliminarily based on the thermodynamic parameters.Interestingly,two unusual phenomena were observed:(1)an unusual increase in retention with increasing temperature and(2)an extremely high Tiso value(i.e.,several thousand degrees centigrade).We gave the preliminary explaination about the above two phenomenon in the view of thermodynamics and the analytes’ structural features,respectively.Furthermore,by using R-(+)-α-methylbenzylamine as pre-column derivatization reagent,the compound 7 which can not be directly separation on Chiralpak IA or Chiralpak IC was completely resolved.Vitacoenzyme,preparated by biological fermentation of soybeans residue,has been mainly used for chronic atrophic gastritis.The content determination item only specifies the content of VB2 in the current quality standard of Vitacoenzyme.It is reported that the main component of vitacoenzyme is vitamin B2,in addition,other types of vitamins(VB1、VB6、VB12 VC、VA、VD、VK、VE)and amino acids are also contained.Many studies have found that the chronic supplementation of antioxidants,such as vitamin B2,folic acid and vitamin A,has some effect on the prevention and treatment of gastric mucosal lesion.What’s more,the sampling inspection on vitacoenzyme tablets by the institute for drug control of baicheng city of jilin province in 2004 discovered that the nitrogen content had great distinction although VB2 content of vitacoenzyme tablets in the market accorded with the regulation.Obviously,stipulating of only VB2 content is not enough to reflect the inner quality of vitacoenzyme,known as multifunctional bioactive substances.However,the researches on the quality standard of vitacoenzyme only focus on the determination of the VB2 content currently.There is only one literature in 1985 that has measured the content of fat-soluble vitamins in vitacoenzyme.There is no literature reporting the specific content of amino acids in vitacoenzyme.This paper determined the contents of water-soluble vitamins,fat-soluble vitamins and amino acids in vitacoenzyme,respectively.However,no vitamin was found except for the VB2.For amino acids in vitacoenzyme,we developed the method to measure the free amino acids in vitacoenzyme by pre-column derivation RP-HPLC.What’s more,other low-molecular weight compounds in vitacoenzyme were detected by the general detector-evaporative light-scattering detector,and four unknown components were found in lipid-solubility extraction.Qualitative analysis showed that the four components were fatty acids:α-linolenic acid,inoleic acid,palmitic acid and oleic acid.Then,HPLC-ELSD method was developed to determinate the contents of these four fatty acids in vitacoenzyme simultaneously.To our knowledge,this is the first report about the specific content of amino acids in vitacoenzyme and about the existence of fatty acids in vitacoenzym.Vitacoenzym is rich in amino acids.And α-linolenic acid and linoleic acid are essential fatty acids for human,and that oleic acid is effective in protecting the gastric mucosa.The measurement of amino acids and fatty acids in vitacoenzyme can control the inner quality of vitacoenzyme more comprehensively,and is of great significance to further study the function of fatty acids in the process of pharmacological effects of vitacoenzym. |
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